This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) will support research by The General Hospital Corporation (doing business as Massachusetts General Hospital) to investigate the use of chemical "degrader" tools that target specific chromatin regulators critical for the survival and proliferation of multiple myeloma cells. The $623,120 award will fund two specific aims: 1) assessing the comparative consequences of inhibiting versus degrading the CBP and P300 chromatin regulators in multiple myeloma cells using epigenomic, transcriptomic, and chromatin conformation assays; and 2) determining the optimal dosing and drug combinations required for CBP/P300 degraders to induce tumor regression in multiple myeloma xenograft models. The research aims to reveal mechanisms of gene regulatory dysfunction in multiple myeloma, describe the effects of a drug currently under preliminary clinical investigation, and nominate a promising new class of chemical degraders as potential therapeutics for this deadly disease. The project will be conducted at Massachusetts General Hospital from March 1, 2025 to February 28, 2030.
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