All Cancers

Current Projects
Benjamin M. Stinson, PhD

Dr. Stinson studies the mechanism of non-homologous end joining (NHEJ), the primary method used by our cells to repair DNA double strand breaks (DSBs), a particularly toxic form of DNA damage in which a single piece of DNA is completely broken into two pieces. He is examining how the NHEJ machinery modifies DNA at DSBs to allow re-joining of the DNA molecule. This work will contribute to our knowledge of cancer development and treatment, as defects in NHEJ result in predisposition to cancer, and a number of common cancer treatments introduce DSBs that are primarily repaired by NHEJ.

Project title: "Mechanism of DNA processing during non-homologous end joining"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Johannes C. Walter, PhD, and Joseph L. Loparo, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Anthony D. Sung, MD

We share our bodies with trillions of microorganisms: the microbiota. The microbiota interacts with our bodies to affect health and disease, including cancer development and response to therapies. For example, in patients receiving hematopoietic stem cell transplantation as treatment for leukemias, lymphomas, and other blood cancers, disruptions in the microbiota have been linked to disease relapse, infections, treatment complications, and survival. Given these serious effects, it is important to understand how to manipulate the microbiota through therapies like prebiotics: carbohydrates that can be ingested to stimulate the growth and maintenance of various bacteria. The challenge is that different people have different microbiotas and therefore may respond differently to the same prebiotic. To address this challenge, Drs. David and Sung have developed a novel microfluidic platform to isolate individual bacteria from a patient’s stool sample and grow them against selected prebiotics, allowing an understanding of how a given patient’s microbiota may respond to different prebiotics. To do this using conventional techniques would take a stack of petri dishes as tall as the Empire State Building and months of work; their innovative system can do it in a single day. They believe that by using this novel system, they will be able to predict the best prebiotic for a given patient, thereby manipulating their microbiota and improving cancer outcomes. They will test this strategy using patient samples in their artificial gut “bioreactor” as well as in mouse models. The success of this project would lead to clinical trials of personalized prebiotics.

Project title: "Personalized prebiotics to optimize microbiota metabolism and improve transplant outcomes"
Institution: Duke University
Award Program: Innovator
Cancer Type: Blood, All Cancers
Research Area: Microbiology
Shaogeng (Steven) Tang, PhD

Dr. Tang is interested in discovering small-molecule inhibitor drugs that target human immune-checkpoint proteins, including programmed cell death protein 1 (PD-1), using a combination of biochemistry, protein engineering, structural biology and immunology approaches. These small-molecule inhibitors would offer safety advantages resulting from their much shorter half-lives as compared to FDA-approved monoclonal antibody therapies, and possibly also offer efficacy advantages resulting from increased penetration and distribution within the tumor microenvironment. His work has broad implications for the development of a novel methodology for small-molecule drug discovery and the design of new cancer immunotherapies. 

Project title: "Toward small-molecule inhibitors against human immune checkpoint PD-1"
Institution: Stanford University
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Peter S. Kim, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Iva Tchasovnikarova, PhD

Dr. Tchasovnikarova is investigating the role of chromatin remodeling in epigenetic gene silencing by the recently discovered HUSH complex. Her research aims to delineate how heterochromatin formation is achieved through the concerted action of heterochromatin-associated proteins, heterochromatic histone modifications, and ATP-driven chromatin remodeling. As heterochromatin formation has been shown to be associated with oncogenic events, her future work will define general principles that could be exploited to design cancer therapies aimed at heterochromatin dysregulation.

Project title: "Deciphering the role of chromatin remodeling in epigenetic repression by the HUSH complex"
Institution: Massachusetts General Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Robert Kingston, PhD
Cancer Type: All Cancers
Research Area: Chromatin Biology
Sophia Tintori, PhD

Dr. Tintori is studying nematode worms from Chernobyl, Ukraine, to investigate the biological effects of continuous radiation exposure. While ionizing radiation is known to cause cancer, little is known about the levels that increase health risks or how animals adapt to high radiation environments. Dr. Tintori is comparing worms from Chernobyl, the area with the highest known levels of background radiation on the planet, to similar animals that have not been exposed. This research may shed light on specific challenges presented by radiation and possible biomolecular defenses.

 
Project title: "Mechanisms of radiation tolerance in Caenorhabditis from Chernobyl"
Institution: New York University School of Medicine
Award Program: Fellow
Sponsor(s) / Mentor(s): Matthew Rockman, PhD
Cancer Type: All Cancers
Research Area: Basic Genetics
Eliezer M. Van Allen, MD

Many cancers are treated with chemotherapies that affect DNA repair, such as platinum chemotherapy, and some patients derive significant benefit from these agents. However, the underlying genomic features that drive selective response to these treatments is incompletely characterized. Dr. Van Allen aims to blend precision cancer medicine principles with DNA repair treatments and enhance cancer care. He will do so by studying the genomics of response to existing and emerging DNA repair therapies in preclinical models as well as patients across different tumor types.

Project title: "Dissecting response to conventional and emerging DNA damage and repair therapies"
Institution: Dana-Farber Cancer Institute
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Geoffrey I. Shapiro, MD, PhD
Cancer Type: All Cancers
Research Area: Computational Biology
Jonathan G. Van Vranken

Dr. Van Vranken is focusing on the metabolic alterations associated with human cancers. In order to support normal physiology, all cells must obtain nutrients from the environment and allocate them toward both the production of energy and synthesis of cellular building blocks. Cancer cells often reprogram their metabolism to support the uncontrolled growth associated with tumors. Dr. Van Vranken is using mass spectrometry-based approaches to investigate the mechanisms underlying the changes in cellular metabolism. His research will shed light on how metabolites interact with the proteome (all the proteins in a cell) to support cell growth and proliferation.

Project title: "Systematic identification of metabolite-protein interactions in human cells"
Institution: Harvard Medical School
Named Award: The Mark Foundation for Cancer Research Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Steven Gygi
Cancer Type: All Cancers
Research Area: Proteomics
Alexandra-Chloé Villani, PhD

Immune checkpoint inhibitors unleash the immune system to attack tumors; they have revolutionized the treatment of solid cancers by changing the prognosis for many patients, improving their quality of life and offering long-lasting remission. However, these immunotherapies can also spur assaults on healthy organs called “immune-related adverse events” (irAEs), ranging from minor rashes and fevers to severe gastrointestinal complications and deadly heart inflammation. Dr. Villani is analyzing patient samples using state-of-the-art genomic technologies and integrative immunological approaches to understand why and how these irAEs occur in cancer patients. Ultimately, she aims to identify therapeutic solutions to prevent or clinically manage irAEs without reducing the lifesaving potential of immunotherapy.

Project title: "Deciphering the Achilles' heel of cancer immunotherapy"
Institution: Massachusetts General Hospital
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Immunotherapy
Linda T. Vo, PhD

Dr. Vo focuses on T cell-based cancer immunotherapy, such as chimeric antigen receptor “CAR” T cells, as a transformative therapeutic approach. While recent studies have demonstrated the efficacy of CAR-T cell therapy in treating certain leukemias and lymphomas, further advancements are required to broaden its therapeutic utility. Pluripotent stem cells (PSCs) have the capacity to generate any cell type of the body and represent a potentially inexhaustible source of clinically useful cells. Using a novel strategy to promote the continuous generation of T cell progenitors from PSCs, she will engineer “off-the-shelf” T cells with improved tumor-recognition capability from stem cells. The successful generation of potent, dual-antigen specific T cells from PSCs in large quantities as an off-the-shelf product would be invaluable to the widespread application of T cell-based immunotherapies.

Project title: "Off-the-shelf T cells from human pluripotent stem cells with precise tumor recognition using combinatorial antigen-sensing circuits"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Jeff A. Bluestone, PhD
Cancer Type: All Cancers
Research Area: Immunotherapy
Lexy von Diezmann, PhD

Dr. von Diezmann studies how cells control the pathways used to repair DNA. Errors in DNA repair contribute to the development of many cancers, such as breast, ovarian, and pancreatic cancers. Dr. von Diezmann will explore the basic principles governing the DNA damage response by examining how a specific subtype of homologous repair enzymes functions in reproductive cells of the model organism C. elegans. Her project will provide mechanistic insight into how changes in the liquid-like organization of proteins at sites of DNA damage regulate repair, supporting the development of novel chemotherapies that modulate the DNA damage response.

Project title: "State changes of a liquid-like compartment monitor crossover recombination"
Institution: University of Utah
Named Award: The Mark Foundation for Cancer Research Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Ofer Rog, PhD, and Erik Jorgensen, PhD
Cancer Type: All Cancers
Research Area: Chromosome and Telomere Biology
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