Project Grant K99GM155610
- This Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) provides $125,000 to the Dana-Farber Cancer Institute, Inc. to conduct research on transcriptional regulation by the ZMYM2-KDM1A-CoREST complex. The goal of this 2-year project (12/18/2024 - 11/30/2026) is to gain a structural understanding of how the ZMYM2 transcription factor recruits the KDM1A-CoREST chromatin modifying complex to...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, is providing $127,145 to The Trustees of Princeton University to conduct research dedicated to unraveling the regulatory mechanisms governing chromatin organization and gene transcription during neural development in the Drosophila model organism. The primary focus is on understanding how...
- This Project Grant award of $147,486 was provided by the National Institute of General Medical Sciences (NIGMS), under the Biomedical Research and Research Training federal grant program (CFDA 93.859), to The Trustees of the University of Pennsylvania for the period of January 1, 2025 to June 30, 2026. The goal of this research project is to investigate the distinct molecular roles of Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2) and upstream factors in establishing silencing at...
- This Project Grant award from the National Institutes of Health (NIH) under the Trans-NIH Research Support program (CFDA 93.310) supports research to visualize the mechanisms at the intersection of chromatin, transcription, and epigenetics. The $1,525,500 award to Harvard Medical School aims to develop a combinatorial biochemical and structural approach called "Visual Biochemistry" that uses a fully reconstituted chromatin transcription system and time-resolved single-particle...
- This Project Grant from the National Institutes of Health's National Cancer Institute, under the Cancer Biology Research program (CFDA 93.396), provides $900,000 to Midwestern University from September 2022 through August 2025. The grant funds research to characterize novel protein-protein interactions within Polycomb Repressive Complex 1 (PRC1) and investigate their role in the selective assembly of functionally distinct PRC1 complexes. PRC1 epigenetically regulates chromatin and improper...
- This Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower) provides $135,594.00 to The Leland Stanford Junior University to develop novel pharmacological approaches to rewire oncogenic gene expression and induce cancer cell death. The primary objectives are to: Develop small molecule chemical inducers of proximity (CIPs) that can potently activate pro-apoptotic gene expression and kill aggressive leukemias driven by MLL gene translocations. This will...
- This $789,739 Project Grant award from the National Human Genome Research Institute (CFDA 93.172 - Human Genome Research) supports research conducted by the Sloan-Kettering Institute for Cancer Research to develop experimental and computational tools that extend the Perturb-seq platform. The goal is to systematically reconstruct diverse transcriptional states in vitro, with a focus on fibroblasts, using combinatorial genetic perturbations. Key activities include establishing an iterative...
- This two-year, $1,204,512 National Science Foundation project grant supports research into the robustness and adaptability of the dynamic epigenome through a multiscale approach. Funded under the Biological Sciences program (CFDA 47.074), the award to Brandeis University involves investigating the fundamental rules that guide adaptive epigenetic changes in cells without alterations to the genetic blueprint. The research utilizes high-resolution imaging, microfluidics, and automated culture...
- This Project Grant award from the National Cancer Institute's Cancer Research Manpower program (CFDA 93.398) provides $151,040 in funding to St. Jude Children's Research Hospital Inc. to elucidate the role of an essential transcription factor in SWI/SNF-mutant rhabdoid tumors. The research aims to characterize the function of this poorly understood transcription factor and its interaction with a repressive chromatin-regulatory complex in the unique cellular environment resulting from the loss of...
- This Project Grant award from the National Science Foundation's Mathematical and Physical Sciences program (CFDA 47.049) provides $200,000 to The Johns Hopkins University to conduct research on "Defining Barriers to Nucleosome Mobility Through Single-Molecule Manipulation". The research aims to understand how nucleosomes, the DNA-protein structures that package chromosomes, can spontaneously slide along DNA and be actively moved by cellular enzymes called chromatin remodelers. This...
UNRAVELING THE DYNAMIC COMPETITION BETWEEN ACTIVATING AND REPRESSIVE COMPLEXES IN SHAPING CHROMATIN ACCESSIBILITY - PROJECT SUMMARY CHROMATIN ACCESSIBILITY PLAYS A CRITICAL ROLE IN DETERMINING THE GENE EXPRESSION PROGRAMS THAT UNDERLIE CELLULAR FATES AND FUNCTIONS IN DEVELOPMENT AND DISEASE. CONSERVED CHROMATIN MODIFYING COMPLEXES, SUCH AS POLYCOMB-GROUP (PCG) AND TRITHORAX-GROUP (TRXG) PROTEINS, ARE BELIEVED TO ENGAGE IN A COMPETITIVE PROCESS TO SET EITHER REPRESSED OR ACCESSIBLE CHROMATIN STATES, RESPECTIVELY. MUTATIONS IN THESE MULTIPROTEIN COMPLEXES ARE KNOWN TO CAUSE A WIDE RANGE OF DISEASES, INCLUDING DEVELOPMENTAL DISORDERS AND CANCERS. HOWEVER, THE PRECISE MOLECULAR MECHANISMS THAT GOVERN THE COMPETITION BETWEEN REPRESSIVE AND ACTIVATING COMPLEXES FOR THE ESTABLISHMENT, MAINTENANCE, OR ALTERATION OF CHROMATIN ACCESSIBILITY REMAIN LARGELY UNEXPLORED. THIS K99/R00 PATHWAY TO INDEPENDENCE AWARD PROPOSAL SEEKS TO DEFINE THE MECHANISMS AND DYNAMICS THAT SHAPE THE COMPETITION BETWEEN THE POLYCOMB REPRESSIVE COMPLEX 1 (PRC1) AND THE ACTIVATING CHROMATIN REMODELER MSWI/SNF FOR CHROMATIN ACCESSIBILITY IN HEALTH AND DISEASE CONTEXTS. THE CANDIDATE FOR THIS AWARD, DR. STEFAN NIEKAMP, IS A BIOPHYSICIST WITH EXPERIENCE IN MICROSCOPY AND BIOCHEMISTRY. HE TRAINED IN THE LABORATORY OF DR. RONALD VALE AT THE UNIVERSITY OF CALIFORNIA - SAN FRANCISCO, WHERE HE DETERMINED THE CONFORMATIONAL DYNAMICS OF THE MICROTUBULE-BASED MOTOR PROTEIN DYNEIN. DURING HIS POSTDOCTORAL STUDIES IN DR. ROBERT KINGSTON'S LABORATORY AT THE MASSACHUSETTS GENERAL HOSPITAL, HE HAS ESTABLISHED A TRACTABLE SINGLE-MOLECULE ASSAY WHICH PROVIDES A UNIQUE PERSPECTIVE WITH UNPRECEDENTED SPATIOTEMPORAL RESOLUTION TO DERIVE KINETIC MODELS AND TO DETERMINE THE SEQUENCE OF EVENTS DURING TRANSITIONS BETWEEN CHROMATIN STATES. COMBINING THIS RECONSTITUTION APPROACH WITH CELLULAR SUPER-RESOLUTION MICROSCOPY AND CUTTING-EDGE GENOMIC APPROACHES, THAT THE CANDIDATE WILL LEARN DURING THE MENTORED PHASE, THIS WILL PROVIDE A POWERFUL SYSTEM TO DISCERN THE MOLECULAR BASIS OF CHROMATIN ACCESSIBILITY REGULATION BY THE COMPETITION OF CHROMATIN MODIFYING COMPLEXES. TO OBTAIN THESE SKILL SETS, DR. NIEKAMP WILL WORK WITH WORLD RENOWNED EXPERTS IN THE FIELDS OF TRANSCRIPTIONAL REGULATION, GENOMICS, AND SUPER-RESOLUTION IMAGING AT HARVARD UNIVERSITY. IN ADDITION, THE CANDIDATE WILL TAKE A SUITE OF COURSES TO ADVANCE HIS PROFESSIONAL DEVELOPMENT. TOGETHER, THIS PROJECT WILL (I) DEFINE THE ROLES OF PRC1 COMPOSITION IN ORGANIZING CHROMATIN AND REGULATING GENE REPRESSION (AIM 1), DETERMINE HOW REPRESSIVE AND ACTIVATING COMPLEXES COMPETE TO CONTROL CHROMATIN STRUCTURE TRANSITIONS (AIM 2), AND IDENTIFY THE MOLECULAR MECHANISMS OF CANCER MUTATIONS IN DISRUPTING THE BALANCE BETWEEN REPRESSIVE AND ACTIVATING COMPLEXES (AIM 3). THE SUCCESSFUL EXECUTION OF THIS PROPOSAL WILL EQUIP THE CANDIDATE WITH A SUITE OF INTERDISCIPLINARY SKILL SETS IN BIOPHYSICS, CELL BIOLOGY, AND GENETICS WHICH WILL PROVIDE A ROBUST PLATFORM TO LAUNCH HIS CAREER AS AN INDEPENDENT RESEARCHER TO DECIPHER THE MOLECULAR BASIS OF TRANSCRIPTION REGULATION.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $125.0k | 7/14/25 | ||
| Not listed | $125.0k | 7/24/24 |