AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grant

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.

2020 Grantees

Sara J. Buhrlage, PhD

Sara J. Buhrlage, PhD

Assistant Professor 
Dana-Farber Cancer Institute 
Boston, Massachusetts 
Bivalent DUB recruiters for targeted protein stabilization

Research
Dr. Buhrlage is set to develop a novel class of agents, bivalent deubiquitinase (DUB) proximity inducing molecules, that can selectively stabilize targeted proteins. This new drug development paradigm is enabled by her group’s recent success in developing selective DUB ligands for several members of the enzyme family.

Biography
Dr. Buhrlage completed a PhD in organic chemistry in 2008 at the University of Michigan and trained for two years in medicinal chemistry at the Broad Institute. Prior to joining as a faculty member in 2015, Dr. Buhrlage ran the medicinal chemistry core laboratory at Dana-Farber. She is currently an assistant professor in Dana-Farber’s Cancer Biology Department and Harvard Medical School’s Biological Chemistry and Molecular Pharmacology Department. Her research group focuses on the development of small molecule modulators of deubiquitylating enzymes (DUBs) for cancer therapy.

Acknowledgment of Support
I’d like to sincerely thank the AACR and MPM for the opportunity to pursue this “high-risk, high-reward” research project. As an early career investigator, the chance to pursue this type of project could propel my career. We will pursue the research aggressively and are optimistic we’ll credential a new cancer treatment paradigm.   

Robert Eil, MD

Robert Eil, MD

Assistant Professor 
Oregon Health & Science University 
Portland, Oregon 
Targeting the ionic checkpoint on T cell antitumor function

Research
Resistance to cancer immunotherapy is common, owing to tumor induced T cell dysfunction. Dr. Eil’s work demonstrated for the first time that potassium (K+) is elevated within cancers and deters T cell antitumor functions (Eil et al, Nature 2016; Science 2019). In this project, he will test the hypothesis that cancer cell death suppresses T cell function through K+ sensitive signal transduction. He is set to 1) determine the functional significance of cancer cell death byproducts for inflammasome and T cell activation in human Intrahepatic Cholangiocarcinoma (ICC), 2) define the mechanism underlying K+ control of T cell function, and 3) assess the impact of interventions to reprogram T cell K+ transport as cancer immunotherapeutics.

Biography
Dr. Eil completed a research fellowship at the Surgery Branch of the National Cancer Institute during his surgical training, focusing on T cell biology and tumor immunology. Following his clinical fellowship in surgical oncology (MSKCC), he returned to Oregon Health & Science University with appointments in the Departments of Surgery and Cellular, Developmental and Cancer Biology. Dr. Eil is a surgeon-scientist focused on applying immunotherapy to cancers involving the liver, pancreas, and bile ducts. His multidisciplinary expertise provides a unique perspective on alleviating suppression of T cell function in cancer to improve the lives and outcomes of patients.

Acknowledgment of Support
Receipt of this 2020 AACR-MPM Oncology Transformative Cancer Research Grant represents a critical milestone in my development as an independent scientist. I am thrilled to have the opportunity to pursue this exciting line of investigation with the potential to apply ground-breaking immune-based treatments to patients with treatment-resistant cancers.

Hani Goodarzi, PhD

Hani Goodarzi, PhD

Assistant Professor 
University of California, San Francisco
San Francisco, California 
Discovering and targeting cancer-engineered pathways of metastasis 

Research
Given the current understanding of cancer progression as an evolutionary process, there is a largely unexplored possibility that cancer cells may engineer their own regulatory pathways. The discovery and characterization of such cancer-emergent regulatory mechanisms forms the foundation of the research proposed by Dr. Goodarzi and his team. Their recent discovery of orphan non-coding RNAs (oncRNAs) as a cancer-specific class of small RNAs with regulatory potential provides an opportunity for a systematic search for functional neo-regulators of gene expression in cancer cells. In addition to providing much needed insight into tumor evolution, this research also nominates novel targets that are solely active in cancer cells and whose targeted inhibition is unlikely to elicit on-target systematic toxicity.

Biography
With a dual background in computational and experimental cancer biology, Dr. Goodarzi brings a multidisciplinary approach to studying tumor progression. He is currently an assistant professor at the University of California, San Francisco. His research is focused on developing strategies that enable an unbiased search for previously unknown pathways of metastasis. By developing novel technologies for genome-wide measurement of hard-to-quantify RNA molecules, he has made key discoveries about the role of oncRNA, tRNAs, and tRNA fragments in cancer metastasis. On the computational front, he is focused on building network analytical models that help elucidate key pathways and processes that drive human disease.

Acknowledgment of Support
The AACR-MPM Transformative Cancer Research Grant provides a unique opportunity for my team to tackle a high-risk, high-reward project. In addition to providing support and resources, this represents a vote of confidence in our approach from the leaders in the field.

2019 Grantees

Liron Bar-Peled, PhD

Liron Bar-Peled, PhD

Assistant Professor
Massachusetts General Hospital
Boston, Massachusetts
Deciphering the mechanisms of ferroptosis signaling and death in cancer

Research
Induction of ferroptosis (FO), a cell death pathway mediated by oxidative stress, may be a successful therapeutic approach for the treatment of multiple forms of cancer. Although high levels of lipid peroxides can trigger FO, little is known about how lipid peroxides signal and induce FO. Dr. Bar-Peled aims 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 FO induction.

Biography
Dr. Bar-Peled received his PhD in biology from the Massachusetts Institute of Technology. As a Damon Runyon postdoctoral fellow at the Scripps Research Institute, he focused on the response of cancer cells to oxidative stress. He is currently an assistant professor at 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.

Sahand Hormoz, PhD

Sahand Hormoz, PhD

Assistant Professor
Dana-Farber Cancer Institute
Boston, Massachusetts
Reconstructing the differentiation dynamics and genealogy of cancer cells

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.

Biography
Dr. Hormoz obtained his PhD in applied physics at Harvard University. His postdoctoral studies were conducted jointly as a theorist at the Kavli Institute of Theoretical Physics (UCSB) and as an experimental systems and synthetic biologist 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.