The AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grants support early- to mid-career investigators employing highly innovative approaches to major problems or challenges in cancer research. Funded projects are expected to have a potentially transformative impact on future clinical practice.

2024 grantees

Research

Histone mutant diffuse midline gliomas (DMGs) are propelled by developmentally stalled glial progenitors that remain in a state of “stemness” instead of differentiating to glial lineages. Recently, a specific class of semi-essential (diet-derived) lipids were found to alter chromatin architecture and drive differentiation of these progenitors in vitro and in vivo. Dr. Danial aims to determine how these lipids work by identifying their direct protein targets and downstream effectors using two complementary discovery approaches. First, proteomics/chemoproteomics technologies will be undertaken to identify the direct protein targets of these lipids. Second, CRISPR screens will be conducted to identify gene products that are required for the pro-differentiation effect of these lipids.

Biography

Dr. Danial received an undergraduate degree in Biological Sciences from Stanford University, and a doctoral degree in Molecular, Cellular and Biophysical Studies from Columbia University. Her postdoctoral studies at Dana-Farber Cancer Institute focused on the role of BCL-2 family proteins, where she discovered a molecular link between cell survival/death regulatory pathways and metabolism. She is currently an Associate Professor of Medicine at the Dana-Farber Cancer Institute (DFCI), Harvard Medical School. Her laboratory investigates the role of nutrient utilization patterns and metabolic signaling in physiology and disease.

Acknowledgment of Support

“This award will catalyze high-risk, high-reward studies with great potential for conceptual and technical innovation in glioma-inhibitory lipid-protein interactions that regulate chromatin states, an untapped area of discovery in metabolic signaling. The results from these studies may have implications for broader set of cancers that involve stalled/dysregulated differentiation.”

Research

CAR T cells and T cell-targeting immunotherapies such as anti-PD-1 show limited success in solid tumors, including the vast majority of colorectal cancers. T cells cannot function in isolation, but instead engage in positive and negative feedback loops with other immune and non-immune cells. Dr. Pelka previously discovered several conserved, spatially organized multicellular interaction networks that shape immune responses in human tumors. Using a new framework to systematically perturb these immune hubs, she now aims to (1) reveal cancer cell-derived signals that influence immune hub landscapes and (2) discover CAR T cell payloads that induce anti-tumor immunity hubs in currently unresponsive colorectal tumors. This work is expected to expose new and powerful therapeutic levers to promote anti-tumor responses.

Biography

Dr. Pelka pursued her doctoral training at the Institute of Innate Immunity at the University of Bonn in Germany. As a postdoctoral fellow at the Broad Institute of MIT and Harvard, she shifted her interest to cancer immunology and systems biology and led a large single-cell RNA sequencing and spatial profiling effort on human colorectal cancer. She is currently an assistant investigator at the Gladstone-UCSF Institute of Genomic Immunology, an assistant professor in the Department of Microbiology and Immunology at University of California San Francisco, and an investigator at the Parker Institute for Cancer Immunotherapy.

Acknowledgment of support

“The AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grant is enabling my lab to pursue a bold and risky approach very early during my independent career. If successful, this work will vastly accelerate new discoveries towards better immunotherapies and transform my lab’s research for many years to come.”