What is CEDARS-SINAI MEDICAL CENTER's OSHA violation history?

CEDARS-SINAI MEDICAL CENTER has 19 OSHA inspections on record with 13 violations and $43,160 in total penalties.

How does CEDARS-SINAI MEDICAL CENTER's safety record compare to its industry?

CEDARS-SINAI MEDICAL CENTER operates in the general medical and surgical hospitals industry. The industry average Total Recordable Incident Rate (TRIR) is 5.1.

Has CEDARS-SINAI MEDICAL CENTER had any workplace fatalities?

Yes. Federal records show 3 fatality investigations involving CEDARS-SINAI MEDICAL CENTER.

Establishment profile

CEDARS-SINAI MEDICAL CENTER

8701 GRACIE ALLEN DR, LOS ANGELES, CA, 90048
622110 — General Medical and Surgical Hospitals

Download as PDF →

OSHA inspections

over 35 years

Violations

$43,160 in penalties

Penalties

$43,160

$3,320 avg

Violations across 3 federal agencies

Enforcement actions from multiple agencies may indicate systemic compliance issues across functions.

Accident investigations on record

3 fatalities · 1 hospitalizations

Summary

CEDARS-SINAI MEDICAL CENTER has accumulated 13 OSHA violations across 19 inspections over 35 years of recorded history, with $43,160 in total assessed penalties.

The establishment sits in the 94th percentile for violations within its industry-state peer group of 1,050 employers. Inspection frequency runs at the 99th percentile. The most recent enforcement activity was recorded 2 years ago.

Federal records were found in 3 of 15 sources. Sources without matching records returned empty for this establishment.

Agency coverage

CEDARS-SINAI MEDICAL CENTER appears in OSHA workplace safety, WHD wage enforcement, NLRB labor relations, and OFLC visa and labor certification (historical) records only. No matching records were found in MSHA mine safety, EPA environmental compliance, FMCSA motor carrier registration, SAM.gov federal debarment, CMS nursing home enforcement, UVA Corporate Prosecution Registry, CPSC product recalls, or NHTSA vehicle recalls.

OSHA workplace safety

Inspections

0.5 / yr · last 35 yrs

Violations

0.4 / yr

Penalties

$43,160

$3,320 avg / violation

31% serious69% other

Inspection trigger · complaint

14 of 19

Inspection trigger · accident

2 of 19

42% of inspections at this establishment produced violations, with 3 inspections producing serious-or-greater violations.

Most-cited OSHA standards

Top OSHA standards cited at this employer, ranked by citation count. Standards (CFR sections) cluster citations into safety themes -- machine guarding, lockout-tagout, hazard communication, fall protection, process safety, etc. A concentration on one or two sections reveals a pattern that individual citations don’t. 13 distinct standards shown · 13 citations in this view · $43,160 in penalties.

CFR section	Citations	Inspections	Total penalty	First cited	Last cited
3645 A	1	1	$18,000	Jan 2007	Jan 2007
5199(H)(6)(C)	1	1	$11,250	Jul 2021	Jul 2021
342(A)	1	1	$5,000	Jul 2021	Jul 2021
5199(D)	1	1	$5,000	Jul 2021	Jul 2021
5199(I)	1	1	$935	Feb 2023	Feb 2023
5193 D03 H2	1	1	$935	Apr 1999	Apr 1999
3210(A)	1	1	$600	Jul 2023	Jul 2023
29 CFR 4300.0007 B03	1	1	$450	Jul 2021	Jul 2021
3638 D	1	1	$375	Jan 2007	Jan 2007
3646 B	1	1	$335	Jan 2007	Jan 2007
3272 B	1	1	$280	Oct 1997	Oct 1997
29 CFR 1430.1 A02	1	1	—	Dec 1996	Dec 1996
3203 A02	1	1	—	May 1992	May 1992

Source: OSHA inspection citations (violation_detail). CFR section codes can be looked up at osha.gov/laws-regs for the formal standard text. Per-inspection detail and the specific violation descriptions are available by expanding individual inspections below.

Peer comparison

94th

Worse on violations than most other employers in NAICS 6221 within CA. Peer group: 1,050 employers. This establishment has 13 OSHA violations; peer median is 1.

Fewer violationsMore violations

Penalty percentile

99th

peer median: $420

Inspection frequency

99th

peer median: 1

Safety self-report (OSHA 300A)

No self-reported injury rates filed with OSHA's Injury Tracking Application for CEDARS-SINAI MEDICAL CENTER. Verify directly with OSHA Injury Tracking Application →

Industry benchmark

Industry avg TRIR

5.1

BLS SOII 2024

Industry avg DART

2.1

BLS SOII 2024

Self-reported TRIR

—

Not in OSHA ITA

BLS rates reflect industry-wide averages. Self-reported figures come from OSHA’s Injury Tracking Application; absence of self-reported data does not necessarily indicate non-compliance — many establishments fall below the ITA reporting threshold.

Inspection breakdown

Planned

Complaint

Accident

Referral

Complaint- and accident-triggered inspections are stronger risk signals than routine planned inspections.

OSHA severe injury reports

No severe injury reports (hospitalization, amputation, or loss of an eye) on file under 29 CFR 1904.39 for CEDARS-SINAI MEDICAL CENTER. Verify directly with Occupational Safety and Health Administration →

OSHA accident events

Accidents, fatalities, and catastrophes documented during OSHA inspections at this employer. Each entry links to the inspection that recorded it.

Date	Event	Injuries	Hospitalized	Fatalities
Mar 16, 2021	Infectious DiseaseFatality	3	—	3
Sep 9, 2006	FRACTURE,MAINTENANCE,OUTRIGGER,SCALP,LIGHTING FIXTURE,LACERATION,SKULL,PELVIS,RIB,CONCRETE	1	1	—

Source: OSHA accident investigations. Narratives are recorded by the inspecting officer and may be truncated.

Activity timeline

Data refreshed

Weekly

First OSHA inspection

—

Most recent activity

2 years ago

No federal enforcement activity has been recorded against this establishment in 2+ years. Most recent activity: 2 years ago. Data on this page is refreshed weekly.

Wage & Hour Division (WHD)

Cases

Back wages owed

Employees affected

Department of Labor Wage & Hour Division — minimum-wage, overtime, child-labor, FMLA, and prevailing-wage enforcement.

Wage and hour cases

Closed DOL Wage & Hour Division cases (FLSA, FMLA, H-2B, MSPA, and related statutes). Backwages reflect amounts the agency assessed; civil penalty (CMP) is a separate fine levied on top, where the statute provides for one (FLSA / H-1B / H-2A / MSPA / FMLA / EPPA / FLSA Child Labor; other acts have no CMP column in DOL’s data). The Statutes column lists which laws each case cited. 3 cases · $0 in backwages · 3 workers affected

Case period	Industry	Statutes	Violations	Workers	Backwages	Civil penalty
Feb 2019 – Jun 2019	General Medical and Surgical Hospitals	—	—	1	—	—
Mar 2012 – Apr 2012	General Medical and Surgical Hospitals	—	—	1	—	—
Sep 2008 – Oct 2009	General Medical and Surgical Hospitals	—	—	1	—	—

Source: DOL WHD enforcement database. Cases shown reflect those the agency has closed and made public. A violation count is the agency’s tally of cited violations (one violation can affect many workers); the workers column counts distinct employees the agency found to be affected.

Mine safety (MSHA)

No MSHA mine safety violations on file for CEDARS-SINAI MEDICAL CENTER. Verify directly with Mine Safety and Health Administration →

Labor relations (NLRB)

Company-level in CA — for CEDARS-SINAI MEDICAL CENTER, not this location alone

Total cases

Unfair labor practice

Representation (union)

National Labor Relations Board — unfair labor practice charges and union representation cases. The NLRB records cases at the company/regional level (no worksite address), so these are matched by company name and state and may span other CEDARS-SINAI MEDICAL CENTER locations in the same state.

NLRB cases

National Labor Relations Board cases involving this employer. Includes unfair labor practice (ULP) filings and representation election proceedings. NLRB enforcement is process-driven; no per-case monetary penalty is assessed (remedies are case-by-case backpay orders, posting requirements, election re-runs, etc.). 69 cases · 68 ULP · 1 representation

Case number	Type	Filed	Closed	Status	Region
31-CA-390510	Unfair labor practice	Jul 2026	—	Open	Region 31, Los Angeles, California
31-CA-372396	Unfair labor practice	Aug 2025	Sep 2025	Closed	Region 31, Los Angeles, California
31-CA-363783	Unfair labor practice	Apr 2025	—	Open	Region 31, Los Angeles, California
31-RC-361777	Representation election	Mar 2025	Apr 2025	Closed	Region 31, Los Angeles, California
31-CA-326787	Unfair labor practice	Sep 2023	Mar 2024	Closed	Region 31, Los Angeles, California
31-CA-310447	Unfair labor practice	Jan 2023	Aug 2023	Closed	Region 31, Los Angeles, California
31-CA-297819	Unfair labor practice	Jun 2022	Jul 2022	Closed	Region 31, Los Angeles, California
31-CA-297816	Unfair labor practice	Jun 2022	Aug 2022	Closed	Region 31, Los Angeles, California
31-CA-297695	Unfair labor practice	Jun 2022	Jul 2022	Closed	Region 31, Los Angeles, California
31-CA-297686	Unfair labor practice	Jun 2022	Sep 2025	Closed	Region 31, Los Angeles, California
31-CA-297684	Unfair labor practice	Jun 2022	Aug 2023	Closed	Region 31, Los Angeles, California
31-CA-297682	Unfair labor practice	Jun 2022	Feb 2024	Closed	Region 31, Los Angeles, California
31-CA-297676	Unfair labor practice	Jun 2022	Jul 2022	Closed	Region 31, Los Angeles, California
31-CA-296271	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
21-CA-296267	Unfair labor practice	May 2022	—	Open	Region 21, Los Angeles, California
31-CA-296004	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
31-CA-295994	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
31-CA-295634	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
31-CA-295633	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
31-CA-295632	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
31-CA-295613	Unfair labor practice	May 2022	Jun 2022	Closed	Region 31, Los Angeles, California
31-CA-294291	Unfair labor practice	Apr 2022	Oct 2023	Closed	Region 31, Los Angeles, California
31-CA-293205	Unfair labor practice	Mar 2022	Aug 2022	Closed	Region 31, Los Angeles, California
31-CA-292566	Unfair labor practice	Mar 2022	May 2022	Closed	Region 31, Los Angeles, California
31-CA-291740	Unfair labor practice	Mar 2022	Jan 2023	Closed	Region 31, Los Angeles, California
31-CA-274719	Unfair labor practice	Mar 2021	Apr 2021	Closed	Region 31, Los Angeles, California
31-CA-240894	Unfair labor practice	May 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-240270	Unfair labor practice	Apr 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-240248	Unfair labor practice	Apr 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-240136	Unfair labor practice	Apr 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-239729	Unfair labor practice	Apr 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-237479	Unfair labor practice	Mar 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-237416	Unfair labor practice	Mar 2019	Jun 2019	Closed	Region 31, Los Angeles, California
31-CA-220978	Unfair labor practice	May 2018	Aug 2018	Closed	Region 31, Los Angeles, California
31-CA-220843	Unfair labor practice	May 2018	Aug 2018	Closed	Region 31, Los Angeles, California
31-CA-207848	Unfair labor practice	Oct 2017	Mar 2018	Closed	Region 31, Los Angeles, California
31-CA-207674	Unfair labor practice	Oct 2017	Dec 2017	Closed	Region 31, Los Angeles, California
31-CA-204927	Unfair labor practice	Aug 2017	Mar 2018	Closed	Region 31, Los Angeles, California
31-CA-203462	Unfair labor practice	Jul 2017	Nov 2017	Closed	Region 31, Los Angeles, California
31-CA-202848	Unfair labor practice	Jul 2017	Nov 2018	Closed	Region 31, Los Angeles, California
31-CA-199862	Unfair labor practice	May 2017	Aug 2017	Closed	Region 31, Los Angeles, California
31-CA-199860	Unfair labor practice	May 2017	Aug 2017	Closed	Region 31, Los Angeles, California
31-CA-199680	Unfair labor practice	May 2017	Aug 2017	Closed	Region 31, Los Angeles, California
31-CA-199676	Unfair labor practice	May 2017	Jun 2017	Closed	Region 31, Los Angeles, California
31-CA-177177	Unfair labor practice	May 2016	Jun 2016	Closed	Region 31, Los Angeles, California
31-CA-172961	Unfair labor practice	Mar 2016	Jul 2016	Closed	Region 31, Los Angeles, California
31-CA-157491	Unfair labor practice	Aug 2015	Dec 2015	Closed	Region 31, Los Angeles, California
31-CA-147645	Unfair labor practice	Mar 2015	May 2015	Closed	Region 31, Los Angeles, California
31-CA-143038	Unfair labor practice	Dec 2014	Jun 2020	Closed	Region 31, Los Angeles, California
31-CA-141542	Unfair labor practice	Nov 2014	Dec 2014	Closed	Region 31, Los Angeles, California
31-CA-082472	Unfair labor practice	Jun 2012	Jul 2012	Closed	Region 31, Los Angeles, California
31-CA-029679	Unfair labor practice	Apr 2010	May 2010	Closed	Region 31, Los Angeles, California
31-CA-029622	Unfair labor practice	Mar 2010	Apr 2010	Closed	Region 31, Los Angeles, California
31-CA-029509	Unfair labor practice	Nov 2009	Dec 2009	Closed	Region 31, Los Angeles, California
31-CA-029508	Unfair labor practice	Nov 2009	Dec 2009	Closed	Region 31, Los Angeles, California
31-CA-029441	Unfair labor practice	Sep 2009	Nov 2009	Closed	Region 31, Los Angeles, California
31-CA-029440	Unfair labor practice	Sep 2009	Nov 2009	Closed	Region 31, Los Angeles, California
31-CA-029439	Unfair labor practice	Sep 2009	Nov 2009	Closed	Region 31, Los Angeles, California
31-CA-029178	Unfair labor practice	Apr 2009	May 2009	Closed	Region 31, Los Angeles, California
26-CA-023374	Unfair labor practice	Apr 2009	May 2009	Closed	Region 15, New Orleans, Louisiana
31-CA-028835	Unfair labor practice	Jul 2008	Sep 2008	Closed	Region 31, Los Angeles, California
31-CA-028797	Unfair labor practice	Jun 2008	Aug 2008	Closed	Region 31, Los Angeles, California
31-CA-028792	Unfair labor practice	Jun 2008	Aug 2008	Closed	Region 31, Los Angeles, California
31-CA-028592	Unfair labor practice	Nov 2007	Dec 2007	Closed	Region 31, Los Angeles, California
31-CA-028173	Unfair labor practice	Feb 2007	Oct 2007	Closed	Region 31, Los Angeles, California
31-CA-027430	Unfair labor practice	Jul 2005	Dec 2005	Closed	Region 31, Los Angeles, California
31-CA-027001	Unfair labor practice	Sep 2004	May 2005	Closed	Region 31, Los Angeles, California
31-CA-026973	Unfair labor practice	Aug 2004	Oct 2004	Closed	Region 31, Los Angeles, California
31-CA-026105	Unfair labor practice	Jan 2003	Oct 2004	Closed	Region 31, Los Angeles, California

Source: NLRB case files. Rows shown are those the agency has published. Region numbers (1–31) correspond to NLRB's geographic offices.

Visa & labor certification (OFLC) — historical

Total applications

152

Certified

151

Avg wage ratio

1.18x

E-3 AustralianH-1B

Office of Foreign Labor Certification — labor condition applications for H-1B, H-2A, H-2B visa programs. Wage ratio = offered / prevailing wage. Historical data only: DOL ended OFLC Performance Data Disclosure publication in 2026, so the figures above reflect filings through the last ingested cycle and are not being refreshed. Treat as a historical snapshot, not a current signal.

Environmental compliance (EPA)

No EPA inspections or formal enforcement actions on file for CEDARS-SINAI MEDICAL CENTER. Verify directly with Environmental Protection Agency →

EPA-registered facilities

Every EPA ECHO facility associated with this employer, sorted most-significant first. Each row links to EPA’s Detailed Facility Report for the source-of-truth record. Permits column lists active programs (Air = Clean Air Act, Water = Clean Water Act, RCRA = hazardous waste, TRI = Toxics Release Inventory reporting). 1 facility · 1 marked inactive.

Facility	Permits	Status	Inspections	Formal actions	Penalties	Last inspected	ECHO
CEDARS-SINAI MEDICAL CENTER 8700 BEVERLY · LOS ANGELES, CA, 90048	Water	—	0	0	—	—	View →

Source: EPA ECHO (Enforcement and Compliance History Online). Compliance status follows EPA’s own labels (“Sig Violation” = significant noncompliance; QNCR = quarters of noncompliance over the recent reporting window). Inactive facilities (struck through) retain historical enforcement records even after operations ceased.

Federal criminal prosecution record

No federal criminal prosecutions, plea agreements, or deferred-prosecution agreements on file for CEDARS-SINAI MEDICAL CENTER. Verify directly with UVA Corporate Prosecution Registry →

Federal contracts

This location

Obligated (5-yr)

$3.0M

Obligated (all-time)

$3.4M

Awards

Top agency

National Aeronautics and Space Administration

$2.9M

Top agencies by obligation (this location)

National Aeronautics and Space Administration$2.9M

Department of Veterans Affairs$255K

Department of Health and Human Services$166K

Department of Justice$41K

Department of Defense$229

Largest awards

Department of Health and Human Services
ASSESSMENT OF BIOMARKER GUIDED CNI SUBSTITUTION IN KIDNEY TRANSPLANTATION - CURRENT STANDARD OF CARE FOR KIDNEY TRANSPLANT (KTX) RECIPIENTS HAS ONLY MODESTLY IMPROVED LONG-TERM AGGREGATE GRAFT AND/OR PATIENT SURVIVAL, IDENTIFYING A CRUCIAL UNMET MEDICAL NEED. AS THE AT-RISK KTX POPULATION IS HETEROGENEOUS, THE CURRENTLY EMPLOYED AND RELATIVELY HOMOGENEOUS THERAPEUTIC APPROACH TO IMMUNOSUPPRESSION IN KTX IN THE US AND CANADA IS SUBOPTIMAL, AND RESULTS IN A SIGNIFICANT PROPORTION OF OVER- IMMUNOSUPPRESSED RECIPIENTS, MANY WITH TACROLIMUS-RELATED TOXICITIES. IN THIS U01 APPLICATION, CO-PIS HEEGER AND NICKERSON WILL BUILD UPON THEIR PAST, PRODUCTIVE COLLABORATIVE EFFORTS, THEIR ESTABLISHED MULTICENTER TRIAL CONSORTIUM AND INFRASTRUCTURE, AS WELL AS THEIR EXPERTISE IN BIOMARKERS AND MECHANISTIC STUDIES TO ADDRESS THIS UNMET NEED. THE OVERARCHING GOAL OF THE PROPOSED WORK IS TO DETERMINE THE UTILITY OF THE HLA-DR/DQ MOLECULAR MISMATCH (MMM) SCORE, AS A RISK STRATIFYING BIOMARKER IN KTX. WHILE RETROSPECTIVE STUDIES SHOWED STRONG CORRELATIONS BETWEEN THE HLA-DR/DQ MMM SCORE AND THE RISK OF DEVELOPING BIOPSY PROVEN ACUTE REJECTION (BPAR) AND/OR DONOR SPECIFIC ANTIBODIES (DSA), NO PROSPECTIVE STUDIES HAVE TESTED THE HLA MMM SCORE AS A RISK STRATIFYING BIOMARKER FOR IMMUNOLOGICAL KTX INJURY. NOR HAVE ANY STUDIES ATTEMPTED TO TEST WHETHER AND HOW THE HLA-DR/DQ MMM SCORE PERFORMS AS A PREDICTOR OF OUTCOME FOLLOWING A CHANGE IN TRANSPLANT IMMUNOSUPPRESSION. HEREIN, WE PROPOSE A MULTICENTER OBSERVATIONAL STUDY WITH A NESTED RANDOMIZED CONTROLLED (RCT) TRIAL TO ADDRESS THESE DEFICIENCIES. WE WILL PROSPECTIVELY TEST THE UTILITY OF THE HLA-DR/DQ MMM SCORE AS A PROGNOSTIC BIOMARKER OF PRIMARY ALLOIMMUNITY [T CELL MEDIATED REJECTION (TCMR), DSA, AND ANTIBODY MEDIATED REJECTION (ABMR)] IN KTX (AIM 1, OBSERVATIONAL STUDY OF 800 KTX). WE WILL ALSO TEST THE HYPOTHESIS THAT THE HLA-DR/DQ MMM SCORE IS A PREDICTIVE BIOMARKER THAT IDENTIFIES KTX RECIPIENTS WHO WILL TOLERATE SUBSTITUTING THE CALCINEURIN INHIBITOR WITH SELF-ADMINISTERED, SUBCUTANEOUS ABATACEPT (COSTIMULATORY BLOCKADE), WITHOUT AN UNACCEPTABLE INCREASED RISK OF BPAR, WHILE REDUCING THE MORBIDITY OF CNI OFF-TARGET EFFECTS (300 KTX, NESTED RCT WITH A NON-INFERIORITY ENDPOINT, AIM 2). ACCOMPANYING MECHANISTIC STUDIES (AIM 3) WILL PROVIDE NOVEL IMMUNOLOGICAL AND MOLECULAR INSIGHTS THAT WILL ALSO AID IN INTERPRETING GRAFT AND RECIPIENT OUTCOMES OF THE TRIAL. IF SUCCESSFUL, THE WORK WILL PROVIDE CRUCIAL INFORMATION CAPABLE OF POSITIVELY, AND DIRECTLY AFFECTING CLINICAL CARE. THE RESULTS FROM THE PROPOSED WORK ALSO HAVE THE POTENTIAL TO INFLUENCE POSITIVELY THE DESIGN OF FUTURE RCTS BY PROVIDING AN HLA-DR/DQ MMM SCORE-BASED STRATIFICATION OR ENRICHMENT STRATEGY FOR ENROLLING SUBJECTS INTO TRIALS MOST LIKELY TO BE INFORMATIVE FOR THE PROPOSED STUDY AGENT-- THEREBY INCREASING LIKELIHOOD OF TRIAL SUCCESS IN THE SHORTEST POSSIBLE TIME.
assistance · Last action 2026-05-12
$12,253,237
Department of Health and Human Services
MAPPING THE GENES FOR IBD BY ADMIXTURE LINKAGE DISEQUILIBRIUM IN PUERTO RICANS
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$9,562,512
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DETERMINANTS OF LIVER METASTASIS
assistance · Last action 2026-05-01
$9,538,426
Department of Health and Human Services
THE MICROVASCULAR AGING AND EICOSANOIDS - WOMEN'S EVALUATION OF SYSTEMIC AGING TENACITY (MAE-WEST) ("YOU ARE NEVER TOO OLD TO BECOME YOUNGER!") SPECIALIZED CENTER FOR RESEARCH EXCELLENCE (SCORE)
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$8,744,039
Department of Health and Human Services
MECHANISMS OF EPITHELIAL ALTERATIONS IN DIABETIC CORNEA
assistance · Last action 2025-09-19
$8,513,462
Department of Health and Human Services
CSMC SPECIAL PATHOGENS REGIONAL EMERGING SPECIAL PATHOGEN TREATMENT CENTER COOPERATIVE AGREEMENT YEAR 1 - THE RECIPIENT, CEDARS-SINAI MEDICAL CENTER (CSMC), SUPPORTS THIS FIVE-YEAR REGIONAL EMERGING SPECIAL PATHOGEN TREATMENT CENTER COOPERATIVE AGREEMENT IN COLLABORATION WITH FEDERAL, STATE, AND LOCAL STAKEHOLDERS RELATED TO SPECIAL PATHOGENS (SP) PREPAREDNESS, RESPONSE, AND TREATMENT. THE GOAL OF THE CSMC SP PROGRAM IS TO CONTINUE TO SUSTAIN AND ADVANCE COMPREHENSIVE, COORDINATED RESPONSE AND TREATMENT FOR SP PATIENTS WITHIN HEALTH AND HUMAN SERVICES (HHS) REGION 9 (R9) AND FURTHER ABROAD, AS NEEDED. THE APPROACH IS TO EXPAND PREPAREDNESS EFFORTS AND ADVANCE TREATMENT AND RESEARCH CAPABILITIES WITHIN HHS R9 AS PART OF THE NATIONAL SPECIAL PATHOGENS PREPAREDNESS SYSTEM (NSPS). THE OBJECTIVES ARE: 1) TO MAINTAIN THE ABILITY TO BE READY TO ACCEPT AND TREAT SP PATIENTS USING STANDARDIZED PROTOCOLS; 2) ENHANCE CAPABILITY AND CAPACITY TO PARTICIPATE IN SP RESEARCH; 3) TRAIN AND MAINTAIN A WORKFORCE CAPABLE OF PROVIDING SP PATIENT CARE; 4) SUPPORT CONTINUED PLANNING FOR DEVELOPMENT OF A REGIONAL NETWORK FOR SP PATIENT CARE DELIVERY; 5) MAINTAIN COORDINATION PLANS TO ENABLE REGIONAL PARTNERS TO HAVE THE CAPABILITIES TO CARE FOR SP PATIENTS; 6) ENGAGE IN EVALUATION ACTIVITIES AND ASSESSMENTS TO ENSURE READINESS TO ACCEPT AND TREAT A SP PATIENT AND; 7) PROVIDE EVALUATION AND PERFORMANCE MEASUREMENT OF ACTIVITIES. THE OUTCOMES ARE TO PROMOTE QUALITY, COORDINATED SP CARE THAT IS EQUALLY ACCESSIBLE TO ALL PATIENTS THROUGH THE DEVELOPMENT OF A SPECIALIZED WORKFORCE, ENHANCEMENT OF RESEARCH CAPABILITIES, AND IMPROVED COORDINATION OF CARE ACROSS HHS R9. THE PRODUCTS FROM THIS AGREEMENT WILL BE: 1) A FINAL COMPREHENSIVE SP PROGRAM REPORT INCLUDING PEER-EVALUATED ASSESSMENTS OF PREVIOUSLY DESCRIBED OBJECTIVES; 2) PUBLISHED ARTICLES; 3) A WEBSITE; AND 4) WORKFORCE ENHANCING TRAINING OPPORTUNITIES.
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$8,046,152
Department of Health and Human Services
NEURONAL MECHANISMS OF HUMAN EPISODIC MEMORY
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$7,798,646
Department of Health and Human Services
1/24 HEALTHY BRAIN AND CHILD DEVELOPMENT NATIONAL CONSORTIUM - PROJECT SUMMARY/ABSTRACT NEURODEVELOPMENTAL PROCESSES ARE SHAPED BY DYNAMIC INTERACTIONS BETWEEN GENES AND ENVIRONMENTS. MALADAPTIVE EXPERIENCES EARLY IN LIFE CAN ALTER DEVELOPMENTAL TRAJECTORIES, LEADING TO HARMFUL AND ENDURING DEVELOPMENTAL SEQUELAE. PRE- AND POSTNATAL HAZARDS INCLUDE MATERNAL SUBSTANCE EXPOSURE, TOXICANT EXPOSURES IN PREGNANCY AND EARLY LIFE, MATERNAL HEALTH CONDITIONS, PARENTAL PSYCHOPATHOLOGY, MALTREATMENT, STRUCTURAL RACISM, AND EXCESSIVE STRESS. TO ELUCIDATE HOW VARIOUS ENVIRONMENTAL HAZARDS IMPACT CHILD DEVELOPMENT, IT IS IMPERATIVE THAT A NORMATIVE TEMPLATE OF DEVELOPMENTAL TRAJECTORIES OVER THE FIRST 10 YEARS OF LIFE BE ESTABLISHED BASED ON A SUFFICIENTLY LARGE AND DEMOGRAPHICALLY DIVERSE SAMPLE OF THE US POPULATION. TO ACCOMPLISH THIS, THE HEALTHY BRAIN AND CHILD DEVELOPMENT NATIONAL CONSORTIUM (HBCD-NC) HAS BEEN FORMED TO DEPLOY A HARMONIZED, OPTIMIZED, AND INNOVATIVE SET OF NEUROIMAGING (MRI, EEG) MEASURES COMPLEMENTED BY AN EXTENSIVE BATTERY OF BEHAVIORAL, PHYSIOLOGICAL, AND PSYCHOLOGICAL TOOLS, AND BIOSPECIMENS TO UNDERSTAND NEURODEVELOPMENTAL TRAJECTORIES IN A SAMPLE OF 7,500 MOTHERS AND INFANTS ENROLLED AT 24 SITES ACROSS THE UNITED STATES (US). THE HBCD-NC WILL CARRY OUT A COMMON RESEARCH PROTOCOL UNDER DIRECTION OF THE HBCD- NC ADMINISTRATIVE CORE (HCAC) AND WILL ASSEMBLE AND DISTRIBUTE A COMPREHENSIVE AND WELL-CURATED RESEARCH DATASET TO THE SCIENTIFIC COMMUNITY AT LARGE UNDER THE DIRECTION OF THE HBCD-NC DATA COORDINATING CENTER (HDCC). THE OVERARCHING GOAL OF THE HBCD-NC IS TO CREATE A COMPREHENSIVE, HARMONIZED, AND HIGH- DIMENSIONAL DATASET THAT WILL CHARACTERIZE TYPICAL NEURODEVELOPMENTAL TRAJECTORIES IN US CHILDREN AND THAT WILL ASSESS HOW BIOLOGICAL AND ENVIRONMENTAL EXPOSURES AFFECT THOSE TRAJECTORIES. A SPECIAL EMPHASIS WILL BE PLACED ON UNDERSTANDING THE IMPACT OF PRE- AND POSTNATAL EXPOSURE TO OPIOIDS, MARIJUANA, ALCOHOL, TOBACCO AND/OR OTHER SUBSTANCES. TO ADDRESS THESE BROAD OBJECTIVES, THE SAMPLE OF WOMEN ENROLLED WILL INCLUDE: 1) A RACIALLY, ETHNICALLY, AND SOCIOECONOMICALLY DIVERSE COHORT THAT IS REPRESENTATIVE OF THE US POPULATION; 2) PREGNANT WOMAN WITH USE OF TARGETED SUBSTANCES (OPIOIDS, MARIJUANA, ALCOHOL, TOBACCO); AND 3) DEMOGRAPHICALLY AND BEHAVIORALLY SIMILAR WOMEN WITHOUT SUBSTANCE USE IN PREGNANCY TO ENABLE VALID CAUSAL INFERENCES. IN ADDITION, THE HBCD-NC WILL IDENTIFY KEY DEVELOPMENTAL WINDOWS DURING WHICH BOTH HARMFUL AND PROTECTIVE ENVIRONMENTS HAVE THE MOST INFLUENCE ON LATER NEURODEVELOPMENTAL OUTCOMES. THE LARGE, MULTI- MODAL, LONGITUDINAL, AND GENERALIZABLE DATASET THAT WILL BE PRODUCED FOR THE FIRST TIME BY THIS STUDY WILL PROVIDE NOVEL INSIGHTS INTO CHILD DEVELOPMENT USING STATE-OF-THE-ART METHODS. THE HBCD-NC STUDY WILL INFORM PUBLIC POLICY TO IMPROVE THE HEALTH AND DEVELOPMENT OF CHILDREN ACROSS THE NATION.
assistance · Last action 2026-05-07
$6,945,966
Department of Health and Human Services
ARTIFICIAL INTELLIGENCE STRATEGIES FOR ALZHEIMER'S DISEASE RESEARCH - ALZHEIMER'S DISEASE (AD) IS A COMMON DISEASE THAT IS PARTLY DUE TO PROTEIN MISFOLDING AND AGGREGATION. RESEARCH ON AD IS A NATIONAL PRIORITY WITH 5.5 MILLION AMERICANS AFFECTED AT AN ANNUAL COST OF MORE THAN $250 BILLION AND NO AVAILABLE CURE. THIS IS DESPITE HEAVY INVESTMENTS IN THE COLLECTION OF DIVERSE CLINICAL AND BIOLOGICAL DATA IN EXPERIMENTAL AND POPULATION-BASED STUDIES. ARTIFICIAL INTELLIGENCE (AI) AND MACHINE LEARNING HAVE THE POTENTIAL TO REVEAL PATTERNS IN CLINICAL AND MULTI-SOURCE LARGE-SCALE ALZHEIMER’S DATA THAT HAVE NOT BEEN FOUND USING STANDARD APPROACHES. WE PROPOSE HERE A COMPREHENSIVE BIOMEDICAL COMPUTING AND HEALTH INFORMATICS RESEARCH PROJECT TO DEVELOP AND APPLY CUTTING-EDGE AI ALGORITHMS AND BIOMEDICAL SOFTWARE FOR THE ANALYSIS OF LARGE- SCALE AD DATA. AT THE HEART OF THIS PROPOSED INFORMATICS PROGRAM IS THE PENNAI METHOD AND SOFTWARE FOR AUTOMATING MACHINE LEARNING THROUGH AN AI ALGORITHM THAT CAN LEARN FROM PRIOR ANALYSES. THIS APPROACH TAKES THE GUESSWORK OUT OF PICKING THE RIGHT MACHINE LEARNING ALGORITHMS AND PARAMETER SETTINGS THUS MAKING THIS COMPUTING TECHNOLOGY ACCESSIBLE TO EVERYONE. SPECIFICALLY, WE WILL DEVELOP THREE NOVEL INFORMATICS METHODS TO TAILOR PENNAI TO THE ANALYSIS OF AD DATA. FIRST, WE WILL DEVELOP A MULTI-MODAL INTERACTION (M2I) FEATURE SELECTION ALGORITHM FOR IDENTIFYING GENETIC INTERACTIONS THAT ARE PREDICTIVE OF AD (AIM 1). SECOND, WE WILL DEVELOP A KNOWLEDGE-DRIVEN MULTI-OMICS INTEGRATION (KMI) ALGORITHM FOR COMBINING OMICS FEATURES FOR AI ANALYSIS OF AD (AIM 2). THIRD, WE WILL DEVELOP A MULTIDIMENSIONAL BRAIN IMAGING OMICS (MBIO) INTEGRATION FRAMEWORK FOR THE JOINT ANALYSIS OF MULTI-SOURCE LARGE-SCALE DATA FOR PREDICTING AD. FINALLY, WE WILL INTEGRATE ALL THREE BIOMEDICAL INFORMATICS METHODS INTO OUR OPEN-SOURCE PENNAI SOFTWARE PACKAGE AND APPLY IT TO TWO LARGE POPULATION-BASED STUDIES OF AD. WE EXPECT PENNAI WILL REVEAL NEW BIOMARKERS FOR AD THAT WILL OPEN THE DOOR FOR BETTER TREATMENTS AND CLINICAL DECISION SUPPORT.
assistance · Last action 2025-09-10
$6,749,268
Department of Health and Human Services
SEX, CHROMOSOMES, AND IMMUNITY IN BLADDER CANCER - OVERALL – SUMMARY BLADDER CANCER (BC) IS 3-5 TIMES MORE COMMON IN MEN EVEN WHEN ADJUSTED FOR ENVIRONMENTAL FACTORS SUCH AS SMOKING, THE PRIMARY RISK FACTOR FOR THIS DISEASE. THE GOAL OF THIS PROGRAM PROJECT GRANT (PPG) IS TO ADVANCE OUR KNOWLEDGE OF “SEX AS A BIOLOGICAL VARIABLE (SABV)” IN BC, WITH THE ULTIMATE OBJECTIVE OF IMPROVING PATIENT OUTCOMES BY DISCOVERING SEX-SPECIFIC DRIVERS THAT CAN BE TARGETED THERAPEUTICALLY. BENCHMARKS OF SUCCESS AND IMPACT FOR THE PROGRAM INCLUDE IDENTIFICATION OF KEY IMMUNOLOGICAL, HORMONAL, CHROMOSOMAL, GENETIC, AND EPIGENETIC PATHWAYS RESPONSIBLE FOR SEX-DRIVEN BIOLOGICAL PHENOTYPES IN BC TO INSPIRE THE DESIGN OF A NOVEL LINE OF BC THERAPEUTICS BASED ON EACH PATIENT’S BIOLOGICAL SEX. TO THIS END, THE PPG WILL UNITE THREE LEADING LABORATORIES IN THEIR RESPECTIVE FIELDS, EACH TACKLING THE PROBLEM OF SABV FROM A UNIQUE AND COMPLEMENTARY STANDPOINT OF EXPERTISE: IMMUNOLOGY, CANCER BIOLOGY/FUNCTIONAL GENOMICS, AND EPIGENETICS. THESE THREE RESEARCH GROUPS, SUPPORTED BY CEDARS-SINAI MEDICAL CENTER CANCER CENTER AND THE OHIO STATE UNIVERSITY COMPREHENSIVE CANCER CENTER, HAVE A PROVEN HISTORY OF COLLABORATION, WITH NINE JOINT PUBLICATIONS SINCE 2017 AND MULTIPLE CO- AUTHORED PAPERS IN THE PIPELINE. PROJECT 1 AIMS TO UNCOVER THE IMMUNOLOGICAL BASIS OF SEX DIFFERENCES IN BC, TAKING ADVANTAGE OF A RECENT DISCOVERY IN T CELL INTRINSIC ANDROGEN RECEPTOR SIGNALING IN CD8+ T CELL EXHAUSTION. PROJECT 2 WILL FOCUS ON THE ROLE OF THE Y CHROMOSOME AND THE Y-LINED EPIGENETIC REGULATORS IN DRIVING BC PROGRESSION AND RESISTANCE TO IMMUNE CHECKPOINT BLOCKADE (ICB); AND PROJECT 3 WILL INVESTIGATE TUMOR SUPPRESSING ACTIVITY OF THE X CHROMOSOME-LINKED EPIGENETIC REGULATOR AND THE ROLES OF ANDROGEN AND ESTROGEN- DEPENDENT SEX HORMONE PATHWAYS, AIMING TO ELUCIDATE THE EPIGENETIC BASIS OF SEX DIFFERENCES IN BC. ALL THREE PROJECTS WILL BE SUPPORTED BY AN ADMINISTRATIVE CORE (ADMIN CORE) AND TWO SHARED RESOURCE CORES – THE SYSTEMS PATHOLOGY CORE (CORE 1) AND THE DATA SCIENCE CORE (CORE 2). ADMIN CORE WILL MANAGE AND SUPPORT THE ENTIRE PROGRAM BY OFFERING ADMINISTRATIVE AND FISCAL MANAGEMENT SUPPORT AND FACILITATING COMMUNICATION AND SCIENTIFIC INTERACTIONS. CORE 1 WILL PROVIDE STATE-OF-THE-ART DIGITAL PATHOLOGY SERVICES, AUTOMATED AND PERSONALIZED IMAGE ANALYSES, AND MULTIPARAMETER IMMUNE MONITORING. CORE 2 WILL PROVIDE UNIFIED DATA PROCESSING, ANALYTICAL PIPELINES, DATA INTEGRATION, DATA REPOSITORY, AND STATISTICAL CONSULTATION. BECAUSE MALE PREVALENCE IN CANCER INCIDENCE AND MORTALITY IS OBSERVED ACROSS MANY OTHER CANCER TYPES, OUR SCIENTIFIC FINDINGS WILL LIKELY HAVE BROAD IMPLICATIONS IN CANCER MEDICINE FAR BEYOND BC.
assistance · Last action 2026-04-15
$6,555,140
Department of Health and Human Services
PRE-DETERMINE: ADVANCING SUDDEN ARRHYTHMIC DEATH PREDICTION IN CORONARY ARTERY DISEASE IN THE ABSENCE OF SEVERE SYSTOLIC DYSFUNCTION - SUDDEN AND/OR ARRHYTHMIC DEATH (SAD), WHICH TYPICALLY RESULTS FROM LETHAL VENTRICULAR ARRHYTHMIAS (VENTRICULAR TACHYCARDIA AND VENTRICULAR FIBRILLATION, VT/VF) IN THE SETTING OF CORONARY HEART DISEASE (CHD), AFFLICTS AN ESTIMATED 310,000 PERSONS ANNUALLY IN THE UNITED STATES. REDUCTIONS IN SAD HAVE CONTINUED TO LAG THOSE OBSERVED FOR OTHER CORONARY HEART DISEASE (CHD) OUTCOMES DESPITE ADVANCES IN RESUSCITATION THERAPIES AND THE USE OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS (ICDS). CURRENT APPROACHES TO SAD PREVENTION REMAIN CENTERED ON PLACING ICDS IN PATIENTS WITH LEFT VENTRICULAR EJECTION FRACTION (LVEF) <30-35% – EVEN THOUGH THE MAJORITY OF SAD OCCURS IN THE SETTING OF LVEF >30-35%. IN EFFECT, THE PROPORTIONATELY LARGER SEGMENT OF THE AT-RISK POPULATION HAS BEEN UNDERSTUDIED AND THUS UNDERTREATED. DESPITE THIS UNMET NEED, THERE REMAIN VERY FEW, IF ANY, PROSPECTIVE STUDIES EXAMINING SAD RISK PREDICTION IN INDIVIDUALS WITH CHD AND LVEF >30-35% OVER A LONG ENOUGH TIME HORIZON WHERE ICD THERAPY MIGHT BE COST-EFFECTIVE. FOR THIS VERY REASON, THE PRE- DETERMINE COHORT STUDY WAS INTENTIONALLY DESIGNED TO ADDRESS THIS SCIENTIFIC GAP AND PROSPECTIVELY STUDY CLINICALLY RELEVANT APPROACHES TO SAD RISK PREDICTION IN CHD PATIENTS WITH LVEF >30-35%. IN THIS APPLICATION, WE PROPOSE TO LEVERAGE THE ORIGINALLY NHLBI-FUNDED BASE COHORT RESOURCE TO CONTINUE ADJUDICATION OF ACCRUING SAD AND VT/VF EVENTS, IN ADDITION TO COMPETING CAUSES OF DEATH, TO ATTAIN 10+ YEARS OF ENDPOINT ADJUDICATION TO ENABLE THE DEVELOPMENT AND VALIDATION OF MULTI-MARKER SAD RISK PREDICTION MODELS BASED ON COMBINATIONS OF MULTI-DIMENSIONAL CLINICAL, ECG, IMAGING, BIOMARKER, AND GENETIC DATA GENERATED IN THIS UNIQUE MULTICENTER COHORT OF 5761 CHD PATIENTS. WE WILL ALSO LEVERAGE THE BASE COHORT TO INTERROGATE NOVEL FATTY ACID DERIVED EICOSANOIDS AND PUTATIVE ARRHYTHMIA MODULATING PROTEOMIC ANALYTES IN RELATION TO RISK FOR SAD AND COMPETING CAUSES OF MORTALITY IN PATIENTS WITH CHD. NOVEL METHODS OF COMPETING RISK ANALYSES WILL BE USED TO INTEGRATE ABSOLUTE AND PROPORTIONAL SAD RISK INTO SAD RISK PREDICTION MODELS AND TO ELUCIDATE SEPARATE ASSOCIATIONS BETWEEN SAD VS. NON-SAD CAUSES OF DEATH. MACHINE LEARNING APPROACHES WILL BE APPLIED TO UNCOVER INTER-RELATIONS AND LATENT FEATURES FROM MULTI-MODALITY DATA NOT EASILY DETECTED BY CONVENTIONAL MODELS. AN OVERARCHING GOAL OF OUR WORK IS TO ACCURATELY IDENTIFY THOSE INDIVIDUAL SUBSETS OF THE BROADER POPULATION WHO HAVE SUFFICIENTLY HIGH ABSOLUTE AND PROPORTIONAL RISK FOR SAD THAT THEY WARRANT INCLUSION IN RANDOMIZED TRIALS OF PRIMARY PREVENTION ICD THERAPY. THE AIMS OF THE CURRENT PROPOSAL ALSO OFFER NEW OPPORTUNITIES TO IDENTIFY POTENTIAL MECHANISTIC PATHWAYS UNDERLYING THE GENESIS OF LETHAL VENTRICULAR ARRHYTHMIAS THAT COULD SERVE AS NOVEL TARGETS FOR SAD PREVENTION – EXTENDING BEYOND ICD PLACEMENT – IN PATIENTS WITH CHD AND POSSIBLY EVEN IN THE GENERAL POPULATION WHEREIN CHD UNDERLIES MOST SAD EVENTS. THE CONTINUATION AND EXPANSION OF THE PRE-DETERMINE STUDY WILL PROVIDE THE SCIENTIFIC FIELD WITH A ONE-OF-A KIND RESOURCE FOR INVESTIGATORS AND TRAINEES COLLABORATING TOWARD THE COMMON GOAL OF REDUCING THE BURDEN OF SAD.
assistance · Last action 2026-04-22
$6,041,692
Department of Health and Human Services
DIAGNOSIS OF DISCOGENIC LOW BACK PAIN USING PH LEVEL-DEPENDENT MRI
assistance · Last action 2025-08-15
$5,229,490
Department of Health and Human Services
MOLECULAR REGULATION OF PROGRESSIVE PULMONARY FIBROSIS
assistance · Last action 2025-07-17
$5,068,279
Department of Health and Human Services
KRONOSRX: SENDING PATIENT AVATARS TO THE FUTURE TO TRANSFORM DRUG SAFETY PREDICTION
assistance · Last action 2026-01-16
$5,054,235
Department of Health and Human Services
TRAINING IN ADVANCED HEART DISEASE RESEARCH
assistance · Last action 2025-09-05
$5,025,435
Department of Health and Human Services
PATIENT-SPECIFIC OUTCOME PREDICTION FROM CARDIOVASCULAR MULTIMODALITY IMAGING BY ARTIFICIAL INTELLIGENCE - PROJECT SUMMARY CORONARY ARTERY DISEASE (CAD) REMAINS A MAJOR PUBLIC HEALTH CONCERN WITH A HIGH PREVALENCE IN THE US POPULATION. FUNCTIONAL, MOLECULAR, AND STRUCTURAL IMAGING OFFER A UNIQUE OPPORTUNITY TO UNDERSTAND THE PATHOPHYSIOLOGY OF CAD, ESPECIALLY IN HIGH-RISK GROUPS SUCH AS PATIENTS WITH OBESITY, DIABETES, AND CHRONIC KIDNEY DISEASE (CARDIOMETABOLIC DISEASE). CAD EVALUATION BY IMAGING IS BASED ON MODALITIES THAT ASSESS (1) MYOCARDIAL ISCHEMIA AND MYOCARDIAL BLOOD FLOW (2) ANATOMIC BURDEN OF ATHEROSCLEROSIS, AND (3) DISEASE ACTIVITY USING NOVEL TECHNIQUES. HOWEVER, PHYSICIANS ARE NOT YET ABLE TO USE THESE DATA OPTIMALLY TO IDENTIFY PATIENTS AT HIGHEST RISK OF ADVERSE EVENTS—DUE TO TECHNICAL COMPLEXITY OF ADVANCED MULTIVARIABLE DATA, AND LACK OF AUTOMATION AND INTEGRATIVE TOOLS. WHILE POSITRON EMISSION TOMOGRAPHY (PET) CAN MEASURE MYOCARDIAL BLOOD FLOW, AND DEPICT HIGH-RISK PLAQUE IN THE ARTERIES AND CT CAN RELIABLY DETECT CORONARY ARTERY CALCIUM —AN UNEQUIVOCAL MARKER FOR ATHEROSCLEROTIC DISEASE– PHYSICIANS ARE NOT ABLE TO COMBINE THESE DATA EFFECTIVELY TO IDENTIFY PATIENTS AT HIGHEST RISK OF ADVERSE EVENTS, DUE TO COMPLEXITY AND LACK OF AUTOMATION. CRITICALLY, THERE IS AN UNMET NEED FOR EFFICIENT INTEGRATION OF DIVERSE IMAGING AND CLINICAL DATA BY A ROBUST, AUTOMATED CLINICAL TOOL AFTER NON-INVASIVE IMAGING. HIGHLY EFFICIENT ARTIFICIAL INTELLIGENCE (AI) METHODS ARE REVOLUTIONIZING IMAGE ANALYSIS AND COULD IMPROVE CAD DETECTION AND MANAGEMENT. THE OVERALL VISION FOR THE RESEARCH PROGRAM IS TO FURTHER THE CLINICAL UTILITY OF PET/CT IN DETECTING HIGH-RISK CAD AND GUIDING SUBSEQUENT MANAGEMENT BY AUTOMATION AND INTEGRATING ALL IMAGE AND CLINICAL DATA WITH STATE-OF-THE-ART AI. WE WILL ESTABLISH A LARGE MULTICENTER PET AND CT IMAGING REGISTRY AND WITH IMAGE-BASED AI, AUTOMATE ANALYSIS AND QUALITY CONTROL FOR ROBUST ANALYSIS EVEN AT LESS EXPERIENCED CENTERS, AND DEVELOP DECISION SUPPORT TOOLS UTILIZING COLLECTIVELY ALL AVAILABLE PET/CT IMAGES AND CLINICAL INFORMATION (BEYOND WHAT IS POSSIBLE BY SUBJECTIVE VISUAL ANALYSIS AND MENTAL INTEGRATION). WE WILL DEVELOP DIRECT INTERPRETATION OF IMAGES BY AI, AND PATIENT-SPECIFIC EXPLANATION OF THE AI FINDINGS TO THE PHYSICIAN. PRECISE QUANTITATIVE RESULTS WILL BE PRESENTED TO CLINICIANS (AND PATIENTS) IN EASY TO UNDERSTAND TERMS (E.G., % RISK PER YEAR OR AS THE RELATIVE RISK OF ONE THERAPY COMPARED TO THE ALTERNATIVE) FOR A SPECIFIC PATIENT. THIS WORK WILL ALLOW ACCURATE IDENTIFICATION OF PATIENTS WITH HIGH-RISK DISEASE WHO CAN BENEFIT TREATMENT FROM ADVANCED THERAPIES AND ENABLE PRECISE PATIENT-SPECIFIC RISK ESTIMATES AND TREATMENT RECOMMENDATIONS IN CHALLENGING CLINICAL SCENARIOS—IN CAD WITH CARDIOMETABOLIC DISEASE AND ADVANCED HIGH- RISK DISEASE.
assistance · Last action 2026-06-19
$5,023,391
Department of Health and Human Services
PATHOPHYSIOLOGY, EPIDEMIOLOGY, AND PREVENTION OF PANCREATOGENIC DIABETES
assistance · Last action 2026-03-26
$4,975,345
Department of Health and Human Services
ALZHEIMER'S DISEASE HALLMARK PATHOLOGY AND ASSOCIATED INFLAMMATION IN THE RETINA
assistance · Last action 2026-06-18
$4,855,141
Department of Health and Human Services
PREDICTING PANCREATIC DUCTAL ADENOCARCINOMA (PDAC) THROUGH ARTIFICIAL INTELLIGENCE ANALYSIS OF PRE-DIAGNOSTIC CT IMAGES - THE OBJECTIVE OF THE PROPOSED PROJECT IS TO DEVELOP A PANCREATIC DUCTAL ADENOCARCINOMA (PDAC) PREDICTION MODEL TO IDENTIFY INDIVIDUALS WHO HAVE HIGH RISK FOR PDAC IN THE NEXT 3 YEARS THROUGH ARTIFICIAL INTELLIGENCE (AI) ANALYSIS OF PRE-DIAGNOSTIC CT IMAGES AND NON-IMAGING FACTORS. PDAC IS THE FOURTH LEADING CAUSE OF CANCER- RELATED DEATHS IN BOTH MEN AND WOMEN IN THE UNITED STATES DESPITE ITS LOW INCIDENCE RATE. THE 5-YEAR SURVIVAL RATE FOR ALL STAGES OF PDAC IS 10% BUT CAN BE AS HIGH AS 50% WITH EARLY-STAGE DIAGNOSIS. THEREFORE, IDENTIFICATION OF INDIVIDUALS AT HIGH RISK FOR PDAC HAS HIGH CLINICAL SIGNIFICANCE AS FOLLOW-UP IMAGING EXAMINATIONS OR BIOPSY MAY ASSIST IN EARLY DETECTION AND ALLOW SURGICAL INTERVENTION WHILE THE TUMORS ARE STILL RESECTABLE. HOWEVER, PDAC PREDICTION IS DIFFICULT DUE TO THE LACK OF RELIABLE SCREENING TOOLS, THE ABSENCE OF SENSITIVE AND SPECIFIC SYMPTOMS AND BIOMARKERS, AND LOW PREVALENCE. ABDOMINAL PAIN IS THE SINGLE MOST COMMON REASON THAT AMERICANS VISIT THE EMERGENCY ROOM (ER), WHERE AN ABDOMINAL COMPUTED TOMOGRAPHY (CT) SCAN IS USUALLY PERFORMED. EVEN THOUGH MOST SCANS DON’T SHOW ANY SIGNS OF CANCER VISIBLE TO THE NAKED EYES OF RADIOLOGISTS, SOME SUBJECTS EVENTUALLY DEVELOP PDAC IN THE NEXT FEW YEARS. THESE PRE-DIAGNOSTIC CT IMAGES PROVIDE CRITICAL MORPHOLOGICAL INFORMATION ASSOCIATED WITH BIOLOGICAL CHANGES AT THE PRE-CANCER OR EARLY CANCER STAGE, WHICH CAN BE EXTRACTED USING AI TO PREDICT PDAC RISK. THEREFORE, THE OBJECTIVE OF THE PROPOSED PROJECT IS TO UNCOVER UNIQUE FEATURES IN PRE-DIAGNOSTIC IMAGES USING AI AND DEVELOP PDAC PREDICTION MODEL BASED ON THESE FEATURES. NON-IMAGING FACTORS SUCH AS DEMOGRAPHIC, EPIDEMIOLOGIC, AND ANTHROPOMETRIC FACTORS, CLINICAL COMORBIDITIES, AND LABORATORY TESTS WILL BE INCLUDED IN THE MODEL TO IMPROVE THE PREDICTION ACCURACY. THE PRIMARY HYPOTHESES ARE A) AI ALLOWS EXTRACTION OF UNIQUE IMAGE FEATURES IN PRE-DIAGNOSTIC CT IMAGES ASSOCIATED WITH PRE-CANCER OR EARLY CANCER BIOLOGICAL CHANGES THAT ARE INVISIBLE TO NAKED EYES AND B) THE COMBINATION OF PRE-DIAGNOSTIC IMAGE FEATURES AND NON- IMAGING FACTORS IMPROVES THE ACCURACY OF PDAC RISK STRATIFICATION AND PREDICTION OVER THAT USING CONVENTIONAL NON-IMAGING FACTORS ALONE. TO VERIFY THESE HYPOTHESES, WE WILL RETROSPECTIVELY EVALUATE CT PANCREATIC IMAGES OBTAINED UP TO 3 YEARS PRIOR TO PDAC DIAGNOSIS THAT WERE DEEMED NON-CANCEROUS BY RADIOLOGISTS. A GROUP OF SUBJECTS WHO UNDERWENT SIMILAR IMAGING STUDIES FOR NON-GASTROINTESTINAL DISORDERS AND WERE AGE/GENDER MATCHED WITH PRE-DIAGNOSTIC IMAGING WILL SERVE AS HEALTHY CONTROLS. ACCURATELY STRATIFYING HIGH RISK INDIVIDUALS MAY ALLOW FOR EARLY DETECTION OF PDAC IN THE FUTURE. A MAJOR CHALLENGE OF THE PROJECT IS THE SCARCITY OF THE APPROPRIATE IMAGING DATA BECAUSE OF THE LOW PREVALENCE OF PDAC AND STRINGENT ENROLLMENT CRITERIA. EIGHT MAJOR MEDICAL CENTERS WILL PARTICIPATE IN COLLECTION OF 1,064 CASES. THE END POINT OF THIS PROJECT IS THE DEVELOPMENT, TRAINING, AND VALIDATION OF AN AI-BASED PDAC PREDICTION MODEL, WHICH WILL IDENTIFY INDIVIDUALS WHO ARE AT HIGH RISK FOR DEVELOPING PDAC WITHIN THE NEXT 3 YEARS.
assistance · Last action 2025-09-08
$4,827,743
Department of Health and Human Services
ROLE OF BLIMP-1 IN PREVENTING CHRONIC INTESTINAL MUCOSAL INFLAMMATION.
assistance · Last action 2025-05-30
$4,582,083
Department of Health and Human Services
INTRA-GRAFT C1 ESTERASE INHIBITOR THERAPY FOR DECEASED KIDNEY TRANSPLANTATION - KIDNEY TRANSPLANTATION IS THE OPTIMAL THERAPY FOR END STAGE KIDNEY DISEASE (ESKD) BUT CURRENT TRANSPLANT OUTCOMES ARE SUBOPTIMAL, PARTICULARLY FOR RECIPIENTS OF ORGANS OBTAINED FROM DECEASED DONORS (DD). ISCHEMIA REPERFUSION INJURY (IRI), WHICH OCCURS IN ESSENTIALLY ALL RECIPIENTS FOLLOWING DD KIDNEY TRANSPLANTATION, CONTRIBUTES TO POORER OUTCOMES IN DD TRANSPLANT RECIPIENTS. PRECLINICAL STUDIES IMPLICATE ACTIVATION OF THE COMPLEMENT SYSTEM THROUGH THE MANNAN BINDING LECTIN (MBL) PATHWAY AS ONE CRUCIAL DRIVER OF POST-TRANSPLANT IRI AND ITS DOWNSTREAM EFFECTS ON ALLOGRAFT FUNCTION. ADDITIONAL PRECLINICAL WORK SHOWED THAT BLOCKADE OF MBL COMPLEMENT ACTIVATION USING PERI-TRANSPLANT ADMINISTRATION OF C1 ESTERASE INHIBITOR (C1INH) CAN PROMOTE RECOVERY OF ALLOGRAFT FUNCTION FOLLOWING ISCHEMIA-REPERFUSION-(IR)-INDUCED ACUTE KIDNEY INJURY. OUR RESEARCH GROUP PERFORMED TWO SINGLE CENTER RANDOMIZED CONTROLLED PILOT TRIALS OF C1INH THERAPY TO LIMIT THE DOWNSTREAM CONSEQUENCES OF IRI IN HUMAN KIDNEY TRANSPLANT RECIPIENTS. THE RESULTS OF THESE PILOT TRIALS SUPPORT THE NOVEL HYPOTHESIS THAT COMPLEMENT SYSTEM INHIBITION WITH PRE-IMPLANTATION INJECTION OF C1 ESTERASE INHIBITOR (C1INH) INTO THE DONOR ORGAN RENAL ARTERY ALTERS THE REPARATIVE PROCESS INDUCED BY IR FOLLOWING DD KIDNEY TRANSPLANTATION AND IMPROVES ALLOGRAFT FUNCTION AT 1 YEAR. WE PROPOSE TO DETERMINE THE EFFECTS OF PRE- IMPLANTATION, INTRARENAL ARTERY INJECTION OF C1INH ON KIDNEY TRANSPLANT OUTCOMES THROUGH A RANDOMIZED CONTROLLED, DOUBLE BLIND, MULTICENTER TRIAL (AIM 1). WE WILL FOLLOW SUBJECTS FOR 12-MONTHS POST-TRANSPLANT TO ASSESS THE PRIMARY ENDPOINT OF EGFR. SECONDARY ENDPOINTS WILL BE BIOPSY PROVEN ACUTE REJECTION (BPAR) EFFICACY FAILURE (COMPOSITE OF BPAR, GRAFT LOSS, DEATH, AND LOSS TO FOLLOW UP), AND THE 12-MONTH ABBREVIATED IBOX SCORE. MULTIPLE EXPLORATORY ENDPOINTS INCLUDE DGF INCIDENCE/SEVERITY. ALL SUBJECTS WILL BE FOLLOWED FOR 3 YEARS TO ASSESS THE IMPACT OF THE INTERVENTION ON LONG TERM OUTCOMES. ASSOCIATED MECHANISTIC STUDIES (AIM 2) USING BIOPSY TISSUE AND PERIPHERAL BLOOD SAMPLES WILL PROVIDE INSIGHT INTO DETECTED ENDPOINT DIFFERENCES BETWEEN STUDY ARMS, IF OBSERVED, AND IF NO DIFFERENCES ARE DETECTED, WILL DETERMINE WHY THE INTERVENTION WAS INEFFECTIVE. APPROACHES WILL INCLUDE SPATIAL TRANSCRIPTOMICS, FUNCTIONAL IMMUNE ASSAYS, AND STUDIES OF GRAFT- DERIVED EXOSOMES, ALL PERFORMED USING STATE-OF-THE-ART TECHNIQUES. THE WORK WILL BE COMPLETED OVER 7 YEARS, WITH THE ABILITY TO DELIVER THE PRIMARY ENDPOINT CLINICAL RESULTS WITHIN 4-5 YEARS. THE ADDITIONAL TIME PERMITS EXTENDED FOLLOW-UP AND MECHANISTIC ANALYSES. THIS PROPOSED WORK ADDRESSES A KEY UNMET NEED IN KIDNEY TRANSPLANTATION, EMPLOYS A UNIQUE THERAPEUTIC STRATEGY, AND WILL BE PERFORMED BY AN EXPERIENCED TEAM. WE CONTEND THAT IF THE STUDY IS SUCCESSFUL IN IMPROVING POSTTRANSPLANT OUTCOMES, IT COULD TRANSFORM THE FIELD.
assistance · Last action 2025-08-25
$4,433,050
Department of Health and Human Services
THE ROLE OF MICRORNAS IN NORMAL AND DISEASED CORNEAL EPITHELIAL HOMEOSTASIS
assistance · Last action 2026-06-05
$4,294,987
Department of Health and Human Services
ASSESSMENT OF BIOMARKER GUIDED CNI SUBSTITUTION IN KIDNEY TRANSPLANTATION - CURRENT STANDARD OF CARE FOR KIDNEY TRANSPLANT (KTX) RECIPIENTS HAS ONLY MODESTLY IMPROVED LONG-TERM AGGREGATE GRAFT AND/OR PATIENT SURVIVAL, IDENTIFYING A CRUCIAL UNMET MEDICAL NEED. AS THE AT-RISK KTX POPULATION IS HETEROGENEOUS, THE CURRENTLY EMPLOYED AND RELATIVELY HOMOGENEOUS THERAPEUTIC APPROACH TO IMMUNOSUPPRESSION IN KTX IN THE US AND CANADA IS SUBOPTIMAL, AND RESULTS IN A SIGNIFICANT PROPORTION OF OVER- IMMUNOSUPPRESSED RECIPIENTS, MANY WITH TACROLIMUS-RELATED TOXICITIES. IN THIS U01 APPLICATION, CO-PIS HEEGER AND NICKERSON WILL BUILD UPON THEIR PAST, PRODUCTIVE COLLABORATIVE EFFORTS, THEIR ESTABLISHED MULTICENTER TRIAL CONSORTIUM AND INFRASTRUCTURE, AS WELL AS THEIR EXPERTISE IN BIOMARKERS AND MECHANISTIC STUDIES TO ADDRESS THIS UNMET NEED. THE OVERARCHING GOAL OF THE PROPOSED WORK IS TO DETERMINE THE UTILITY OF THE HLA-DR/DQ MOLECULAR MISMATCH (MMM) SCORE, AS A RISK STRATIFYING BIOMARKER IN KTX. WHILE RETROSPECTIVE STUDIES SHOWED STRONG CORRELATIONS BETWEEN THE HLA-DR/DQ MMM SCORE AND THE RISK OF DEVELOPING BIOPSY PROVEN ACUTE REJECTION (BPAR) AND/OR DONOR SPECIFIC ANTIBODIES (DSA), NO PROSPECTIVE STUDIES HAVE TESTED THE HLA MMM SCORE AS A RISK STRATIFYING BIOMARKER FOR IMMUNOLOGICAL KTX INJURY. NOR HAVE ANY STUDIES ATTEMPTED TO TEST WHETHER AND HOW THE HLA-DR/DQ MMM SCORE PERFORMS AS A PREDICTOR OF OUTCOME FOLLOWING A CHANGE IN TRANSPLANT IMMUNOSUPPRESSION. HEREIN, WE PROPOSE A MULTICENTER OBSERVATIONAL STUDY WITH A NESTED RANDOMIZED CONTROLLED (RCT) TRIAL TO ADDRESS THESE DEFICIENCIES. WE WILL PROSPECTIVELY TEST THE UTILITY OF THE HLA-DR/DQ MMM SCORE AS A PROGNOSTIC BIOMARKER OF PRIMARY ALLOIMMUNITY [T CELL MEDIATED REJECTION (TCMR), DSA, AND ANTIBODY MEDIATED REJECTION (ABMR)] IN KTX (AIM 1, OBSERVATIONAL STUDY OF 800 KTX). WE WILL ALSO TEST THE HYPOTHESIS THAT THE HLA-DR/DQ MMM SCORE IS A PREDICTIVE BIOMARKER THAT IDENTIFIES KTX RECIPIENTS WHO WILL TOLERATE SUBSTITUTING THE CALCINEURIN INHIBITOR WITH SELF-ADMINISTERED, SUBCUTANEOUS ABATACEPT (COSTIMULATORY BLOCKADE), WITHOUT AN UNACCEPTABLE INCREASED RISK OF BPAR, WHILE REDUCING THE MORBIDITY OF CNI OFF-TARGET EFFECTS (300 KTX, NESTED RCT WITH A NON-INFERIORITY ENDPOINT, AIM 2). ACCOMPANYING MECHANISTIC STUDIES (AIM 3) WILL PROVIDE NOVEL IMMUNOLOGICAL AND MOLECULAR INSIGHTS THAT WILL ALSO AID IN INTERPRETING GRAFT AND RECIPIENT OUTCOMES OF THE TRIAL. IF SUCCESSFUL, THE WORK WILL PROVIDE CRUCIAL INFORMATION CAPABLE OF POSITIVELY, AND DIRECTLY AFFECTING CLINICAL CARE. THE RESULTS FROM THE PROPOSED WORK ALSO HAVE THE POTENTIAL TO INFLUENCE POSITIVELY THE DESIGN OF FUTURE RCTS BY PROVIDING AN HLA-DR/DQ MMM SCORE-BASED STRATIFICATION OR ENRICHMENT STRATEGY FOR ENROLLING SUBJECTS INTO TRIALS MOST LIKELY TO BE INFORMATIVE FOR THE PROPOSED STUDY AGENT-- THEREBY INCREASING LIKELIHOOD OF TRIAL SUCCESS IN THE SHORTEST POSSIBLE TIME.
assistance · Last action 2022-06-27
$4,138,693
Department of Health and Human Services
TIME-RESTRICTED EATING AND CANCER: CLINICAL OUTCOMES, MECHANISMS, AND MODERATORS - ABSTRACT COMBINING FASTING WITH CHEMOTHERAPY CAN CAUSE COMPLETE TUMOR REGRESSION IN ANIMAL MODELS. ACUTE FASTING IS THOUGHT TO SENSITIZE TUMOR CELLS TO THE CYTOTOXIC EFFECTS OF CHEMOTHERAPY AND RADIATION, WHILE PROTECTING HEALTHY CELLS BY INCREASING STRESS RESISTANCE—A PHENOMENON KNOWN AS THE DIFFERENTIAL STRESS SENSITIZATION THEORY. HOWEVER, THE POTENTIAL RISKS OF EXTENDED CALORIC RESTRICTION HAMPER CLINICAL IMPLEMENTATION. TIME-RESTRICTED EATING (TRE) IS A PROMISING ALTERNATIVE, WHICH INVOLVES EATING WITHIN A PERIOD OF 10 HOURS OR LESS, FOLLOWED BY FASTING FOR AT LEAST 14 HOURS DAILY. BECAUSE OF ITS SIMPLICITY, TRE MAY BE MORE SUSTAINABLE. MOREOVER, OUR PILOT DATA SUGGEST THAT TRE HAS SEVERAL ANTI-CANCER EFFECTS: IT DECREASES IGF-1 LEVELS, REDUCES OXIDATIVE STRESS, UPREGULATES ANTIOXIDANT DEFENSES, AND ENHANCES AUTOPHAGY. WE PROPOSE TO CONDUCT THE FIRST CLINICAL TRIAL OF TRE IN CANCER PATIENTS UNDERGOING ACTIVE TREATMENT, AS WELL AS THE LARGEST RANDOMIZED CONTROLLED TRIAL OF ANY FORM OF INTERMITTENT FASTING IN CANCER PATIENTS. WE WILL FOCUS ON RECTAL CANCER BECAUSE IT IS ONE OF ONLY A COUPLE CANCERS WHERE TUMOR SIZE AND CHARACTERISTICS CAN BE MEASURED BEFORE AND AFTER TREATMENT. WE WILL ENROLL 300 NEWLY DIAGNOSED LOCALIZED RECTAL CANCER PATIENTS (STAGE II-III) AGED =18 (BMI = 18.5 KG/M2). ALL PARTICIPANTS WILL RECEIVE THE STANDARD OF CARE DURING ONCOLOGICAL TREATMENT AT CEDARS-SINAI MEDICAL CANCER (LOS ANGELES, CA) OR THE UNIVERSITY OF ALABAMA O’NEAL COMPREHENSIVE CANCER CENTER (BIRMINGHAM, AL) AND BE RANDOMIZED TO ONE OF TWO EATING SCHEDULES: (1) CONTROL SCHEDULE: 12-HOUR OR LONGER DAILY EATING PERIOD; (2) TRE: 8-HOUR DAILY EATING PERIOD (16 HOURS OF DAILY FASTING). PARTICIPANTS WILL BE COUNSELED TO MAINTAIN THEIR WEIGHT. ALL ENDPOINTS WILL BE MEASURED AT LEAST THREE TIMES: AT DIAGNOSIS PRIOR TO THE ONSET OF CHEMORADIATION (BASELINE), AFTER CHEMORADIATION TREATMENT, AND AT TUMOR RESECTION (POST-INTERVENTION). OUR PRIMARY AIM IS TO DETERMINE HOW TRE AFFECTS CLINICAL OUTCOMES, INCLUDING TREATMENT-RELATED ADVERSE EFFECTS (TOXICITY INDEX BASED ON CTCAE V.5), PATIENT-REPORTED OUTCOMES (PRO-CTCAE) AND QUALITY OF LIFE (EORTC QLQ-C30), AND CLINICAL (CCR) AND PATHOLOGICAL (PCR) COMPLETE RESPONSE RATES. AIM 2 TESTS THE DIFFERENTIAL STRESS SENSITIZATION THEORY—THE FIRST COMPLETE TEST OF THIS THEORY IN HUMANS. WE TEST WHETHER TRE ACTS THROUGH THE IGF-1 PATHWAY TO INCREASE STRESS RESISTANCE IN HEALTHY CELLS (DNA DAMAGE AND ANTIOXIDANT DEFENSES AS MEASURED BY GAMMA-H2AX AND TOTAL ANTIOXIDANT CAPACITY, RESPECTIVELY) AND ENHANCE TUMOR CELL DEATH (APOPTOSIS AND AUTOPHAGY AS MEASURED BY ACTIVATED CASPASE-3 AND LC3-I/LC3-II, RESPECTIVELY). AIM 3 COMPARES LONGITUDINAL CHANGES IN MOOD, SOCIAL FUNCTIONING, SLEEP, DIET, AND DAILY PHYSICAL ACTIVITY ACROSS INTERVENTION ARMS (CONTROL VS. TRE) AND EXPLORE HOW THESE CHANGES INTERACT WITH INTERVENTION ARMS TO PREDICT CLINICAL OUTCOMES. WE EXPECT THIS INNOVATIVE TRIAL WILL HELP IMPROVE CANCER TREATMENT OUTCOMES AND RESHAPE THE STANDARD OF CARE FOR CANCER PATIENTS.
assistance · Last action 2026-05-29
$4,123,295
Department of Health and Human Services
ROLE OF MACROPHAGES IN CONTROL OF OCULAR HSV
assistance · Last action 2026-06-01
$4,057,063
Department of Health and Human Services
RANDOMIZED-CONTROLLED TRIAL OF VIRTUAL REALITY FOR CHRONIC LOW BACK PAIN TO IMPROVE PATIENT-REPORTED OUTCOMES AND PHYSICAL ACTIVITY
assistance · Last action 2026-02-26
$4,055,184
Department of Health and Human Services
CONSORTIUM ON INTESTINAL REGENERATION AND FETAL REVERSION: FROM ATLAS TO THERAPY - ABSTRACT FETAL REVERSION IS A NOVEL REGENERATIVE PHENOMENON IN WHICH CELLS OF THE INTESTINAL EPITHELIUM RESPOND TO DAMAGE BY DOWNREGULATING THE NORMAL GENE EXPRESSION PROGRAM OBSERVED DURING HOMEOSTASIS AND BY ACQUIRING A FETAL- LIKE TRANSCRIPTIONAL STATE THAT PROMOTES CELL PROLIFERATION AND INTESTINAL REPAIR. FETAL REVERSION HAS BEEN OBSERVED IN DIFFERENT INTESTINAL INJURY MODELS IN THE MOUSE, INCLUDING DAMAGE FROM PARASITIC OR VIRAL INFECTION, RADIATION, AND CHEMICAL INSULTS. IT IS UNKNOWN IF FETAL REVERSION IS A UNIVERSAL PROPERTY OF INTESTINAL HEALING OR IF IT OCCURS ONLY DURING CERTAIN TYPES OF REPAIR. RECENT EVIDENCE INDICATES THAT THIS PHENOMENON MAY ALSO OCCUR IN THE HUMAN INTESTINE; HOWEVER, THIS HAS ALSO NOT BEEN INTERROGATED IN A SYSTEMATIC WAY. THIS PROJECT WILL CREATE A UNIQUE LARGE-SCALE RESEARCH RESOURCE – AN ATLAS OF INTESTINAL INJURY ACROSS MULTIPLE SPECIES (MOUSE, HUMAN) AND DAMAGE MODELS THAT CONTAINS COMPREHENSIVE SINGLE CELL MULTIOMIC DATASETS OF REGULATORY AND TRANSCRIPTIONAL DYNAMICS DURING INTESTINAL REPAIR AFTER INJURY. THE ATLAS WILL BE A TOOL FOR FUTURE HYPOTHESIS GENERATION FOR FUNCTIONAL STUDIES AND WILL BE AN IMPORTANT COMMUNITY-WIDE RESOURCE AVAILABLE TO THE ENTIRE SCIENTIFIC COMMUNITY. GENES AND PATHWAYS ESSENTIAL FOR FETAL REVERSION, AND FOR ANY OTHER COMMON INTESTINAL REGENERATION PROGRAMS, WILL BE IDENTIFIED USING ATLAS DATA. FUNCTIONAL STUDIES TO EXPLORE PATHWAYS AND GENES WILL BE CONDUCTED IN MOUSE MODELS THROUGH GAIN- AND LOSS-OF-FUNCTION EXPERIMENTS AND WILL BE INTERROGATED IN THE HUMAN CONTEXT USING INTESTINAL ORGANOIDS AS A MODEL SYSTEM. A HIGH-THROUGHPUT DRUG SCREENING ASSAY WILL BE USED TO IDENTIFY COMPOUNDS THAT INDUCE FETAL REVERSION, AND TOP COMPOUNDS IDENTIFIED WILL BE ASSESSED FOR THEIR ABILITY TO INDUCE THE FETAL REVERSION STATE THROUGH TRANSCRIPTOMIC AND EPIGENOMIC ASSAYS, AND TO ENHANCE ORGANOID-ENGRAFTMENT AND INJURY REPAIR IN VIVO THROUGH TRANSPLANTATION ASSAYS. THIS PROJECT WILL CREATE A MULTI-SPECIES INJURY-REPAIR ATLAS AND COMPREHENSIVELY CHARACTERIZE DIFFERENT MODES OF INTESTINAL REGENERATION, INCLUDING FETAL REVERSION, PROVIDING AN UNPRECEDENTED UNDERSTANDING OF INTESTINAL INJURY- REPAIR. ALL DATA, ANALYSES, METHODS, MODELS AND SCREENING PROTOCOLS WILL BE SHARED WITH THE RESEARCH COMMUNITY FOR EXPLORATION AND FURTHER ANALYSIS FOLLOWING ESTABLISHED SHARING MODELS. THE STUDIES PROPOSED HERE WILL IDENTIFY COMMON AND UNIQUE REGENERATIVE PROGRAMS THAT ARE ACTIVE IN DIFFERENT INJURY CONTEXTS, CREATING A PARADIGM SHIFT IN OUR UNDERSTANDING OF GUT REPAIR, AND LAYING THE FOUNDATION FOR NEW FIELDS OF RESEARCH AND THERAPEUTICS.
assistance · Last action 2025-07-16
$4,000,000
Department of Health and Human Services
IS OBESITY AN INFECTIOUS DISEASE?: GUT BACTERIAL AND FUNGAL TRANSLOCATION AS AN UNDERAPPRECIATED DRIVER OF VISCERAL ADIPOSE EXPANSION. - PROJECT SUMMARY/ABSTRACT CURRENTLY, OVER 70% OF THE U.S. ADULT POPULATION IS OVERWEIGHT OR OBESE, AND THIS NUMBER IS ONLY INCREASING. EVEN MORE ALARMING IS THAT 1 IN 6 CHILDREN IS NOW OVERWEIGHT OR OBESE, A NUMBER THAT HAS BEEN RISING EVEN MORE RAPIDLY THAN THE ADULT POPULATION. WHILE LIFESTYLE MODIFICATIONS AND GASTRIC BYPASS SURGERIES ARE PROVEN APPROACHES TO REDUCING ADIPOSITY AND METABOLIC DYSFUNCTION, THERE IS STILL NO SIGN THAT OBESITY AND ITS CO- MORBIDITIES ARE ABATING. SAFE, NEW STRATEGIES TO MITIGATE WEIGHT GAIN, IN COMBINATION WITH LIFESTYLE CHOICES, MAY PROVE MORE EFFECTIVE THAN ANY ONE STRATEGY ALONE. OUR LONG-TERM GOAL FOR THIS CATALYST PROJECT IS TO DEVELOP AN OBESITY-MITIGATING STRATEGY THAT LEVERAGES THE ACTIVITIES OF THE GUT MICROBIOME TO SELECTIVELY TARGET VISCERAL ADIPOSE DEPOTS. OUR RATIONALE FOR THIS IS BASED ON RECENT FINDINGS FROM MY LAB WHILE STUDYING CROHN’S DISEASE. WE REPORTED THAT CERTAIN LIPID-LOVING BACTERIA AND FUNGI IN THE GUT, CAN TRANSLOCATE FROM THE GUT TO MESENTERIC VISCERAL ADIPOSE TISSUE IN CROHN’S DISEASE PATIENTS. THE INTERACTION OF THESE MICROORGANISMS IN THE ADIPOSE TISSUE, PROMOTED TISSUE EXPANSION AND THE PHENOMENON KNOWN AS ‘CREEPING FAT’ (HA ET AL., CELL 2020). MANY FEATURES OF CROHN’S CREEPING FAT APPEAR SIMILAR TO OBESE VISCERAL ADIPOSE. THEREFORE, IF MICROBES MAY BE A POTENT DRIVER OF CREEPING FAT, PERHAPS THEY ARE A POTENT DRIVER OF VISCERAL ADIPOSITY IN OBESITY. OUR APPROACH TO THIS QUESTION WILL INVOLVE THE USE OF HUMAN GASTRIC BYPASS TISSUES TO FIRST CHARACTERIZE THE MICROBIAL PRESENCE IN THESE TISSUES, AND THEN TEST THESE ORGANISMS PROSPECTIVELY IN GNOTOBIOTIC MICE. WE WILL IN PARALLEL CREATE IPSC-DERIVED ORGANOIDS FROM OBESE PATIENTS TO TEST SPECIFIC HOST-MICROBE CELLULAR INTERACTIONS. THIS CONTRIBUTION IS INNOVATIVE BECAUSE IT POSES A RADICALLY NEW, FRINGE CONCEPT THAT GUT BACTERIA ARE DIRECTLY INTERACTING WITH ADIPOSE TISSUE TO INFLUENCE ITS BEHAVIOR. IF SO, WE MAY BE ABLE TO TARGET THESE SPECIFIC ORGANISMS IN THE GUT BEFORE THEY TRANSLOCATE, WHICH WE PROPOSE COULD BE ACHIEVED THROUGH PHAGE-MEDIATED KILLING RATHER THAN ANTIBIOTICS. IT IS HIGH-RISK BECAUSE THERE IS NO ESTABLISHED BODY OF LITERATURE TO SUPPORT THE NOTION THAT BACTERIA ARE DIRECTLY DRIVING THE BEHAVIOR OF ADIPOSE THROUGH CELL-CELL INTERACTIONS, BUT IF IT PROVES TO BE TRUE, WILL NECESSITATE A PARADIGM SHIFT IN HOW WE THINK ABOUT OBESITY. FINALLY, THE CONTRIBUTION IS SIGNIFICANT, BECAUSE IT MAY OPEN ENTIRELY NEW AVENUES FOR MAINTAINING METABOLIC HEALTH IN THE POPULATION, AND PARTICULARLY IN OUR MOST VULNERABLE, PEDIATRIC POPULATION.
assistance · Last action 2025-08-04
$3,971,090
Department of Health and Human Services
A NOVEL MECHANISM FOR NLRP3 INFLAMMASOME ACTIVATION IN HUMAN MACROPHAGES - INFECTIONS AND CELLULAR STRESS CAN TRIGGER CYTOPLASMIC PATTERN RECOGNITION RECEPTORS TO ASSEMBLE AN INFLAMMASOME COMPLEX, WHICH PROMOTES THE RELEASE OF THE INFLAMMATORY CYTOKINES IL-1SS, IL-18 AND THE INDUCTION OF PYROPTOTIC CELL DEATH. INFLAMMASOME RESPONSES ARE ALSO PERPETUATED AND PROPAGATED TO BYSTANDER CELLS. ULTIMATELY, THIS RESPONSE CONTRIBUTES TO PATHOGEN CLEARANCE AND WOUND HEALING. HOWEVER, EXCESSIVE INFLAMMASOME ACTIVATION CAN CONTRIBUTE TO- OR CAUSE DEBILITATING SYMPTOMS ASSOCIATED WITH INFLAMMATORY DISEASES. PARTICULARLY, THE NLRP3 INFLAMMASOME HAS BEEN DIRECTLY LINKED TO NUMEROUS DISEASES. IT HAS A UNIQUE POSITION BY NOT ONLY SENSING INFECTIONS, BUT ALSO CELLULAR STRESS AND TISSUE DAMAGE. EVEN THOUGH THE NLRP3 INFLAMMASOME IS OF UTMOST IMPORTANCE FOR BALANCING BETWEEN HOMEOSTASIS AND DISEASE, AND IS THEREFORE A PRIME TARGET FOR NOVEL TREATMENT STRATEGIES, THE UNDERLYING MOLECULAR MECHANISMS, PARTICULARLY IN HUMAN MACROPHAGES, ARE STILL POORLY UNDERSTOOD. THERE ARE NUMEROUS HUMAN INFLAMMASOME COMPONENTS THAT ARE ABSENT IN MICE AND THEIR FUNCTIONAL CONTRIBUTION TO HUMAN HEALTH AND DISEASE ARE EVEN LESS WELL UNDERSTOOD THAN THE MORE CONSERVED FACTORS. ELUCIDATING UNIQUE HUMAN RESPONSES IS THE MAIN FOCUS OF OUR LAB. INNATE IMMUNE RECEPTOR OLIGOMERIZATION INITIATES INFLAMMATORY HOST RESPONSES, INCLUDING INFLAMMASOME ACTIVATION. THE RESEARCH OUTLINED IN THIS PROPOSAL IS DESIGNED TO MECHANISTICALLY UNRAVEL A NOVEL NLRP3 INFLAMMASOME ACTIVATION CONCEPT IN HUMAN MACROPHAGES. WE DISCOVERED A NOVEL NLRP3 INFLAMMASOME COMPONENT IN HUMAN MACROPHAGES, WHICH INTERACTS WITH NLRP3, BUT IS ABSENT FROM MICE AND OUR PRELIMINARY STUDIES REVEALED THAT NLRP3 REQUIRES THIS CO-SENSOR FOR OLIGOMERIZATION AS WELL AS FOR RECRUITING THE INFLAMMASOME ADAPTOR, ASC. FURTHERMORE, NLRP3 AND ITS CO-SENSOR ARE NECESSARY FOR EFFICIENTLY NUCLEATING ASC POLYMERIZATION AND CASPASE-1 ACTIVATION. KNOCK OUT OF THE CO-SENSOR PHENOCOPIES NLRP3 KNOCK OUT IN HUMAN MACROPHAGES. SIGNIFICANTLY, IT IS ABSOLUTELY NECESSARY FOR CYTOKINE RELEASE DRIVEN BY NLRP3 MUTATIONS THAT CAUSE CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME (CAPS). WE PROPOSE TWO SPECIFIC AIMS THAT INVESTIGATE THE MECHANISM AND FUNCTION OF THE CO-SENSOR IN NLRP3 INFLAMMASOME ASSEMBLY AND ACTIVATION IN MACROPHAGES, AS WELL AS THE MOLECULAR EVENTS THAT ENABLE THIS CO-SENSOR TO PROMOTE NLRP3 INFLAMMASOME ACTIVATION. WE WILL UTILIZE CRISPR/CAS9 KNOCK OUT AND RESTORED EXPRESSION OF WILD TYPE AND MUTANT CO-SENSOR PROTEINS AND A HUMANIZED MOUSE EXPRESSING THE HUMAN CO-SENSOR FOR STUDYING ITS FUNCTION IN VIVO. WE EXPECT THAT OUR RESEARCH WILL UNCOVER NOVEL MOLECULAR MECHANISMS THAT NOT ONLY CHANGE OUR CURRENT UNDERSTANDING OF CONTROL MECHANISMS THAT PREVENT INAPPROPRIATE NLRP3 INFLAMMASOME ACTIVATION FOR MAINTAINING HOMEOSTASIS AND HUMAN HEALTH, BUT ALSO NLRP3-DRIVEN PATHOLOGIES IN INFLAMMATORY DISEASES. THE OUTCOMES OF OUR STUDY WILL MOVE THE FIELD FORWARD AND WILL BE HIGHLY SIGNIFICANT FOR UNDERSTANDING DISEASE PATHOLOGIES AND FOR THE DEVELOPMENT OF NOVEL THERAPIES THAT BENEFIT PATIENTS AND POSITIVELY AFFECT HUMAN HEALTH.
assistance · Last action 2026-02-05
$3,828,575
Department of Health and Human Services
THERAPEUTIC CONTROL OF HSK BY CD80
assistance · Last action 2025-09-16
$3,749,448
Department of Health and Human Services
WOMEN'S ISCHEMIA SYNDROME EVALUATION (WISE) - MECHANISMS OF CORONARY MICROVASCULAR DYSFUNCTION LEADING TO PRE-HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF)
assistance · Last action 2025-02-28
$3,748,443
Department of Health and Human Services
THE ROLE OF CHLAMYDIA PNEUMONIAE INFECTION IN ALZHEIMER'S DISEASE - LATE ONSET ALZHEIMER'S DISEASE (AD), A PROGRESSIVE IRREVERSIBLE SENILE DEMENTIA, IS THE SIXTH LEADING CAUSE OF DEATH IN THE ELDERLY, WITH AN ESTIMATED 5.7 MILLION AMERICANS AFFLICTED BY THIS DEBILITATING DISORDER. THESE NUMBERS ARE EXPECTED TO DOUBLE IN THE NEXT 20 YEARS, PRESENTING A SIGNIFICANT EMOTIONAL AND ECONOMIC BURDEN. WHILE AD RESEARCH CONTINUES TO BE A PRIORITY, LITTLE HEADWAY HAS BEEN MADE IN SLOWING DISEASE PROGRESSION, LET ALONE CURING IT. EARLY HYPOTHESES REGARDING THE CAUSE OF AD INCLUDED INFECTIOUS PARADIGMS, BUT THESE IDEAS WERE LARGELY DISCARDED AS THE UNDERSTANDING OF THE PATHOGENIC ROLE OF AMYLOID SS (ASS) GREW AND THE GENETIC UNDERPINNINGS OF EARLY ONSET AD WERE IDENTIFIED. HOWEVER, NEW DATA HAS LED RESEARCHERS TO ONCE AGAIN SUGGEST THAT INFECTIONS MAY PLAY A DEVELOPMENTAL AND/OR ACCELERATING ROLE IN AD PROGRESSION. AMONG INFECTIOUS ORGANISMS, CHLAMYDIA PNEUMONIAE (CP) HAS BEEN IDENTIFIED AS THE LEADING CANDIDATE FOR A PATHOGENIC ROLE IN AD. CP, A COMMON CAUSE OF COMMUNITY-ACQUIRED PNEUMONIA, HAS BEEN LINKED TO MANY CHRONIC INFLAMMATORY DISEASES, INCLUDING ATHEROSCLEROSIS, ASTHMA, LUNG CANCER, AND AD. IN ADDITION TO AN ASSOCIATION BETWEEN ANTI-CP ANTIBODY TITER AND AD, SEVERAL STUDIES HAVE IDENTIFIED CP IN THE BRAINS OF AD PATIENTS. HOWEVER, THE MECHANISMS BY WHICH CP INFECTION MAY ALTER AD PATHOGENESIS ARE UNKNOWN, AND NO DEFINITIVE MOUSE STUDIES HAVE BEEN PERFORMED. INFLAMMATORY CYTOKINES LIKE NLRP3/IL-1SS AND IL17, BOTH INVOLVED IN CP INFECTION INDUCED PATHOLOGY, MAY BE THE KEY DRIVERS FOR INFECTION –MEDIATED ACCELERATION OF AD, AND WILL BE TARGETED IN THIS APPLICATION. IN A PRELIMINARY STUDY WE FOUND CP ANTIGENS COLOCALIZING WITH ACTIVATED MICROGLIA IN THE BRAINS OF CP INFECTED APPSWE/PS1E9 MICE, CLEARLY PLACING CP IN THE RIGHT LOCATION TO INFLUENCE AD PROGRESSION. WE WERE ALSO ABLE TO IDENTIFY ASC SPECKS (ACTIVE INFLAMMASOME) IN THE BRAINS OF THESE MICE. OUR EXPERTISE IN CP INFECTION AND IMMUNE RESPONSES, IN COMBINATION WITH OUR CO-PI'S EXPERTISE IN AD, PUTS US IN A UNIQUELY STRONG POSITION TO INVESTIGATE THE RELATIONSHIP BETWEEN CP INFECTION AND AD, AND THE POTENTIAL OF ANTIBIOTIC THERAPY IN CP-ACCELERATED AD. BASED ON THESE DATA, WE HYPOTHESIZE THAT CP INFECTION PLAYS A ROLE IN PROGRESSION AND/OR DEVELOPMENT OF ALZHEIMER'S DISEASE, WHICH IS PREVENTABLE BY EARLY ANTIBIOTIC TREATMENT, AND THAT CP EFFECTS ARE AT LEAST PARTIALLY MEDIATED THROUGH ACTIVATION OF THE NLRP3 INFLAMMASOME AND IL-17A. IN ORDER TO TEST THESE HYPOTHESES, WE WILL INVESTIGATE THE FOLLOWING AIMS: 1) DETERMINE THE EFFECT OF CP INFECTION ON DISEASE PROGRESSION IN APPSWE/PS1E9 (ADTG) MICE AND 2) DETERMINE THE ROLE OF THE NLRP3 INFLAMMASOME IN CP INFECTION- MODULATED AD PATHOLOGY IN ADTG MICE AND IN PATIENTS WITH AD OR MILD COGNITIVE IMPAIRMENT (MCI) AND 3) DETERMINE THE ROLE OF IL-17A IN CP INFECTION-MODULATED AD-LIKE PATHOLOGY IN ADTG MICE. THE COMPLETION OF OUR PROPOSAL WILL LAY THE GROUNDWORK FOR UNDERSTANDING WHAT POSSIBLE ROLE CP INFECTION PLAYS IN AD. FURTHERMORE, THESE DATA WILL BE USED AS THE BASIS FOR FUTURE RESEARCH UNDERSTANDING THE MECHANISMS INVOLVED CP INFECTION ROLE IN AD WITH THE ULTIMATE GOAL LEADING TO NEW THERAPEUTIC APPROACHES FOR THIS DEVASTATING DISEASE.
assistance · Last action 2026-05-25
$3,728,669
Department of Health and Human Services
ADVANCING ANALYSIS AND INTERPRETATION OFADVERSE EVENTS AND PROS IN CANCER CLINICAL TRIALS
assistance · Last action 2026-01-28
$3,725,399
Department of Health and Human Services
EVALUATING ENVIRONMENTAL CONTROL (AVOID) AND INHIBITORY CONTROL (RESIST) STRATEGIES TO IMPROVE WEIGHT MANAGEMENT OUTCOMES - ABSTRACT EVIDENCE-BASED WEIGHT MANAGEMENT PROGRAMS ARE EFFECTIVE WHEN INDIVIDUALS ARE ABLE TO CONSISTENTLY ADHERE TO RECOMMENDATIONS. HOWEVER, A LARGE PROPORTION OF TREATMENT-SEEKING INDIVIDUALS DO NOT EXPERIENCE CLINICALLY SIGNIFICANT WEIGHT LOSS. INNOVATIVE STRATEGIES ARE NEEDED TO OPTIMIZE BEHAVIOR CHANGE IN WEIGHT MANAGEMENT INTERVENTIONS. THE PROPOSED RANDOMIZED CONTROLLED TRIAL TESTS TWO SELF-REGULATORY APPROACHES TO IMPROVE INTENTIONAL WEIGHT LOSS AND DIET QUALITY IN INDIVIDUALS WITH OVERWEIGHT OR OBESITY: (1) AN ENVIRONMENTAL CONTROL STRATEGY (AVOID) AND (2) AN IMPULSE CONTROL TRAINING STRATEGY (RESIST). SPECIFICALLY, 500 WOMEN AND MEN (BMI BETWEEN 25-39.9 KG/M2) WILL BE RECRUITED FROM THE CEDARS-SINAI MEDICAL CENTER NETWORK OF HOSPITALS AND CLINICS. ALL PARTICIPANTS WILL BE ENROLLED IN A 12-MONTH WEIGHT-MANAGEMENT PROGRAM (WW, FORMERLY WEIGHT WATCHERS©) FOCUSING ON DIET, PHYSICAL ACTIVITY AND MINDSET SKILLS, AND RANDOMIZED TO ONE OF FOUR STUDY ARMS: (1) WW ONLY, (2) WW + MODIFICATION OF HOME FOOD ENVIRONMENT AND ONLINE GROCERY DELIVERY (AVOID), (3) WW + GAMIFIED INHIBITORY CONTROL TRAINING (RESIST), (4) WW + AVOID + RESIST. BASELINE, 6- AND 12-MONTH ASSESSMENTS WILL BE COMPLETED BY EXPERIENCED, ENGLISH AND SPANISH SPEAKING STUDY STAFF. AIM 1 (OUTCOMES). (A) TESTS HOW AVOID AND RESIST AFFECT WEIGHT LOSS AND WAIST CIRCUMFERENCE (PRIMARY) AND DIET QUALITY (SECONDARY). H1A: AVOID AND/OR RESIST (ARMS 2, 3, 4) WILL RESULT IN GREATER WEIGHT LOSS AT 6-MONTH AND 12-MONTH TIMEPOINTS COMPARED TO WW ALONE. (B) TESTS POTENTIAL RIPPLE EFFECTS OF AVOID AND RESIST ON AVAILABLE HOUSEHOLD MEMBERS' DIET QUALITY (PRIMARY) AND WEIGHT (SECONDARY). H1B: WE PREDICT THAT AVOID (ARMS 2 AND 4) WILL PRODUCE GREATER DIETARY CHANGES IN HOUSEHOLD MEMBERS THAN WW ALONE AND RESIST (ARMS 1 AND 3). AIM 2 (MECHANISMS). TESTS THE MECHANISTIC PATHWAYS OF AVOID AND RESIST BY (A) COMPARING LONGITUDINAL CHANGES IN INHIBITORY CONTROL AND HOME FOOD ENVIRONMENT ACROSS STUDY ARMS; AND (B) WHETHER INHIBITORY CONTROL AND THE HOME FOOD ENVIRONMENT MEDIATE THE RELATIONSHIPS BETWEEN STUDY ARMS AND ANTHROPOMETRIC AND DIETARY OUTCOMES. H2: AVOID WILL PRODUCE CHANGES IN THE HOME FOOD ENVIRONMENT AND RESIST WILL OPERATE ON INHIBITORY CONTROL. AIM 3 (MODERATORS). EXAMINES HOW (A) INDIVIDUAL CHARACTERISTICS (AGE, SEX, ETHNICITY, SOCIOECONOMIC STATUS, HOUSEHOLD COMPOSITION, PHYSICAL ACTIVITY, BASELINE BMI AND EXECUTIVE FUNCTIONING), AND (B) PROCESS DATA (FREQUENCY OF GROCERY DELIVERY, DINING OUT AND TAKE OUT, IMPULSE CONTROL TRAINING AND WW APP USE) MODERATE THE RELATIONSHIP BETWEEN STUDY ARMS AND ANTHROPOMETRIC AND DIETARY OUTCOMES. THESE CONSIDERATIONS ARE IMPORTANT TO HELP EXPLAIN HETEROGENEITY IN INTERVENTION OUTCOMES AND TO UNDERSTAND WHO BENEFITS FROM AVOID AND/OR RESIST.
assistance · Last action 2026-01-30
$3,507,224
Department of Health and Human Services
AI METHODS FOR LARGE SCALE EPIDEMIOLOGICAL STUDIES USING PATIENT REPORTS OF MEDICATION ADHERENCE AND TOLERABILITY - PROJECT SUMMARY ADHERENCE TO PRESCRIBED MEDICATIONS IS A CRITICAL ASPECT OF EFFECTIVE MEDICAL TREATMENT, ESPECIALLY FOR CHRONIC CON- DITIONS; HOWEVER, THE WORLD HEALTH ORGANIZATION (WHO) ESTIMATES THAT MORE THAN 50% OF PATIENTS WITH CHRONIC CONDITIONS IN THE UNITED STATES DO NOT TAKE THEIR MEDICATIONS AS PRESCRIBED. MEDICATION NON-ADHERENCE IS ASSOCI- ATED WITH WORSENING HEALTH CONDITIONS AND INCREASED COMORBIDITIES, AND IS ESTIMATED TO ANNUALLY ACCOUNT FOR 25% OF HOSPITALIZATIONS, MORE THAN 100,000 PREVENTABLE DEATHS, AND UP TO $500 BILLION IN HEALTHCARE COSTS IN THE UNITED STATES. THE WHO AFFIRMS THAT “INCREASING THE EFFECTIVENESS OF ADHERENCE INTERVENTIONS MAY HAVE A FAR GREATER IMPACT ON THE HEALTH OF THE POPULATION THAN ANY IMPROVEMENT IN SPECIFIC MEDICAL TREATMENTS.” THE CHALLENGE OF INCREASING THE EFFECTIVENESS OF ADHERENCE INTERVENTIONS HAS LIKELY BEEN DUE IN PART TO THE FACT THAT THE MAJORITY OF MEDICATION NON-ADHERENCE IS INTENTIONAL (IN CONTRAST TO UNINTENTIONAL, SUCH AS FORGETFULNESS) AND SOURCES OF DATA FOR UNDERSTANDING THE FACTORS THAT INFLUENCE INTENTIONAL NON-ADHERENCE REMAIN LIMITED. AS ENCOURAGED BY THE UNITED STATES FOOD AND DRUG ADMINISTRATION AND CENTERS FOR DISEASE CONTROL AND PREVENTION, OUR PRIOR WORK—FUNDED FOR THE PAST 10 YEARS BY THE NATIONAL LIBRARY OF MEDICINE (R01LM011176)—HAS DEMONSTRATED THAT PATIENT REPORTS IN REAL-WORLD, NON-TRADITIONAL SOURCES OF DATA CAN BE USED AS A NOVEL, COMPLEMENTARY APPROACH TO POST-MARKETING PHARMACOVIGILANCE. BECAUSE ONLINE PATIENT REPORTS ARE NOT BIASED BY SURVEY QUESTIONS OR INTERVIEWERS, ARE AVAIL- ABLE ON A LARGE SCALE, AND MAY INCLUDE PARTICIPANTS WHO ARE UNDER-REPRESENTED IN TRADITIONAL SOURCES OF DATA, IN A PRELIMINARY QUALITATIVE CONTENT ANALYSIS, WE WERE ABLE TO GAIN NOVEL INSIGHTS ABOUT MEDICATION NON-ADHERENCE THAT WERE NOT WELL-REPRESENTED IN OTHER STUDIES, SUCH AS PATIENTS REPORTING DECHALLENGE (I.E., AN ADVERSE EFFECT STOPPING WHEN THE MEDICATION WAS STOPPED) AND RECHALLENGE (I.E., THE ADVERSE EFFECT RESUMING WHEN THE MEDICATION WAS STARTED AGAIN). VALIDATING OUR APPROACH THROUGH FIVE DISEASE-SPECIFIC CASE STUDIES IN COLLABORATION WITH DOMAIN EXPERTS IN CARDIOVASCULAR DISEASES, GASTROINTESTINAL DISEASES, CANCER, HIV, AND DIABETES (AIM 3), WE PROPOSE TO DEVELOP NOVEL NATURAL LANGUAGE PROCESSING AND ARTIFICIAL INTELLIGENCE METHODS (AN INTELLIGENT AGENT WITH A SPECIAL- IZED LARGE LANGUAGE MODEL AT ITS CORE) TO CAPTURE MEDICATION USE NARRATIVES FROM ONLINE PATIENT REPORTS (AIM 1) AND TO ELUCIDATE ADDITIONAL FACTORS CONTRIBUTING TO MEDICATION NON-ADHERENCE FROM SPONTANEOUS REPORTING SYSTEMS (SRS, E.G., FAERS), SUCH AS DRUG INDICATIONS, THE MAGNITUDE OF ADVERSE EVENTS, AND DRUG-DRUG INTERACTIONS (AIM 2). WE INCORPORATE FINDINGS FROM OTHER SOURCES INTO OUR CASE STUDIES THROUGH SYSTEMATIC REVIEWS (AIM 3), SYNTHE- SIZING AND COMPARING PUBLISHED STUDIES TO WHAT WE LEARN FROM PATIENT REPORTS POSTED ONLINE AND IN SRS. THIS IS THE MOST COMPREHENSIVE STUDY OF ITS KIND EVER ATTEMPTED, BRINGING THE VOICE OF THE PATIENTS DIRECTLY TO RESEARCHERS IN A REPRODUCIBLE, COST-EFFECTIVE MANNER. THIS CAN INFORM ADHERENCE INTERVENTIONS AND REDUCE THE MORBIDITY, MORTALITY, AND FINANCIAL BURDEN ASSOCIATED WITH INTENTIONAL NON-ADHERENCE, ALIGNING WITH THE NLM’S GOAL OF CREATING A FUTURE IN WHICH DATA AND INFORMATION TRANSFORM AND ACCELERATE BIOMEDICAL DISCOVERY AND IMPROVE HEALTH AND HEALTHCARE.
assistance · Last action 2025-09-15
$3,484,662
Department of Health and Human Services
METHIONINE ADENOSYLTRANSFERASE ALPHA1 IN ALCOHOLIC LIVER DISEASE
assistance · Last action 2026-04-01
$3,421,824
Department of Health and Human Services
OCULAR HSV: MECHANISM OF VIRUS REACTIVATION
assistance · Last action 2026-02-02
$3,358,083
Department of Health and Human Services
MULTIPARAMETRIC PET/MRI ASSESSMENT OF MAST CELL STABILIZATION EFFECTS ON INFLAMMAGING AND GLUCOSE UTILIZATION IN INFARCTED MYOCARDIUM - PROJECT SUMMARY INSULIN RESISTANCE (IR) IN AGING HEARTS OF NONDIABETICS IS KNOWN TO BE PROMOTED BY FAT ACCUMULATION WITHIN SENESCENT MYOCARDIUM IN THE ABSENCE OF OBESITY OR PHYSICAL INACTIVITY. IMPORTANTLY, THESE CHANGES MAKE THE AGED MYOCARDIUM MORE SUSCEPTIBLE TO HEART FAILURE AND SUDDEN DEATH. SIMILARLY, AGING OF INFARCTED MYOCARDIUM IN NONDIABETIC SUBJECTS IS COMMONLY ACCOMPANIED BY FAT ACCUMULATION IN MYOCARDIAL SCAR TISSUE (LIPOMATOUS METAPLASIA, LM). HOWEVER, WHETHER LM INFLUENCES MYOCARDIAL IR, REMAINS UNKNOWN. RECENT STUDIES USING A NONDIABETIC RAT MODEL HAVE DEMONSTRATED DIRECT EVIDENCE OF SELECTIVE MYOCARDIAL IR IN CHRONIC MIS WITH HEART FAILURE. HOWEVER, IT REMAINS UNKNOWN WHETHER THESE MIS ALSO HAD LM. CARDIAC INFLAMMAGING POST-MI IS A STATE OF CHRONIC LOW-GRADE STERILE INFLAMMATION THAT PLAYS A KEY ROLE IN THE ONSET AND PROGRESSION OF HEART FAILURE. IT IS A MAST CELL (MC)- AND MACROPHAGE (MF)-DRIVEN PROCESS CHARACTERIZED BY A COMPLEX BALANCE BETWEEN PRO- AND ANTI-INFLAMMATORY RESPONSES. EQUALLY IMPORTANT, THE PREPONDERANCE OF MC AND PROINFLAMMATORY M1 MF WITHIN ADIPOSE TISSUE (AT) IS NOW RECOGNIZED AS A HALLMARK OF OBESITY- ASSOCIATED LOW-GRADE INFLAMMAGING WHICH LEADS TO REDUCED EXPRESSION OF ADIPOCYTE GLUCOSE TRANSPORTER (GLUT4) AND SYSTEMIC IR. SYSTEMIC IR HAS BEEN COMMONLY OBSERVED IN NONDIABETIC PATIENTS WITH ISCHEMIC POST-MI CARDIOMYOPATHY. HOWEVER, WHETHER THESE SUBJECTS ALSO EXHIBIT MYOCARDIAL IR AND/OR LM, IS UNKNOWN. METABOLIC STATE AND THE PHENOTYPE OF MC AND MF THROUGHOUT THE INFLAMMATORY PROCESS ARE TIGHTLY LINKED. WHILE ACTIVATED MC AND M1 MF ARE HIGHLY DEPENDENT ON GLUCOSE AS AN ENERGY SUBSTRATE, ANTI-INFLAMMATORY M2 MF ARE PREFERENTIALLY FUELED BY FATTY ACID SS-OXIDATION. LIPID-OVERLOADING AND INSULIN (HYPER) STIMULATION HAVE EACH BEEN DEMONSTRATED TO PROMOTE MC ACTIVATION, M1 POLARIZATION, AND MF FOAM CELL FORMATION, THUS INITIATING THE PROCESS OF ATHEROGENESIS. MOREOVER, THE PRO-ATHEROGENIC EFFECTS OF MCS WERE SHOWN TO BE SUCCESSFULLY ABOLISHED VIA MC MEMBRANE STABILIZATION. NOTABLY, MC AND LIPID-LADEN M1 MF HAVE EACH BEEN DEMONSTRATED IN INFARCTED TERRITORY BEYOND SUBACUTE PHASE OF MI. HOWEVER, THEIR LONG-TERM FATE, THE INTERACTION BETWEEN THE TWO, AND THEIR RESPECTIVE ROLES IN LM AND/OR IR REMAIN UNKNOWN. WHILE 18F-FLUORODEOXYGLUCOSE (18FDG) PET HAS EMERGED AS A NON-INVASIVE IMAGING OF CHOICE TO ASSESS MYOCARDIAL IMMUNOMETABOLIC STATE AND TO DIAGNOSE MYOCARDIUM-SPECIFIC IR, QUANTITATIVE CARDIAC MR (QCMR) IS NOW WIDELY ACCEPTED AS THE GOLD STANDARD FOR THE QUANTITATIVE ESTIMATION OF INFARCT SIZE AND TISSUE COMPOSITION. HEREIN, WE PROPOSE TO USE A COMBINED 18FDG-PET/QCMR IMAGING TO EVALUATE THE EFFECTS OF MC STABILIZATION ON METABOLIC PHENOTYPE AND REMODELING OF MI, IN A PORCINE MODEL.
assistance · Last action 2026-05-05
$3,306,276
Department of Health and Human Services
ASSESSMENT OF MAST CELL DEGRANULATION IN INFARCTED MYOCARDIUM USING QUANTITATIVE MULTIPARAMETRIC MRI - PROJECT SUMMARY THE OVERALL OBJECTIVE OF THE PROPOSED PROJECT IS TO EVALUATE THE EFFECTIVENESS OF A NOVEL PHARMACOLOGICAL TREATMENT OF MYOCARDIAL INFARCTION (MI) USING QUANTITATIVE MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING (QMRI). MI IS A MAJOR CAUSE OF DEATH AND DISABILITY WORLDWIDE. URGENT REPERFUSION OF THE OCCLUDED ARTERY TO RESTORE MYOCARDIAL BLOOD FLOW IS CENTRAL TO THE CLINICAL MANAGEMENT OF ACUTE THROMBOTIC MI (AMI). HOWEVER, RECANALIZATION OF THE CULPRIT ARTERY MAY ALSO RESULT IN UNINTENDED INJURY BY CAUSING MICROVASCULAR OBSTRUCTION (MVO), INTRAMYOCARDIAL HEMORRHAGE (IMH), AND EDEMA DURING THE ACUTE PHASE. IN THE SETTING OF CHRONIC MI, IRON DEPOSITION AND FAT ACCUMULATION (LIPOMATOUS METAPLASIA, LM) ARE FREQUENTLY OBSERVED IN INFARCTED MYOCARDIUM. ALL THESE BIOMARKERS ARE STRONG PREDICTORS OF MAJOR ADVERSE CARDIOVASCULAR EVENTS SUCH AS HEART FAILURE. TO DATE, HOWEVER, THERE HAVE BEEN NO EFFECTIVE THERAPEUTIC STRATEGIES FOR ATTENUATING EITHER MVO, IMH, CHRONIC IRON DEPOSITION, OR LM POST-REPERFUSION. MAST CELLS (MC) ARE DERIVED FROM BLOOD-BORNE, MULTIPOTENT HEMATOPOIETIC PROGENITOR CELLS THAT, ONCE LOCATED IN TISSUE, DIFFERENTIATE TO A FINAL PHENOTYPE UNDER THE INFLUENCE OF THE LOCAL MICROENVIRONMENT. IN GENERAL, MC EXERT THEIR PHYSIOLOGICAL AND PATHOLOGICAL FUNCTIONS BY RELEASING CYTOPLASMIC GRANULES (DEGRANULATION) CONTAINING A VARIETY OF BIOLOGICALLY ACTIVE MEDIATORS. RECENT EXPERIMENTAL STUDIES HAVE SHOWN THAT HEMATOMA GROWTH, EDEMA EXPANSION AND OVERALL NEUROLOGICAL DAMAGE AFTER CEREBRAL ISCHEMIA- REPERFUSION CAN BE REDUCED BY EARLY TREATMENT WITH MC STABILIZERS, WHICH ARE KNOWN TO SUPPRESS MC DEGRANULATION. EQUALLY IMPORTANT, ATHEROSCLEROSIS RESEARCH OVER THE LAST TWO DECADES HAS PROVIDED STRONG EVIDENCE FOR MC INVOLVEMENT IN FOAM CELL FORMATION AND PLAQUE DEVELOPMENT. BASED ON THESE STUDIES, WE HYPOTHESIZED THAT MC STABILIZATION VIA THE ADMINISTRATION OF OVER-THE-COUNTER ANTI-ALLERGY MEDICATION LORATADINE REDUCES MYOCARDIAL EDEMA, IMH VOLUME AND IMPROVES MYOCARDIAL MICROCIRCULATION IN THE ACUTE MI SETTING; AND ATTENUATES LM OF INFARCTED MYOCARDIUM IN THE CHRONIC PHASE. QUANTITATIVE CARDIOVASCULAR MR (QCMR) IMAGING HAS BEEN WIDELY USED TO CHARACTERIZE MYOCARDIAL ISCHEMIA, HEMORRHAGE, EDEMA, INFLAMMATION, IRON DEPOSITION, FAT ACCUMULATION AND OTHER PATHOLOGICAL CONDITIONS. IN THIS PROPOSAL, WE AIM TO VALIDATE THE EFFECTIVENESS OF MC STABILIZER LORATADINE ON STRUCTURAL AND FUNCTIONAL CARDIAC REMODELING POST-PHARMACOTHERAPY IN A PORCINE MODEL OF MI BY TEMPORALLY FOLLOWING IMAGING BIOMARKERS OF ACUTE AND CHRONIC MI USING WELL-ESTABLISHED QCMR TECHNIQUES. SUCCESSFUL COMPLETION OF THE PROJECT WILL PROVIDE INITIAL VALIDATION THAT EARLY LORATADINE INTERVENTION HAS THE POTENTIAL TO BE A NOVEL THERAPEUTIC STRATEGY FOR PREVENTION OF HEART FAILURE POST-MI AS EVALUATED BY OUR QUANTITATIVE MULTIPARAMETRIC MRI APPROACH.
assistance · Last action 2026-04-23
$3,298,936
Department of Health and Human Services
IL-27R SIGNALING AS A NEGATIVE REGULATOR OF INNATE AND ADAPTIVE ANTI-CANCER IMMUNITY IN HEPATOCELLULAR CARCINOMA - PROJECT SUMMARY LIVER CANCER RANKS FIFTH IN FREQUENCY AND THIRD IN MORTALITY, WITH ESTIMATED NUMBERS OF OVER 700,000 NEW CASES EVERY YEAR WORLDWIDE. HEPATOCELLULAR CARCINOMA (HCC) IS THE MOST COMMON FORM OF LIVER CANCER THAT ORIGINATES FROM VIRAL INFECTION (E.G., HEPATITIS B, C) OR INJURY-DRIVEN CHRONIC INFLAMMATION (E.G., CIRRHOSIS FROM EXCESSIVE ALCOHOL CONSUMPTION OR OBESITY-INDUCED STEATOHEPATITIS) IN THE LIVER. ALTHOUGH HBV AND HCV INCIDENCE ARE ON THE DECLINE, THE OBESITY EPIDEMIC HAS RESULTED IN AN INCREASE IN THE NUMBER OF NEW CASES OF HCC IN DEVELOPED COUNTRIES INCLUDING THE US. THUS, IDENTIFYING TARGETABLE MEDIATORS OF HCC REPRESENTS AN IMPORTANT UNMET MEDICAL NEED. INTERLEUKIN (IL)-27 IS A CYTOKINE THAT PLAYS IMMUNOMODULATORY ROLES IN INFECTION AND AUTOIMMUNITY. IL27R SIGNALING REDUCES INFLAMMATION IN INFECTIOUS AND INFLAMMATORY MODELS OSTENSIBLY BY SUPPRESSING A PRO- INFLAMMATORY IMMUNE RESPONSE. THESE FINDINGS LED US TO SPECULATE THAT IL27 MIGHT FUNCTION SIMILARLY TO LIMIT LIVER INFLAMMATION AND HALT HCC DEVELOPMENT. SURPRISINGLY, HOWEVER, WE HAVE DISCOVERED THAT ELIMINATING IL27R SIGNALING SUPPRESSES TUMOR DEVELOPMENT IN TWO IN VIVO MOUSE MODELS OF HCC WHICH WAS ACCOMPANIED BY THE INCREASED ACCUMULATION AND ACTIVATION OF INNATE AND ADAPTIVE CYTOTOXIC IMMUNE CELLS, SUGGESTING A NEW, PRO- TUMORIGENIC ROLE FOR THIS OTHERWISE ANTI-INFLAMMATORY CYTOKINE. HERE WE PROPOSE TO INVESTIGATE CELLULAR AND MOLECULAR MECHANISMS OF HOW IL27R SIGNALING SUPPRESSES ANTI-CANCER CYTOTOXIC IMMUNE RESPONSE USING HIGHLY RELEVANT TO HUMAN HCC MUP-UPA MOUSE MODEL COMBINED WITH CELL TYPE SPECIFIC ABLATION OF IL27R AND INTEGRATED ARRAY OF CUTTING-EDGE TRANSCRIPTOMICS, HISTOLOGICAL, IMMUNOLOGICAL, AND MOLECULAR BIOLOGY ANALYSES. FINALLY, WE WILL TEST THE EFFICACY AND IDENTIFY CELLULAR AND MOLECULAR MECHANISMS OF IL27 SIGNALING BLOCKADE EITHER ALONE OR IN COMBINATION WITH OTHER IMMUNOTHERAPIES, AS A NEW THERAPEUTIC AVENUE FOR HCC. OVERALL, THE PROPOSED RESEARCH WILL UNCOVER THE ROLE OF IL27R SIGNALING IN HCC DEVELOPMENT AND DETERMINE THE BENEFICIAL MECHANISMS OF ITS BLOCKADE. THIS WORK HAS STRONG TRANSLATIONAL POTENTIAL WITH GAME- CHANGING RAMIFICATIONS FOR HCC.
assistance · Last action 2026-05-04
$3,273,154
Department of Health and Human Services
MYOCARDIAL STEATOSIS IN WOMEN WITH CORONARY MICROVASCULAR DYSFUNCTION: DEFINING THE PATHWAY TO HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) - PROJECT SUMMARY HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) CONTINUES TO POSE A MAJOR BURDEN TO THE HEALTHCARE SYSTEM, WOMEN ARE TWICE AS LIKELY AS MEN TO DEVELOP HFPEF, AND NO TARGETED THERAPIES FOR HFPEF EXIST. CORONARY MICROVASCULAR DYSFUNCTION (CMD), DEFINED AS IMPAIRED FUNCTION OF THE SMALL MICROVESSELS WITHIN THE HEART, IS A WIDELY PREVALENT YET POORLY UNDERSTOOD CONDITION THAT ALSO PREDOMINANTLY AFFECTS WOMEN. HFPEF IS THE MOST FREQUENTLY EXPERIENCED MORBID OUTCOME IN WOMEN WITH CMD, WHO ARE OFTEN YOUNGER THAN THOSE WITH OTHER HFPEF PHENOTYPES. WHILE WE AND OTHERS HAVE SHOWN THAT HFPEF IS PRESENT IN UP TO A THIRD OF WOMEN WITH CMD, THE PATHOBIOLOGY OF CMD-RELATED HFPEF REMAINS UNCLEAR. CMD LEADS TO CHRONIC MYOCARDIAL ISCHEMIA, WHICH RESULTS IN AN INTRA-CARDIOMYOCYTE METABOLIC SHIFT TOWARDS INCREASED GLUCOSE UTILIZATION, REDUCED FREE FATTY ACID OXIDATION, AND TRIGLYCERIDE (TG) ACCUMULATION IN THE MYOCARDIUM – LEADING TO MYOCARDIAL STEATOSIS, WHICH WE HAVE ASSOCIATED WITH DIASTOLIC DYSFUNCTION, A PRE-HFPEF TRAIT. BECAUSE WOMEN WITH CMD ARE MORE LIKELY THAN MEN TO SUFFER CHRONIC ISCHEMIA FOR LONGER DURATIONS, OUR CENTRAL HYPOTHESIS IS THAT CMD-RELATED CHRONIC ISCHEMIA AND SUBSEQUENT MYOCARDIAL STEATOSIS ARE KEY CONTRIBUTORS TO THE DEVELOPMENT OF HFPEF IN WOMEN WITH CMD. EMERGING DATA FROM OUR GROUP UNDERSCORES THE IMPORTANCE OF CHRONIC INFLAMMATORY (I.E. EICOSANOID) PATHWAYS IN GOVERNING RESPONSES TO THE ISCHEMIC, INTRA-CARDIOMYOCYTE METABOLIC SHIFTS, AND CARDIAC MECHANICAL STRESSORS THAT HAVE BEEN IMPLICATED IN CMD AND HFPEF PATHOPHYSIOLOGY. THEREFORE, THE AIMS OF THIS EARLY STAGE INVESTIGATOR R01 APPLICATION ARE TO: (1) DETERMINE THE RELATIONSHIP BETWEEN CHRONIC ISCHEMIA AND MYOCARDIAL STEATOSIS AND THE EXTENT TO WHICH MYOCARDIAL STEATOSIS MEDIATES ASSOCIATIONS BETWEEN ISCHEMIA AND PRE-CLINICAL HFPEF IN CMD; AND, (2) IDENTIFY SPECIFIC EICOSANOID MOLECULES THAT UNDERLIE RISK FOR CMD-RELATED MYOCARDIAL STEATOSIS, PRE-CLINICAL HFPEF TRAITS, AND CLINICAL HFPEF. IN A PROSPECTIVE COHORT OF 220 CMD WOMEN UNDERGOING COMPREHENSIVE CARDIAC MAGNETIC RESONANCE (CMR) IMAGING AND SPECTROSCOPY, WE WILL DETERMINE CLINICAL HFPEF STATUS AND QUANTIFY: (I) MYOCARDIAL TG CONTENT AND STEATOSIS; (II) CHRONIC ISCHEMIA BURDEN, AND (III) PRE-CLINICAL CMR HFPEF TRAITS TO RELATE CHRONIC ISCHEMIA WITH MYOCARDIAL STEATOSIS. PLASMA BIOSAMPLES FROM THE COHORT WILL UNDERGO HIGH-THROUGHPUT ANALYSES TO IDENTIFY DISTINCT EICOSANOID PROFILES ASSOCIATED WITH MYOCARDIAL STEATOSIS. AN EXPLORATORY ANALYSIS WITH 18F-FDG PET WILL RELATE THE EICOSANOID PROFILES TO MYOCARDIAL-SPECIFIC INFLAMMATION. THE EICOSANOID PROFILES WILL ALSO BE TESTED FOR INCIDENT HFPEF IN A LARGE COMMUNITY COHORT WITH OVER A DECADE OF HFPEF OUTCOMES. UNDERSTANDING THE ROLE OF CARDIAC STEATOSIS WITH RESPECT TO CMD-RELATED ISCHEMIA, INFLAMMATION, AND HFPEF TRAITS PROMISES TO REVEAL NOVEL TARGETS FOR PREVENTING AND TREATING HFPEF, ESPECIALLY IN WOMEN.
assistance · Last action 2025-07-02
$3,202,489
Department of Health and Human Services
RANDOMIZED CONTROLLED TRIAL OF VIRTUAL REALITY FOR GI CANCER PAIN TO IMPROVE PATIENT REPORTED OUTCOMES - PROJECT SUMMARY PATIENTS WITH DIGESTIVE TRACT MALIGNANCY OFTEN EXPERIENCE SEVERE AND UNREMITTING ABDOMINAL PAIN THAT NEGATIVELY AFFECTS PHYSICAL, EMOTIONAL, AND SOCIAL FUNCTION, AS WELL AS HEALTH RELATED QUALITY OF LIFE (HRQOL). DESPITE THE SUBSTANTIAL BURDEN OF VISCERAL CANCER PAIN, AVAILABLE THERAPIES ARE LIMITED IN THEIR ABILITY TO OFFER SAFE AND EFFECTIVE ANALGESIA. PATIENTS FREQUENTLY TURN TO OPIOIDS WHEN OTHER TREATMENTS FAIL TO PROVIDE ADEQUATE ANALGESIA, YET OFTEN DISCOVER THAT OPIOIDS ALSO FALL SHORT IN DELIVERING MEANINGFUL PAIN REDUCTION OR IMPROVING HRQOL. FOR THOSE WHO DO ACHIEVE EFFECTIVE ANALGESIA FROM OPIOIDS, THEY NONETHELESS ASSUME A SUBSTANTIAL RISK OF OPIOID-RELATED MORBIDITY AND MORTALITY. FURTHER, IN MANY CASES, OPIOIDS IMPAIR BOWEL FUNCTION AND CAN WORSEN— NOT ALLEVIATE—ABDOMINAL PAIN. HENCE, THERE IS A CRITICAL GAP IN MANAGING VISCERAL PAIN FROM DIGESTIVE TRACT MALIGNANCIES; IT IS VITAL TO ADDRESS THIS EVIDENCE GAP IN A WAY THAT MAXIMIZES BENEFITS FOR PATIENTS WHILE MINIMIZING THE RISK OF HARM. THERAPEUTIC VIRTUAL REALITY (VR) HAS EMERGED AS A PROMISING AND EVIDENCE-BASED TREATMENT MODALITY FOR CANCER PAIN. USERS OF VR WEAR A PAIR OF GOGGLES WITH A CLOSE-PROXIMITY SCREEN IN FRONT OF THE EYES THAT CREATES A SENSATION OF BEING TRANSPORTED INTO LIFELIKE, THREE-DIMENSIONAL WORLDS. TO DATE, VR HAS BEEN LIMITED TO SHORT-TERM CLINICAL TRIALS FOR CANCER PAIN. MOREOVER, LIMITED RESEARCH EXISTS ON THEORY-BASED VR MODALITIES BEYOND MERE DISTRACTION, SUCH AS VR THAT EMPLOYS ACCEPTANCE AND COMMITMENT THERAPY (ACT) WITH COMPONENTS OF BIOFEEDBACK AND MINDFULNESS. TO BRIDGE THESE GAPS, THIS STUDY SEEKS TO: (1) ASSESS THE IMPACT OF IMMERSIVE VR ON PATIENT-REPORTED OUTCOMES (PROS), INCLUDING PAIN, ACTIVITY METRICS, AND OPIOID USE AMONG PATIENTS WITH VISCERAL PAIN FROM A DIGESTIVE TRACT MALIGNANCY; (2) ASSESS DIFFERENCES IN PROS, ACTIVITY METRICS, AND OPIOID USE BETWEEN SKILLS-BASED VR THERAPY VS. DISTRACTION VR THERAPY; AND (3) DETERMINE PATIENT-LEVEL PREDICTORS OF VR TREATMENT RESPONSE IN VISCERAL CANCER PAIN. TO ADDRESS THESE AIMS, THE STUDY WILL MEASURE PROS AND OPIOID USE IN 360 PATIENTS RANDOMIZED AMONG 3 GROUPS AND FOLLOW THEM FOR 60 DAYS AFTER ENROLLMENT: (1) AN ENHANCED VR GROUP RECEIVING SKILLS-BASED VR; (2) A DISTRACTION-BASED VR GROUP RECEIVING PATIENT-SELECTED VR VIDEOS; AND (3) A VR SHAM CONTROL GROUP USING A VR HEADSET WITH 2-D CONTENT. THE RESULTS WILL INFORM BEST PRACTICES FOR THE IMPLEMENTATION OF VR FOR VISCERAL CANCER PAIN MANAGEMENT AND GUIDE SELECTION OF PATIENT-TAILORED EXPERIENCES.
assistance · Last action 2026-02-12
$3,190,411
Department of Health and Human Services
ACE AND MYELOID CELL METABOLISM - A LONG SOUGHT GOAL OF MEDICAL RESEARCH IS TO IDENTIFY WAYS TO INCREASE THE EFFECTIVENESS OF THE IMMUNE RESPONSE. HERE, WE PRESENT A MEANS OF INCREASING MYELOID CELL FUNCTION BY INCREASING CELL EXPRESSION OF ANGIOTENSIN CONVERTING ENZYME (ACE). WE SHOW THAT 1) UNDER NATURAL CIRCUMSTANCES IN BOTH HUMANS AND MICE, MYELOID CELLS INCREASE THEIR PRODUCTION OF ACE IN RESPONSE TO IMMUNE CHALLENGE. THIS IS AN ADAPTIVE RESPONSE THAT ALLOWS THE CELLS TO BETTER RESPOND TO THE CHALLENGE. 2) WHEN THIS PROCESS IS EXAGGERATED BY USING GENETIC MEANS TO AUGMENT ACE EXPRESSION IN EITHER MACROPHAGES OR NEUTROPHILS, THE RESULT IS A MARKED INCREASE IN THE ABILITY OF MICE TO MOUNT BOTH AN INNATE AND ADAPTIVE IMMUNE RESPONSE AGAINST A VARIETY OF IMMUNE CHALLENGES. THIS INCREASE IN RESPONSE IS DIRECTLY DUE TO THE CATALYTIC ACTIVITY OF THE OVER-EXPRESSED ACE PROTEIN. 3) THE ENHANCED IMMUNE RESPONSE IS THE RESULT OF ACE-INDUCED METABOLIC CHANGES THAT INCREASE OXIDATIVE PHOSPHORYLATION AND INCREASE MYELOID CELL ATP. THIS IS QUITE DIFFERENT FROM THE WELL DESCRIBED MYELOID METABOLIC EFFECTS OF LPS. THAT ACE AFFECTS CELL LEVELS OF ATP IS A VERY NEW FINDING BASED ON MASS SPECTROMETRY AND CHEMICAL ANALYSIS OF ATP LEVELS IN TWO LINES OF MICE. IN CONTRAST, MYELOID CELLS GENETICALLY LACKING ACE HAVE REDUCED ATP AND REDUCED IMMUNE FUNCTION. 4) SIMILAR TO THE GENETIC ACE KO, ACE INHIBITORS (ACEI) REDUCE NEUTROPHIL SUPEROXIDE AND ANTI-BACTERIAL RESPONSE IN BOTH HUMANS AND MICE. THUS, THERE IS A DIRECT RELATIONSHIP BETWEEN THE LEVEL OF ACE EXPRESSION BY MYELOID CELLS, MYELOID CELL ATP CONTENT, AND EFFECTIVENESS OF THE IMMUNE RESPONSE. UNDERSTANDING HOW ACE AFFECTS MYELOID CELL IMMUNOMETABOLISM WILL REVEAL A TOTALLY NEW BIOCHEMICAL MEANS OF ENHANCING MYELOID FUNCTION THAT MIGHT ULTIMATELY BE MANIPULATED TO ENHANCE HUMAN RESPONSE. IN AIM 1, WE EXAMINE THE DETAILED METABOLISM OF MYELOID CELLS WITH INCREASED ACE EXPRESSION TO IDENTIFY CHANGES AFFECTING IMMUNE FUNCTION. IN AIM 2, WE WILL STUDY THE ROLE OF THE TRANSCRIPTION FACTOR PPARA IN INDUCING THE IMMUNE PHENOTYPE OF MYELOID CELLS EXPRESSING INCREASED ACE. WE ALSO ASK HOW ACE ACTIVITY INDUCES INCREASED CELL PPARA. IN AIM 3, WE STUDY WHETHER ACE ACTS AS AN AUTOCRINE OR PARACRINE FACTOR AND WHETHER WE CAN CHARACTERIZE THE PEPTIDE PRODUCT OF ACE RESPONSIBLE FOR AFFECTING CELL METABOLISM AND INCREASING THE IMMUNE RESPONSE OF MYELOID CELLS.
assistance · Last action 2026-01-31
$3,125,033
Department of Health and Human Services
PUSH-BUTTON CARDIAC MRI FOR NON-INVASIVE QUANTIFICATION OF MYOCARDIAL ENERGY CONSUMPTION IN HEART FAILURE - ABSTRACT CARDIAC ENERGY CONSUMPTION IS THE CENTRAL DETERMINANT OF CARDIAC FUNCTION. ITS IMPAIRMENT IS THE HALLMARK OF HEART FAILURE (HF), WHICH ACCOUNTS FOR NEARLY $40 BILLION IN MEDICAL COSTS EVERY YEAR AND IS THE MOST FREQUENT CAUSE OF HOSPITALIZATION. IN HF PATHOPHYSIOLOGY, THE DEPRESSION OF CONTRACTILE FORCE OF THE MYOCARDIUM IS NOT MATCHED BY A CONCOMITANT DEPRESSION OF ENERGY CONSUMPTION. THIS RESULTS IN THE UNCOUPLING BETWEEN MECHANICAL CONTRACTION AND ENERGY EXPENDITURE OF THE HEART, WHICH DRIVES SYSTOLIC OR DIASTOLIC DYSFUNCTION OF THE HEART. THUS, THE DETECTION OF EARLY ALTERATIONS IN CARDIAC ENERGETICS IN HF PATIENTS CAN PROVIDE CRITICAL INFORMATION ON HEART HEALTH AND GUIDE NOVEL THERAPEUTIC INTERVENTIONS FOR HF WHICH ARE UNDER DEVELOPMENT. SINCE THE HEART RELIES ALMOST EXCLUSIVELY ON AEROBIC OXIDATION, THE GOLD STANDARD FOR STAGING ALTERATIONS IN CARDIAC ENERGETICS IS FROM INVASIVELY MEASURED WHOLE HEART MYOCARDIAL OXYGEN CONSUMPTION (MVO2). HOWEVER, INVASIVE CATHETERIZATION IS NOT A PRACTICAL WAY FOR REPEAT SURVEILLANCE OF THE DISEASE IN THE SUSPECT POPULATION OR THE MONITORING OF THERAPEUTIC EFFICACY. HENCE THERE IS AN UNMET NEED FOR A NONINVASIVE APPROACH THAT CAN ENABLE REPEATABLE QUANTITATIVE ASSESSMENT OF CARDIAC ENERGETICS. SIGNIFICANT EFFORT HAS BEEN MADE TOWARDS DEVELOPING NONINVASIVE TECHNIQUES FOR MVO2 MEASUREMENT, PARTICULARLY BASED ON POSITRON EMISSION TOMOGRAPHY (PET) AND MAGNETIC RESONANCE SPECTROSCOPY (MRS). HOWEVER, THEY HAVE NOT MADE IT INTO THE CLINICAL ARENA DUE TO MAJOR TECHNICAL/PRACTICAL LIMITATIONS. AN ALTERNATIVE APPROACH, WHICH OVERCOMES KEY LIMITATIONS OF PET AND LONGSTANDING TECHNICAL CHALLENGES OF MRS FOR ESTIMATING MVO2, EMPLOYS MAGNETIC RESONANCE OXIMETRY. NONETHELESS, THIS REQUIRES SIMULTANEOUS AND RELIABLE MAPPING OF QUANTITATIVE MR PARAMETERS IN THE RAPIDLY MOVING CORONARY SINUS, WHICH IS NEARLY IMPOSSIBLE FOR THE CMR TECHNIQUES TODAY. HERE, WE PROPOSE TO DEVELOP AND VALIDATE A SINGLE, FAST, FREE-BREATHING, MOTION-INSENSITIVE ACQUISITION TO SIMULTANEOUSLY DERIVE CORONARY SINUS OXYGEN SATURATION AND MYOCARDIAL BLOOD FLOW FOR MVO2 MEASUREMENT. WE WILL TEST THE DEVELOPED METHOD IN DETECTING THE IMPAIRED CARDIAC ENERGY CONSUMPTION LEVEL IN AN ANIMAL MODEL WITH HEART FAILURE. THE PROPOSED METHOD IS EXPECTED TO QUANTIFY CARDIAC ENERGY CONSUMPTION NONINVASIVELY, WITHOUT IONIZING RADIATION, AND EXOGENOUS CONTRAST AGENTS. ACCORDINGLY, FORMING THE FOUNDATION TOWARD (1) EARLY DETECTION AND CLASSIFICATION OF HF FOR TARGET TREATMENTS, (2) PROGNOSIS OF HF WITHOUT INVASIVE PROCEDURES, AND (3) LONGITUDINAL MONITORING OF HF PROGRESSION TO GUIDE THE DEVELOPMENT OF NOVEL HF THERAPIES.
assistance · Last action 2025-08-27
$3,123,890
Department of Health and Human Services
RACIAL DIFFERENCES IN PROSTATE CANCER MOLECULAR SUBTYPING
assistance · Last action 2026-04-16
$3,099,234
Department of Health and Human Services
MAGNETOFLUORESCENT NANOPLATFORM FOR GLIOBLASTOMA THERAPY
assistance · Last action 2025-08-26
$3,067,561
Department of Health and Human Services
VACCINE INDUCED IMMUNE-INFLAMMATORY RESPONSE AND CARDIOVASCULAR RISK - PROJECT SUMMARY IN THE MIDST OF EMERGING THREATS FROM SPORADIC VIRAL ENTITIES, THE PERENNIAL INFLUENZA VIRAL STRAINS CONTINUE TO IMPOSE A SUBSTANTIAL BURDEN OF MORBIDITY AND MORTALITY THAT COMPOUNDS TOTAL ANNUAL RISKS TO THE POPULATION AT LARGE. LAST SEASON (2018-19), INFLUENZA AFFECTED 35.5 MILLION AND LED TO 490,600 HOSPITALIZATIONS AND 34,200 DEATHS IN THE U.S. THESE VITAL STATISTICS HAVE BEEN STEADILY RISING EACH YEAR. INDIVIDUALS WITH CARDIOVASCULAR DISEASE ARE ESPECIALLY SUSCEPTIBLE TO THE MORBIDITY AND MORTALITY ASSOCIATED COMMUNITY-ACQUIRED VIRAL INFECTIONS SUCH AS INFLUENZA. VACCINATION SIGNIFICANTLY REDUCES THE INCIDENCE OF CARDIOVASCULAR EVENTS AT THE POPULATION LEVEL; HOWEVER, ADMINISTRATION OF INFLUENZA VACCINATION AT THE INDIVIDUAL LEVEL IS EXTREMELY VARIABLE WITH RESPECT TO (I) THE EXTENT OF HUMORAL ANTIBODY RESPONSE ACHIEVED, AND (II) THE DEGREE OF CARDIOPROTECTION CONFERRED. INTRIGUINGLY, THE DEGREE OF CARDIOPROTECTION CONFERRED DOES NOT DEPEND ENTIRELY ON THE LEVEL OF HUMORAL IMMUNITY ACHIEVED, HIGHLIGHTING FURTHER OPPORTUNITIES TO DISCOVER AND DERIVE CLINICAL BENEFIT FROM A PREVENTIVE THERAPY WITH BOTH COMPLEX AND NON- UNIFORM EFFECTS. ACCUMULATING EVIDENCE NOW INDICATES THAT UPSTREAM MEDIATORS OF ENDOGENOUS IMMUNE- INFLAMMATORY PATHWAYS ARE LIKELY KEY DETERMINANTS OF THE INDIVIDUAL-LEVEL RESPONSE TO AND BENEFIT FROM AN ADMINISTERED VACCINATION. THESE MOLECULAR MEDIATORS OF SYSTEMIC IMMUNE-INFLAMMATORY ACTIVITY, TERMED EICOSANOIDS, INCLUDE A DIVERSE FAMILY OF SMALL BIOACTIVE LIPIDS THAT ARE ENZYMATICALLY DERIVED FROM POLYUNSATURATED FATTY ACIDS. BASED ON RESULTS FROM PRELIMINARY STUDIES, WE HYPOTHESIZE THAT SPECIFIC EICOSANOIDS NOT ONLY PREDICT THE IMMUNOLOGIC RESPONSE TO INFLUENZA VACCINATION BUT ALSO PREDICT ITS CONFERRED PROTECTION FROM ADVERSE CARDIOVASCULAR EVENTS, IRRESPECTIVE OF INFECTION STATUS. THEREFORE, WE PROPOSE AN ANCILLARY STUDY FOR THE NHLBI-FUNDED INFLUENZA VACCINE TO EFFECTIVELY STOP CARDIOTHORACIC EVENTS AND DECOMPENSATED HEART FAILURE (INVESTED) TRIAL, THAT AIMS TO: (1) IDENTIFY EICOSANOIDS THAT PREDICT THE CLASSIC HUMORAL ANTIBODY RESPONSE TO INFLUENZA VACCINATION IN PATIENTS WITH CHRONIC CARDIOVASCULAR DISEASE, WHO REPRESENT THE POPULATION SUBSET MOST AT-RISK FOR ADVERSE EVENTS; AND, (2) IDENTIFY EICOSANOIDS GENERATED IN RESPONSE TO VACCINATION THAT CORRESPOND WITH REDUCED RISK FOR CARDIOVASCULAR EVENTS, IRRESPECTIVE OF HUMORAL IMMUNITY AND INFECTION STATUS. THE EXISTING INFRASTRUCTURE OF THE INVESTED TRIAL OFFERS A COST-EFFECTIVE WAY TO REACH INDIVIDUALS WHO ARE AT THE HIGHEST RISK FOR INFLUENZA- ASSOCIATED EVENTS AND ENABLE A RIGOROUS STUDY DESIGN FOR INVESTIGATING HETEROGENEITY IN THE RESPONSE TO AND BENEFIT FROM VACCINATION.
assistance · Last action 2026-06-16
$2,998,175
Department of Health and Human Services
MECHANISMS FOR GH ACTION ON EPITHELIAL CELLS
assistance · Last action 2026-03-20
$2,986,029
Department of Health and Human Services
TRANSCENDING COVID-19 BARRIERS TO PAIN CARE IN RURAL AMERICA: PRAGMATIC COMPARATIVE EFFECTIVENESS TRIAL OF EVIDENCE-BASED, ON-DEMAND, DIGITAL BEHAVIORAL TREATMENTS FOR CHRONIC PAIN - PROJECT SUMMARY THE COVID-19 PANDEMIC HAS AFFECTED EVERYONE IN DIFFERENT WAYS. FOR PEOPLE FROM THE RURAL AMERICA WITH CHRONIC DISEASES, PARTICULARLY THOSE WHO EXPERIENCE PAIN, THE PANDEMIC CAN NOT ONLY WORSEN PAIN, BUT ALSO IT CAN TRIGGER ANXIETY, DEPRESSION, TROUBLE SLEEPING, AND SUBSTANCE USE. THIS PSYCHOLOGICAL DISTRESS IS EXACERBATED BY PHYSICAL AND SOCIAL ISOLATION, FEAR OF SEEKING IN-PERSON VISITS, AND DIMINISHED ABILITY TO ACCESS CLINICAL CARE DURING THE PANDEMIC. ONE WAY DOCTORS AND HEALTH SYSTEMS ARE REACHING OUT IS BY VIDEO VISITS, WHERE PATIENTS AND THEIR PROVIDERS COMMUNICATE ONLINE VIA THE INTERNET. HOWEVER, VIDEO VISITS STILL HAVE LIMITS. THEREFORE, WE CAN HELP SUPPORT THEM WITH OTHER TECHNIQUES. BEYOND VIDEO VISITS, THERE ARE HOME-BASED PROGRAMS THAT PATIENTS CAN ADMINISTER THEMSELVES TO HELP MANAGE THEIR PAIN. THESE PROVEN PROGRAMS CAN OVERCOME STAFFING SHORTFALLS, BE USED ACROSS LONG DISTANCE TO REACH ANYONE IN THE WORLD AND CAN BE USED AT THE TIME AND PLACE OF THE PATIENTS' CHOOSING. IN THIS STUDY, WE WILL COMPARE TWO AVAILABLE, EVIDENCE-BASED, DIGITAL TREATMENT PROGRAMS THAT PATIENTS CAN USE AT HOME. THE GOAL IS TO SEE IF ONE APPROACH IS BETTER THAN THE OTHER, AND WHETHER CERTAIN PATIENTS RESPOND TO ONE MORE THAN THE OTHER. THE FIRST PROGRAM IS AN APP THAT CAN RUN ON ANY SMARTPHONE OR COMPUTER. THE PROGRAM OFFERS AN 8-WEEK, AT-HOME CURRICULUM TO LEARN AND PRACTICE NEW SKILLS THAT CAN HELP MANAGE PAIN. THE PROGRAM RUNS ON A STANDARD SCREEN ON YOUR PHONE OR COMPUTER. THE SECOND PROGRAM IS ALSO A PROVEN, 8-WEEK PROGRAM, BUT IT USES A TECHNOLOGY CALLED VIRTUAL REALITY, OR VR. VR INVOLVES WEARING SPECIALIZED GOGGLES THAT CREATE A SENSATION OF BEING IN A 3D WORLD. EVIDENCE SHOWS THAT VIRTUAL WORLDS CAN HELP PEOPLE LEARN AND RETAIN NEW SKILLS THAT HELP REDUCE PAIN. THE STUDY WILL RECRUIT 300 PEOPLE FROM RURAL COMMUNITIES IN CALIFORNIA, LOUISIANA, AND ALABAMA AND RANDOMIZE THEM INTO EITHER THE 2D OR 3D PROGRAMS. WE WILL THEN FOLLOW PATIENTS FOR 8 WEEKS DAYS AND MEASURE THEIR PAIN LEVELS. WE WILL ALSO MEASURE SIGNS OF DISTRESS, INCLUDING CORONAVIRUS-RELATED ANXIETY, ALONG WITH MEASURING MEDICATIONS USED FOR PAIN, SUCH AS OPIOIDS, AND THE IMPACT OF PAIN ON OVERALL QUALITY OF LIFE. TO CONDUCT THE STUDY, WE WILL ASK PATIENTS TO PERIODICALLY COMPLETE SHORT SURVEYS ONLINE AND ALLOW PERMISSION FOR THE RESEARCH TEAM TO COLLECT INFORMATION FROM THE ELECTRONIC HEALTH RECORD. WE DEVELOPED THIS STUDY WORKING WITH PATIENT PARTNERS FROM THE AMERICAN CHRONIC PAIN ASSOCIATION (ACPA), AND THEY WILL BE PART OF THE RESEARCH TEAM THROUGHOUT THE CONDUCT, ANALYSIS, AND REPORTING OF THE STUDY. THE RESULTS WILL HELP PATIENTS, DOCTORS, AND HEALTH SYSTEM DECIDE HOW BEST TO ADMINISTER HOME-BASED, PATIENT-ADMINISTERED, DIGITAL TREATMENT PROGRAMS FOR PAIN, AND WILL OFFER RECOMMENDATION ON HOW TO SELECT THE RIGHT TREATMENT FOR THE RIGHT PATIENT.
assistance · Last action 2026-02-09
$2,982,292
National Aeronautics and Space Administration
IN-SPACE PRODUCTION OF STEM CELL THERAPIES
contract · Last action 2026-01-27
$2,930,391

Federal contract dollars to this establishment. Primary NAICS: 541715 - RESEARCH AND DEVELOPMENT IN THE PHYSICAL, ENGINEERING, AND LIFE SCIENCES (EXCEPT NANOTECHNOLOGY AND BIOTECHNOLOGY). Last action: 2026-01-27. Source: USAspending.gov, net obligations. Recipient address is the SAM registration / HQ address, not necessarily the worksite.

Inspection history

Date	Trigger	Violations	Serious	Penalty
2023-10-06	Complaint	0	—	$0
2023-03-27	Accident	1	—	$600
2022-08-29	Complaint	1	—	$935
2020-07-08	Fatality/Catastrophe	4	1	$21,700
2013-04-02	Planned	0	—	$0
2006-10-06	Accident	3	2	$18,710
2006-05-04	Complaint	0	—	$0
2005-07-13	Complaint	0	—	$0
1999-01-15	Complaint	1	1	$935
1998-09-21	Complaint	0	—	$0
1997-10-16	Complaint	0	—	$0
1997-06-09	Complaint	1	—	$280
1997-05-21	Complaint	0	—	$0
1996-06-26	Complaint	1	—	$0
1995-10-12	Complaint	0	—	$0
1993-06-18	Complaint	0	—	$0
1992-05-06	Complaint	1	—	$0
1991-07-18	Referral	0	—	$0
1990-09-26	Complaint	0	—	$0

Source: OSHA IMIS. Citation amounts reflect initially assessed penalties; final amounts after appeal may differ.

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