AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grant
The AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grants are an exciting funding initiative to stimulate “high-risk, high-reward” research from early- to mid-career investigators. This grant mechanism is intended to promote and support creative, paradigm-shifting cancer research that might not be funded through conventional channels. It is expected that these grants will catalyze significant scientific discoveries that will advance our understanding of cancer and have a potentially transformative impact on future clinical practice.
Scientific Statement of Research
The overarching goal of this project is to illuminate how ferroptosis (FO), a cell death pathway mediated by oxidative stress, is sensed within cancer cells and the mechanisms by which cancer cells succumb to FO. There is strong evidence that induction of FO may be a successful therapeutic approach for the treatment of multiple forms of cancer. Lipid peroxides are physiologically important signaling and damaging molecules that at high levels trigger FO. Despite their profound basic importance and potential clinical benefit, surprisingly little is known about how lipid peroxides signal and induce FO. Dr. Bar-Peled proposes to develop and employ highly innovate proteomic and metabolomic technologies to test the hypothesis that lipid peroxide modification of proteins is a mechanism for signal transduction and promotes FO.
Dr. Bar-Peled received his PhD in biology from the Massachusetts Institute of Technology, where he used advanced cellular and molecular techniques to uncover how nutrients are sensed by the mTORC1 pathway. In 2013, he joined the laboratory of Ben Cravatt to understand how cancer cells respond to oxidative stress. Employing novel chemical, proteomic, and biochemical approaches, he revealed new druggable components of the NRF2 antioxidant response pathway, uncovering new mechanisms by which NRF2 regulates metabolic pathways. In early 2019, Dr. Bar-Peled joined the Center for Cancer Research at the Massachusetts General Hospital and the Department of Medicine at Harvard Medical School.
Acknowledgment of Support
It is a tremendous honor to be awarded this prestigious grant. We are now emboldened to undertake creative and cutting-edge research to address fundamental biochemical mechanisms by which cancer cells adapt to metabolic stress. The goal is to translate these basic discoveries into therapeutic insights for cancer patients.
Scientific Statement of Research
In a subtype of blood cancers called myeloproliferative neoplasms (MPN), the same mutation can result in drastically different disease phenotypes in different patients. This disconnect between genotype and phenotype is partly because the same mutation can have different consequences depending on the identity of the hematopoietic cell in which the mutation first occurs and the extent to which the population of mutated cells expands. Dr. Hormoz aims to 1) identify the disease-initiating cancer stem cell and characterize its differentiation dynamics in patients by sequencing the full transcriptome and the cancer mutations of individual cells and 2) reconstruct the genealogy of the cancer cells (and infer the history of disease progression) in patients from the pattern of accrued somatic mutations in individual cancer cells. This proposal will answer some of the most fundamental questions about where MPN originates and how it manifests itself in each patient.
Dr. Hormoz obtained his undergraduate degree in engineering science from the University of Toronto. He then completed his SM and PhD in applied physics at Harvard University with Michael Brenner. His postdoctoral studies were conducted jointly as a theorist at the Kavli Institute of Theoretical Physics (UCSB) with Boris Shraiman and as an experimental systems and synthetic biologist in the lab of Michael Elowitz at Caltech. Currently, he is an assistant professor with the Department of Data Sciences at the Dana-Farber Cancer Institute and the Department of Systems Biology at Harvard Medical School.
Acknowledgement of Support
I am thrilled to be a recipient of this AACR-MPM grant and to work closely with the AACR. This award recognizes the importance of innovative research and gives my lab the freedom to tackle fundamental questions in blood cancers using creative and risky approaches that otherwise would not be possible.