Damon Runyon News

A unifying hallmark of several types of cancer is the uncontrolled fragmentation of mitochondria, the microscopic compartments that generate energy for the cell. Although many key players have been implicated in this process, the manner in which these factors assemble to modify the mitochondrial architecture and induce the unrestricted fragmentation associated with cancer is unknown. Dr. Grotjahn [Nadia's Gift Foundation Innovator] uses cutting-edge instrumentation, powerful electron microscopes, and pioneering image processing techniques to visualize this process inside cancer cells.

The human adaptive immune system continuously surveils for proteins and protein fragments that do not belong. Mutated protein fragments in tumor cells, called neoantigens, form a basis by which the adaptive immune system discriminates between cancer and healthy cells. Delivered therapeutically, neoantigens specific to a tumor can similarly serve as anti-tumor vaccines. Dr. Weinstein has developed a new imaging modality that simultaneously identifies new genetic mutations and physically maps interactions between the cells that possess them.

Dr. Fang [HHMI Fellow] develops multiplexed imaging techniques to illuminate how enhancers control gene expression at a single cell level. Enhancer alterations are widely spread in cancer, but there is limited understanding of how these enhancers vary between single cells and relate to oncogene expression. Dr. Fang will generate single-cell regulatory networks to investigate how enhancer activities are disrupted in IDH-mutant cancers. The proposed work may help identify enhancer-based therapeutic targets for cancer treatment in the future.

Dr. Gao [The Mark Foundation for Cancer Research Fellow] studies how the tumor microenvironment influences anti-tumor immune responses. Her research focuses on lipid metabolism in cytotoxic T lymphocytes (CTLs), a specialized population of white blood cells that kill malignant cells. To defend against this attack, tumors release lipid metabolites that can incapacitate infiltrating CTLs. Consequently, these metabolites create an immunosuppressive environment and promote tumor progression. Dr. Gao aims to unravel the pathways utilized by these harmful lipids.

Dr. Cote is exploring embryonic development to better understand how cells cooperate and build complex tissues. Since cancer cells often erroneously redeploy developmental programs and behaviors, her research into how neighboring cells align will yield insights into how cancerous cells metastasize and invade other tissues. Dr.

Dr. Park studies the interplay between the way chromatin is folded inside the nucleus and the role it plays in epigenetic regulation that creates cellular memory. Abnormal epigenetic regulation causes a broad range of diseases, including cancer. Using super-resolution imaging of chromatin structure, single-cell sequencing methods, and genetic approaches, Dr. Park aims to define the functional role of higher-order 3D chromatin organization in epigenetic memory regulations at single-nucleus resolution.

Dr. Jarjour is searching for novel methods to overcome resistance to immunotherapy. While immunotherapies have had a transformative impact for some patients suffering from specific cancers, some tumors are highly resistant to these treatments. These resistant tumors often lack the majority of immune cell types that could potentially attack the tumor. Dr. Jarjour is addressing this problem by developing antigen-independent methods to stimulate the innate proliferative capacity of tissue-resident CD8+ T cells, based on signaling molecules called cytokines.

Dr. Sulkowski [HHMI Fellow] investigates how solid tumors exist within dynamic microenvironments. Tumor cells hijack cell-to-cell communication mechanisms to interact with one another and their host to promote their growth. Dr. Sulkowski will study VHL deficient clear-cell renal cell carcinoma, the most common form of kidney cancer with more than 400,000 annual diagnoses worldwide. He will mechanistically investigate a novel phenomenon of active histone H3 secretion by cancer cells.

Dr. McClune [HHMI Fellow] investigates plant biosynthesis of therapeutic compounds. Approximately half of FDA-approved chemotherapeutics, including first line drugs like paclitaxel (Taxol) and vinblastine (Velban), derive from the arsenal of defensive chemicals that plants synthesize. Unfortunately, both the discovery of new plant-derived therapies and their scalable production are limited by intrinsic challenges of plant biology and genomics. Dr. McClune is developing systematic methods for identifying the biosynthetic pathways plants use to produce defensive molecules.

Dr. Unlu studies how cancer cells adapt to nutrient limitations in their environment. High metabolic demands of proliferating cancer cells create metabolic bottlenecks for in vivo growth within solid tumors. Dietary and pharmacological interventions could provide unique opportunities to target such metabolic liabilities. However, studying tumor metabolism in vivo adds many layers of biological complexity, meaning these potential targets are currently poorly characterized. Dr.