SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH

KUKXRCZ6NZC2

6X133

2026-05-14

2025-05-16

2002-02-25

6X133

Active

Non-Manufacturer

2025-05-16

2030-05-16

2026-05-14

MATTHEW WARSHAW

75N91022P00804

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AWARD

PURCHASE ORDER

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0.00

Department of Health and Human Services

2022-09-26

EXTEND SERVICES FOR THE PURCHASE ORDER: PURCHASE ORDER - SAMPLES FOR NCI'S MULTI-ANCESTRY GENOME-WIDE ASSOCIATION STUDY.

541380: TESTING LABORATORIES AND SERVICES

Q301: REFERENCE LABORATORY TESTING

75N92019P00092

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PURCHASE ORDER

-0.04

-0.04

-0.04

Department of Health and Human Services

2019-04-04

NIAMS' AUTOIMMUNITY BRANCH (AB) IS IN NEED OF A SCIENTIFIC INVESTIGATOR WITH A PHD IN BIO-SCIENCES TO CONCLUDE THE STUDY ON FAS MODULATION, CELL FATE AND ITS RELATION TO HUMAN DISEASE.

541990: ALL OTHER PROFESSIONAL, SCIENTIFIC, AND TECHNICAL SERVICES

R499: SUPPORT- PROFESSIONAL: OTHER

75N92018P00076

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246768.00

246768.00

246768.00

Department of Health and Human Services

2018-09-18

177LU-EB-DOTATATE IND ENABLEMENT PROJECT, SEE ATTACHED STATEMENT OF WORK FOR DETAILS.

621511: MEDICAL LABORATORIES

B504: SPECIAL STUDIES/ANALYSIS- CHEMICAL/BIOLOGICAL

2025-05-30

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Department of Health and Human Services

MOLECULAR MECHANISMS OF PROTEIN FUNCTION - PROJECT SUMMARY: THE GOALS OF THIS RESEARCH PROGRAM ARE TO UNDERSTAND THE MOLECULAR MECHANISMS UNDERLYING PROTEINS AND PROTEIN COMPLEXES THAT FACILITATE INTRACELLULAR ION TRANSPORT AND ENSURE GENOMIC INTEGRITY BY REPLICATING AND REPAIRING THE GENOME. FOR PROTEINS INVOLVED IN MEMBRANE TRANSPORT, WE AIM TO ELUCIDATE THE MECHANISMS BY WHICH IONS ARE RECOGNIZED AND TRANSPORTED ACROSS THE MEMBRANE AS WELL AS HOW THE ACTIVITIES OF THESE PROTEINS ARE REGULATED. FOR THOSE INVOLVED IN MAINTAINING GENOMIC INTEGRITY, WE WILL ADDRESS HOW GENOMIC FEATURES ARE RECOGNIZED TO RECRUIT THE REPLICATION AND REPAIR MACHINERIES TO SPECIFIC GENOMIC LOCI. WE EMPLOY A HIGHLY COLLABORATIVE APPROACH, COMBINING HIGH-RESOLUTION STRUCTURE DETERMINATION, ELECTROPHYSIOLOGY, IN VITRO RECONSTITUTION, CELL BIOLOGY, COMPUTATIONAL ANALYSIS AND MOUSE MODELS TO ESTABLISH A HOLISTIC UNDERSTANDING OF THESE PROTEINS AND PROTEIN COMPLEXES AT THE MOLECULAR LEVEL AND THEIR HOW DYSREGULATION CAN LEAD TO DISEASE. WE ARE CURRENTLY FOCUSED ON INVESTIGATING FOUR FAMILIES OF ION TRANSPORT PROTEINS INCLUDING THE LYSOSOMAL POTASSIUM AND PROTON CHANNEL TMEM175, THE CLC FAMILY OF CHLORIDE CHANNELS AND TRANSPORTERS, THE INOSITOL TRISPHOSPHATE RECEPTORS AND CLN7. TMEM175 IS A LYSOSOMAL CHANNEL RESPONSIBLE FOR MAINTAINING LYSOSOMAL PH THAT IS CRITICAL FOR LYSOSOMAL FUNCTION AND HOMEOSTASIS. WE ARE IDENTIFYING NOVEL INHIBITORS OF TMEM175 TO BETTER UNDERSTAND ITS PHYSIOLOGICAL ROLES AND DETERMINING HOW DIVERSE STIMULI COORDINATE TO REGULATE ITS ACTIVITY. HUMANS EXPRESS 5 CLC TRANSPORTERS IN THE ENDOLYSOSOMAL SYSTEM, WHERE THEY REGULATE ION AND PH HOMEOSTASIS. WE ARE ELUCIDATING HOW LIPIDS, ACCESSORY SUBUNITS AND OTHER STUMULI REGULATE THE ACTIVITY OF CLCS. INOSITOL TRISPHOSPHATE RECEPTORS ARE TETRAMERIC CHANNELS THAT RELEASE CA2+ STORED IN THE ENDOPLASMIC RETICULUM TO STIMULATE DIVERSE CELLULAR PATHWAYS INCLUDING FERTILIZATION, CELL DEATH AND CELL DIVISION. WE AIM TO UNDERSTAND HOW IP3RS ARE REGULATED BY THEIR DIVERSE STIMULI AND HOW THESE REGULATORY STIMULI RESULT IN CA2+ OSCILLATIONS. CLN7 IS A LYSOSOMAL CHLORIDE CHANNEL THAT MORE CLOSELY RESEMBLES TRANSPORTERS THAN CHANNELS. WE ARE INVESTIGATING HOW CLN7 CAN SELECTIVELY PERMEATE CHLORIDE IONS IN THE LYSOSOME. GENOMIC INTEGRITY REQUIRES THAT THE GENOME BE DUPLICATED DURING EACH CELL CYCLE WITHOUT ERRORS. WE ARE INVESTIGATING HOW DNA STRUCTURES, SUCH AS A G4-QUADREPLEXES ACT AS IMPEDIMENTS TO THE DNA REPLICATION MACHINERY AND HOW THESE IMPEDIMENTS CAN BE OVERCOME TO COMPLETE REPLICATION. COLLECTIVELY, THESE STUDIES WILL REVEAL INSIGHTS INTO PROTEIN FUNCTION THAT WILL IMPROVE UNDERSTANDING OF THEIR ROLES IN CRITICAL PHYSIOLOGICAL PROCESSES. AS DYSREGULATION OF ANY OF THESE COMPONENTS CAN LEAD TO DISEASE, THESE STUDIES WILL ALSO PROVIDE INSIGHTS INTO THE MOLECULAR BASIS OF DISEASE.

534160.00

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2025-05-28

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Department of Health and Human Services

INTERFERON E AS A TUMOR SUPPRESSOR AND POTENTIAL THERAPEUTIC IN PANCREATIC CANCER - PROJECT SUMMARY/ ABSTRACT LOSS OF CHROMOSOME 9P21.3 IS THE MOST COMMON HOMOZYGOUS DELETION ACROSS CANCERS, INCLUDING PANCREATIC DUCTAL ADENOCARCINOMA (PDAC), AND IT IS STRONGLY LINKED TO POOR PROGNOSIS AND INCREASED RESISTANCE TO IMMUNE CHECKPOINT BLOCKADE (ICB). 9P21.3 DELETIONS INVARIABLY AFFECT THE TUMOR SUPPRESSOR GENES CDKN2A/B, YET OFTEN INCLUDE A LINKED CLUSTER OF TYPE I INTERFERON (IFN) GENES, WHICH ENCODE CYTOKINES WITH ANTIVIRAL, ANTIPROLIFERATIVE, AND IMMUNE MODULATORY EFFECTS. WHILE OFTEN OVERLOOKED, OUR LABORATORY RECENTLY FOUND THAT CO-DELETION OF THE ENTIRE TYPE I IFN CLUSTER CONTRIBUTES TO AN IMMUNOSUPPRESSIVE MICROENVIRONMENT, LEADING TO REDUCED IMMUNE SURVEILLANCE, INCREASED METASTASIS, AND RESISTANCE TO ICB IN MOUSE MODELS OF PDAC. PRELIMINARY DATA SUGGEST THAT CO-DELETION OF IFNE, THE TYPE I IFN GENE CLOSEST TO CDKN2A/B, IS SUFFICIENT TO DISRUPT TUMOR IMMUNE SURVEILLANCE AND PROMOTE METASTASIS. THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO UNDERSTAND THE ROLE, REGULATION, AND THERAPEUTIC POTENTIAL OF IFNE IN PDAC IMMUNE SURVEILLANCE. AIM 1: DETERMINE THE SPECIFIC CONTRIBUTIONS OF IFNE TO TUMOR IMMUNE SURVEILLANCE. I WILL DECISIVELY ASSESS IF IFNE IS A TUMOR SUPPRESSOR IN THE CONTEXT OF CDKN2A LOSS BY EVALUATING THE EFFECTS OF IFNE DELETION IN ORTHOTOPIC PDAC MOUSE MODELS BY MEASURING TUMOR GROWTH, METASTASIS, AND IMMUNE INFILTRATES. I WILL ALSO TEST RECOMBINANT IFNE (RIFNE) AS A POTENTIAL THERAPY. AIM 2: CHARACTERIZE THE REGULATION OF IFNE DURING PDAC TUMOR PROGRESSION. I WILL PROFILE IFNE EXPRESSION IN PDAC AND THE TUMOR MICROENVIRONMENT AND WILL TEST THE HYPOTHESIS THAT IFNE IS INDUCED EARLY DURING TUMOR DEVELOPMENT BY MUTANT KRAS SIGNALING. TRAINING PLAN: I WILL WORK WITH AN INTERDISCIPLINARY TEAM OF MENTORS AND COLLABORATORS TO GAIN EXPERTISE IN CANCER BIOLOGY, MOLECULAR AND CELL BIOLOGY, AND IMMUNOLOGY. THE SKILLS THAT I WILL DEVELOP OVER THE COURSE OF THIS PROJECT WILL PREPARE ME FOR A CAREER AS AN INDEPENDENT RESEARCHER.

49538.00

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0.00

2025-05-28

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Department of Health and Human Services

INVESTIGATING THE ROLE OF MUTAGENIC DNA REPAIR DURING THE PERSISTENCE OF CANCER CELLS - PROJECT SUMMARY/ABSTRACT OUR CELLS POSSESS MULTIPLE MECHANISMS FOR REPAIRING DNA TO SAFEGUARD OUR GENOMES. WHILE PREDOMINANTLY ERROR-FREE PATHWAYS SUCH AS HOMOLOGOUS RECOMBINATION (HR) ARE RESPONSIBLE FOR MAINTAINING GENOMIC INTEGRITY, LOW-FIDELITY REPAIR MECHANISMS SUCH AS NON-HOMOLOGOUS END JOINING (NHEJ) CONTRIBUTE TO GENOMIC PLASTICITY. WHEN CELLS ARE UNDER EXTREME STRESS, SUCH AS BEING EXPOSED TO ANTI-CANCER DRUGS, THEY ENTER A STATE OF PERSISTENCE WHERE LOW-FIDELITY DNA POLYMERASES ARE UPREGULATED AND HR IS DOWNREGULATED, SHIFTING DEPENDENCE OF DNA REPAIR TO ERROR-PRONE MECHANISMS. IF MUTATIONS OCCUR IN GENES TARGETED BY THE ANTI-CANCER DRUG, THEY CAN RESULT IN ACQUIRED DRUG RESISTANCE AND LEAD TO CANCER RELAPSE. IN BRCA1/2-MUTANT CANCERS, WHICH ARE HR-DEFICIENT, INITIAL TUMOR RESPONSE TO DNA-DAMAGING POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS IS MITIGATED BY REVERSION MUTATIONS THAT RESTORE BRCA1/2 FUNCTION AND THEREFORE HR. THESE RESISTANCE-CONFERRING REVERSION MUTATIONS ARE OFTEN FLANKED BY REGIONS OF MICROHOMOLOGY, SUGGESTING THE INVOLVEMENT OF THE MUTAGENIC DNA REPAIR PATHWAY, MICROHOMOLOGY-MEDIATED END JOINING (MMEJ). IN COLORECTAL CANCER (CRC), INITIAL TUMOR RESPONSE TO EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) BLOCKADE IS MITIGATED BY ACQUIRED RESISTANCE-CONFERRING POINT MUTATIONS IN EGFR, KRAS, AND OTHER GENES. AS SUCH, UNDERSTANDING PERSISTENCE AND MUTAGENIC DNA REPAIR IS CRITICAL FOR STUDYING AND TREATING CANCER. HOWEVER, THE SPECIFIC MECHANISMS THAT PROMOTE MUTAGENIC DNA REPAIR AND DRIVE ACQUIRED DRUG RESISTANCE IN PERSISTER CANCER CELLS REMAIN UNCLEAR. WE HYPOTHESIZE THAT CELLULAR STRESS INDUCED BY ANTI-CANCER DRUGS REWIRES DNA REPAIR PATHWAYS IN PERSISTER CANCER CELLS, INCREASES THEIR RELIANCE ON MUTAGENIC DNA REPAIR—BY MMEJ—AND DRIVES THE EMERGENCE OF ACQUIRED RESISTANCE MUTATIONS. THIS PROPOSAL DESCRIBES WORK TO DEFINE THE ROLE OF MMEJ IN PERSISTENCE-MEDIATED ACQUIRED RESISTANCE IN CANCER CELLS BY (1) INVESTIGATING PERSISTENCE IN RESPONSE TO PARPI TREATMENT OF BRCA1/2 CANCER CELLS; (2) EXAMINING MECHANISMS OF MUTAGENIC DNA REPAIR IN PERSISTER COLORECTAL CANCER CELLS; AND (3) USING HIGH-CONTENT MICROSCOPY TO DETERMINE A MORPHOLOGICAL SIGNATURE OF PERSISTENCE. GIVEN THE CLINICAL IMPORTANCE OF PERSISTENCE IN CANCER, THIS WORK HAS THE POTENTIAL TO DIRECTLY IMPACT CANCER TREATMENT BY IDENTIFYING POTENTIAL THERAPEUTIC TARGETS, PARTICULARLY REGULATORS OF MMEJ, THAT COULD REDUCE PERSISTENCE-MEDIATED RELAPSE. LEVERAGING THE SPONSOR’S, AGNEL SFEIR’S, EXPERTISE IN DNA DAMAGE REPAIR AND COMMITMENT TO MENTORSHIP, ANNE CARPENTER’S SUPPORT OF THE MORPHOLOGICAL PROFILING COMPONENT, AND THE TRAINING INSTITUTION’S, SLOAN KETTERING INSTITUTE’S, EXTENSIVE NETWORK OF CORE FACILITIES, CANCER-FOCUSED SEMINARS, AND COMMITMENT TO SUPPORTING POSTDOCTORAL FELLOWS, THIS TRAINEE AND PROJECT ARE WELL-POSITIONED FOR SUCCESS. TOGETHER, THESE INVESTIGATIONS WILL PROVIDE A THOROUGH AND SYSTEMATIC EVALUATION OF DNA REPAIR AND MORPHOLOGY IN PERSISTENCE WHILE PREPARING THE TRAINEE FOR A CAREER AS AN INDEPENDENT RESEARCHER.

80702.00

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0.00

2025-05-30

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Department of Health and Human Services

UNDERSTANDING MECHANISMS OF IMPAIRED IMMUNITY IN THE AML BONE MARROW - PROJECT SUMMARY/ABSTRACT IMMUNE-BASED TREATMENTS FOR ACUTE MYELOID LEUKEMIA (AML), AN AGGRESSIVE HEMATOLOGIC MALIGNANCY THAT REMAINS FATAL FOR OVER HALF OF THE 20,000 PATIENTS DIAGNOSED IN THE UNITED STATES ANNUALLY, REMAIN AN UNMET CLINICAL NEED. THE IMPETUS TO USE T CELL-BASED IMMUNOTHERAPY APPROACHES FOR AML TREATMENT IS UNDERSCORED BY THE CURATIVE POTENTIAL OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR AML, ARISING FROM IMMUNE- MEDIATED GRAFT-VERSUS-LEUKEMIA ACTIVITY OF DONOR T CELLS, AND BY EMERGING CORRELATIVE DATA BETWEEN THE IMMUNE LANDSCAPE AND AML TREATMENT EFFICACY. UNDERSTANDING MECHANISMS OF INEFFECTIVE ANTI-LEUKEMIC T CELL ACTIVITY IN THE AML BONE MARROW (BM), THE SITE WHERE AML EMERGES, IS FUNDAMENTAL FOR ADVANCING IMMUNOTHERAPEUTIC APPROACHES FOR AML. OUR PRELIMINARY DATA HIGHLIGHT THE IMMUNOSUPPRESSIVE NATURE OF T CELLS WITHIN THE AML BM, THE DYNAMIC EVOLUTION OF T CELL CLONES WITH REGARD TO STATES OF T CELL ACTIVATION AND EXHAUSTION, AND THE IMMUNOMODULATORY POTENTIAL OF MALIGNANT AML CELLS ON T CELLS. WE HYPOTHESIZE THAT BOTH MALIGNANT AND NON-MALIGNANT CELLS IN THE AML BM PROMOTE IMPAIRED T CELL IMMUNITY, LEADING TO DISTINCT T CELL COMPOSITIONS AT DIFFERENT DISEASE STATES. THIS CAREER DEVELOPMENT PROGRAM WILL ADDRESS TWO SPECIFIC AIMS: (1) DETERMINE T CELL INTRINSIC FEATURES THAT AFFECT THE RELATIONSHIP BETWEEN T CELL PHENOTYPE, REPERTOIRE, AND DISEASE STATUS IN THE AML BM, AND (2) UNDERSTAND MECHANISTICALLY HOW MALIGNANT (AML BLASTS) AND NON-MALIGNANT CELLS IN THE AML BM SHAPE FEATURES OF THE T CELL COMPARTMENT. THE CANDIDATE HAS DEVELOPED THIS PROPOSAL AS AN EXTENSION OF HER ONGOING T CELL STUDIES IN HEMATOLOGIC MALIGNANCIES AND CLINICAL EXPERIENCE IN AML. DURING THE AWARD PERIOD, SHE WILL COMPLETE HER RESEARCH WITH CLOSE COUNSEL FROM HER PRIMARY MENTOR, OMAR ABDEL-WAHAB, MD, AN ACCOMPLISHED SCIENTIST IN LEUKEMIA BIOLOGY AND GENOMICS WHO IS THE CHAIR OF THE MSK MOLECULAR PHARMACOLOGY PROGRAM. ADDITIONAL INPUT WILL BE OFFERED BY HER CO-MENTOR, MARCEL VAN DEN BRINK, MD, PHD, AN INTERNATIONAL EXPERT IN T CELL BIOLOGY IN HEMATOLOGIC MALIGNANCIES, AND BY HER ADVISORY COMMITTEE. DRS. ABDEL-WAHAB AND VAN DEN BRINK ARE BOTH MENTORS WITH OUTSTANDING RECORDS OF NAVIGATING PHYSICIAN–SCIENTISTS TOWARD RESEARCH INDEPENDENCE. UNDER THEIR GUIDANCE, THE CANDIDATE WILL DEVELOP SKILLS THAT ARE CRITICAL FOR HER FUTURE LABORATORY PROGRAM, INCLUDING LEARNING TO GENERATE AND ANALYZE SYNGENEIC MOUSE MODELS OF AML, TO BUILD UPON HER KNOWLEDGE OF FUNCTIONAL STUDIES WITH PRIMARY AML SAMPLES, AND TO ADVANCE HER COMPUTATIONAL AND BIOINFORMATICS ABILITIES IN SEQUENCING-BASED IMMUNOLOGIC TECHNIQUES. COMPLETION OF THIS PROPOSAL WILL PROVIDE THE CANDIDATE WITH THE TRAINING AND MENTORSHIP REQUIRED TO CULTIVATE AND REFINE HER EXPERTISE IN T CELL IMMUNOLOGY AND LEUKEMIA RESEARCH AND TO ESTABLISH HER ACADEMIC CAREER AS AN INDEPENDENT LABORATORY-BASED CLINICAL INVESTIGATOR DEDICATED TO ADVANCING IMMUNOLOGIC TREATMENTS FOR AML.

607242.00

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0.00

2025-05-28

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Department of Health and Human Services

MECHANISMS OF P53 ENGAGEMENT AND ACTION AT THE BENIGN-TO-MALIGNANT TRANSITION IN SPORADIC TUMORIGENESIS - PROJECT SUMMARY THE TRANSCRIPTION FACTOR P53 IS ONE OF THE MOST CRITICAL BARRIERS TO TUMORIGENESIS. P53 IS MUTATED IN OVER HALF OF ALL HUMAN TUMORS, AND P53-MUTANT TUMORS TYPICALLY CARRY A WORSE PROGNOSIS. AS A TUMOR SUPPRESSOR, P53 APPEARS TO ACT AT THE TRANSITION FROM BENIGN TO MALIGNANT DISEASE, PREVENTING TRANSFORMATION OF CELLS THAT HAVE ALREADY ACQUIRED SOME PRO-TUMOR FEATURES, SUCH AS ONCOGENE ACTIVATION OR DNA DAMAGE. DECADES OF RESEARCH HAVE SOUGHT TO IDENTIFY WHAT MAKES P53 A POTENT TUMOR SUPPRESSOR, AS SUCH KNOWLEDGE COULD INFORM EFFECTIVE STRATEGIES FOR CANCER PREVENTION AND TREATMENT. THIS RESEARCH HAS SHOWN THAT P53 CAN BE ACTIVATED BY A VARIETY OF SIGNALS, AND IN TURN ACTIVATED P53 CAN REGULATE A WIDE VARIETY OF CELLULAR PROCESSES, INCLUDING CELL SURVIVAL, SENESCENCE, GENOMIC STABILITY, AND PLASTICITY. HOWEVER, THE INDUCERS AND ACTIONS OF P53 VARY WITH CONTEXT, AND THERE IS STILL NO CONSENSUS ON WHAT SIGNALS ENGAGE P53 DURING EARLY NEOPLASIA AND WHAT BIOLOGICAL PROGRAMS ARE MOST IMPORTANT FOR ITS TUMOR-SUPPRESSIVE FUNCTIONS. FURTHERMORE, WE STILL DO NOT KNOW THE KEY EVENTS FOLLOWING P53 LOSS THAT ENABLE TRANSITION TO MALIGNANCY. ATTEMPTS TO GAIN THIS KNOWLEDGE HAVE BEEN HAMPERED BY A LACK OF TOOLS TO DIRECTLY STUDY P53 IN THE SPECIFIC CELLS UNDERGOING TRANSFORMATION WITHIN ENDOGENOUS CONTEXTS. TO ADDRESS THESE GAPS IN KNOWLEDGE, WE WILL STUDY THE EVENTS SURROUNDING P53 ACTIVATION AND LOSS DURING THE INITIATION OF PANCREATIC DUCTAL CARCINOMA (PDAC), AN AGGRESSIVE CANCER IN WHICH P53 LOSS—WHICH OCCURS IN 70% OF PDACS—ENABLES PROGRESSION FROM BENIGN PRECURSOR LESIONS TO FULL-BLOWN CANCER. WE RECENTLY DEVELOPED NEW MOUSE MODELS OF PDAC THAT ALLOW US TO “SEE” P53 IN ACTION AS CELLS PROGRESS THROUGH THE BENIGN-TO-MALIGNANT TRANSITION. AMONG THE PREMALIGNANT PANCREAS CELLS, WE DISCOVERED A SUBPOPULATION THAT SHARES MANY TRANSCRIPTIONAL FEATURES WITH ESTABLISHED TUMOR CELLS, AND THUS THESE CELLS APPEAR TO BE TRANSITIONING FROM PREMALIGNANT TO MALIGNANT. THESE TRANSITIONING CELLS ARE ALSO THE CELLS WITH THE STRONGEST P53 ACTIVATION, AND SO THEY PROVIDE A UNIQUE OPPORTUNITY TO STUDY P53 ENGAGEMENT AND TUMOR-SUPPRESSIVE FUNCTION AT THE BENIGN-TO-MALIGNANT TRANSITION. USING SINGLE-CELL TRANSCRIPTIONAL AND SPATIAL ANALYSES, NEW COMPUTATIONAL APPROACHES TO INFER CELL STATE TRANSITIONS, AND OUR WELL-ESTABLISHED PLATFORM FOR RAPID GENETIC PERTURBATIONS IN VIVO, WE WILL DEFINE THE CELL-INTRINSIC AND CELL-EXTRINSIC EVENTS THAT LEAD TO THIS P53-ACTIVE TRANSITIONING CELL STATE. FURTHERMORE, WE WILL INVESTIGATE THE MECHANISMS BY WHICH ACTIVATED P53 SUPPRESSES NEOPLASTIC TRANSFORMATION IN THE TRANSITIONING CELLS, AS WELL AS THE EVENTS THAT INFLUENCE CANCER INITIATION IMMEDIATELY FOLLOWING P53 LOSS. THIS PROJECT WILL PROVIDE NOVEL INSIGHT INTO THE MECHANISMS THAT DRIVE PDAC INITIATION AND PROVIDE A DIRECT AND DETAILED CHARACTERIZATION OF P53 IN ACTION IN ENDOGENOUS CONTEXTS. GIVEN THE HIGH PREVALENCE OF TP53 MUTATIONS IN HUMAN CANCERS, WE EXPECT THE INSIGHTS INTO TUMORIGENESIS TO BE APPLICABLE TO MANY CANCER TYPES.

2159255.00

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