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.”

2022 Grantees

Research

Metastasis is a complex multi-step process, during which, tumor cells must profoundly alter their metabolism to adapt to the differing environments they encounter. Although metastatic seeding of specific organ sites can predict disease severity and patient prognosis, the molecular logic underlying when and to which organ a tumor cell will metastasize remains unclear. Dr Perera’s lab is set to explore the metabolic features within the primary tumor that define which secondary tissue a metastatic cell will ultimately colonize. Using innovative mouse models that enable metabolite profiling of tumor cells and their organelles, Dr Perera aims to discover master regulators that promote metastasis, and manipulate these drivers to disable the aggressive features of metastatic pancreatic ductal adenocarcinoma.   

Biography

Rushika M. Perera PhD is the recipient of the NIH Director’s New Innovator Award, the Damon Runyon-Rachleff Innovation Award, the AACR NextGen Star Award and the 2021 Gunter Blobel Early Career Award of the American Society for Cell Biology. She is currently an Associate Professor in the School of Medicine at the University of California, San Francisco. Her research program seeks to understand how metabolic organelles such as the lysosome contribute to cellular plasticity and adaptation to stress, with a focus on pancreatic cancer.

Acknowledgement of Support

The AACR-MPM Transformative Cancer Research Grant provides us with a unique opportunity to pursue a new line of research at the interface of cell biology, metabolism and cancer biology. I am incredibly grateful to the AACR and MPM for supporting our ideas and research goals.

Research

Mutant transcriptional machineries have been found to form transcriptional condensates. While wild type nucleophosmin1 (NPM1) forms liquid-liquid phase separation (LLPS) at the nucleolus, mutant NPM1 (NPM1c) moves to the cytoplasm and forms smaller puncta dots in the nucleus. Dr. Zhang and his research group uncovered a neomorphic, transcriptional-amplifier function of NPM1c on chromatin that sustains a pathogenic leukemia transcription program. With this AACR grant, they seek to use state-of-art comprehensive approaches to address the fundamental question of transcriptional dysregulation in cancer.

Biography

Dr. Xiaotian Zhang obtained his Bachelor’s degree in Biological Sciences from Fudan University in Shanghai. He obtained his Ph.D. in Molecular Human Genetics at Baylor College of Medicine. After a stint at the Van Andel Institute for a three-year special fellowship, he was appointed as a research investigator in the University of Michigan. Dr. Zhang is currently a tenure-track assistant professor in the Department of Biochemistry and Molecular Biology at the University of Texas Health Science Center at Houston.

Acknowledgement of Support

I want to thank AACR and MPM Oncology Charitable Foundation for the Transformative Cancer Research Grant, on behalf of a team that consists of a cancer biologist and biophysicist. This award will greatly enhance the existing collaboration of this exciting team that is focused on the condensate formed by mutant NPM1 in acute myeloid leukemia.