All Cancers

Current Projects
Jens C. Schmidt, PhD

The telomerase enzyme adds repetitive DNA sequences to the ends of human chromosomes, assuring genome integrity and providing unlimited proliferative potential to continuously dividing cells. Importantly, 90% of all cancers require telomerase activity for their survival. Mutations that activate the expression of telomerase reverse transcriptase (TERT), the major protein subunit of telomerase, are the most frequent mutations in a number cancers and are strongly correlated with poor clinical outcomes for patients carrying them. Telomerase is therefore an attractive target to potentially treat a wide range of aggressive cancers. Dr. Schmidt has developed techniques to study telomerase trafficking in vivo, as well as single-molecule assays to analyze telomerase catalysis and its modulation in vitro. He is able to visualize enzymatic action of telomerase in real-time at nucleotide resolution. He aims to understand the enzymatic mechanism of telomerase catalysis to identify potential weaknesses that can be targeted to inhibit telomerase action in cancer cells.

Project title: "Single-molecule analysis of telomerase recruitment to telomeres"
Institution: Michigan State University
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Biochemistry
Jan P. Schuemann, PhD

Though radiation therapy is a key treatment for many solid tumors, healthy surrounding tissue can be damaged through inadvertent exposure leading to serious side effects. Dr. Schuemann aims to establish if “extreme dose rate (EDR) proton therapy” can be used to spare healthy tissue while treating solid tumors. With new EDR technology, proton radiation therapy is delivered extremely fast—whole treatments in milliseconds. However, the mechanism underlying the reduction in side effects is still unknown. This research will focus on gastrointestinal irradiations but has the potential to be applied to nearly all cancer types. These results may demonstrate how EDR treatments can greatly improve radiation therapy outcome.

Project title: “Using extreme dose rates to protect healthy tissue in proton radiation therapy”
Institution: Massachusetts General Hospital
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Experimental Therapeutics
Esen Sefik, PhD

Dr. Sefik is examining the connection between obesity, cancer and the microbiome. An estimated 600 million people worldwide suffer from obesity, with 15-20% of deaths from cancer in the US alone linked to obesity. Recent studies in mice highlight the importance of intestinal bacteria and immune cells in obesity and colorectal cancer; however, these roles are not yet well characterized in humans. She will   analyze how high fat diet and obesity-associated intestinal bacteria change intestinal immunity in mice that harbor the human immune system and the human microbiota. This will help resolve some of the existing discrepancies and discover new players that are relevant to obesity and cancer in humans and help engineer better-targeted, combined therapies to colorectal cancer, especially in cases where existing immunotherapy fails.

Project title: "The effect of microbes, diet on the intestinal immune system in the context of obesity"
Institution: Yale University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Richard A. Flavell, PhD
Cancer Type: Colorectal, All Cancers
Research Area: Basic Immunology
Jason M. Sheltzer, PhD

Dr. Sheltzer studies how aneuploidy, or having too many or too few chromosomes in the cell, affects cancer development and treatment. Approximately 55% of breast cancers have an extra copy of one part (called the “q arm”) of chromosome 1. His lab is developing cutting-edge chromosome engineering technology to eliminate the extra copies of 1q from breast cancer cell lines and determine whether this prevents the cells from forming tumors. Additionally, they will test whether aneuploidy causes ovarian cancer cells to be sensitive to any chemotherapies, with the goal of identifying a drug that specifically kills cells with extra copies of chromosome 1q without affecting normal cells. These experiments could lead to highly effective “chromosome-specific” therapies based on aneuploidy.

Project title: “Are cancers addicted to aneuploidy?”
Institution: Cold Spring Harbor Laboratory
Award Program: Innovator
Cancer Type: Gynecological, Colorectal, Sarcoma, All Cancers
Research Area: Chromosome and Telomere Biology
Jianjin Shi, PhD

Dr. Shi [Layton Family Fellow] is exploring how cells die in the nervous system in both healthy and disease states. He will focus on a novel and ill-defined form of cell death in the nerve cells and nerve fibers upon injury or stress. Resisting cell death is a hallmark of all cancers. Furthermore, many cancer chemotherapeutic drugs cause the death of nerve cells and nerve fibers, therefore inducing neurological diseases in cancer patients. Using multiple state-of-the-art approaches, he aims to find the unknown components and molecular mechanisms of this type of cell death which will not only identify new drug targets for cancer treatments, but also shed light on how to reduce some side effects of chemotherapy.

Project title: "Biochemical and genetic dissection of axon degeneration"
Institution: Stanford University
Named Award: Layton Family Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Marc Tessier-Lavigne, PhD
Cancer Type: All Cancers
Research Area: Cell Death
Veronika Shoba, PhD

Dr. Shoba aims to develop a new class of small molecules that will target transcription factors, which regulate gene expression. These proteins are mutated in many cancers but are considered undruggable because current compounds fail to block the interaction between transcription factors and their binding partners. Dr. Shoba aims to disrupt these functional interactions by recruiting enzymes called kinases found in the human body to chemically modify the transcription factors and thus inhibit oncogenic activity. This strategy has the potential to diversify cancer-targeting approaches and become an essential tool in drug development.

Project title: "Phosphorylation-inducing chimeric small molecules"
Institution: The Broad Institute of MIT and Harvard
Award Program: Fellow
Sponsor(s) / Mentor(s): Amit Choudhary, PhD, and Stuart L. Schreiber, PhD
Cancer Type: All Cancers
Research Area: Chemical Biology
Sukrit Silas, PhD

Dr. Silas is investigating how naturally occurring microbial and viral proteins might be utilized in the fight against cancer. Complex interactions in bacterial communities (such as the gut microbiome) can often lead to genetic information being exchanged, modified, and reused by competing species. Dr. Silas will develop strategies to control the composition and behavior of these communities, potentially helping to mitigate the threat from antibiotic resistance and infectious disease, which can result in serious clinical complications in patients.

Project title: "Discovery and characterization of virally-encoded proteins of unknown function"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Joseph Bondy-Denomy, PhD, and Carol A. Gross, PhD
Cancer Type: All Cancers
Research Area: Basic Genetics
Digvijay Singh, PhD

Dr. Singh is using cryo-electron tomography for structural investigations of the phase-separated transcriptional sites inside the cells. Faulty regulation of transcription from DNA to RNA is one of the major hallmarks of cancer. Dr. Singh aims to gain knowledge about the transcriptional sites to explain how different components come together to carry out transcription, their relationships with the rest of the cell, and what can go wrong in the process to cause disease.

Project title: "Cryo-electron tomography of phase-separated transcription factories in situ"
Institution: University of California, San Diego
Award Program: Fellow
Sponsor(s) / Mentor(s): Elizabeth Villa, PhD
Cancer Type: All Cancers
Research Area: Cell Biology
Justin L. Sparks, PhD

Dr. Sparks is investigating the cellular machinery that carries out DNA replication and how this process can go awry in cancer cells. Specifically, he is focusing on the eukaryotic replisome, which is a complex of enzymes that helps cellular DNA replicate during cell division. He has found that the replisome can overcome bulky obstacles on a DNA strand, such as DNA-protein cross-links (DPCs), during replication to maintain genome integrity. DPCs, generated from cellular metabolites and environmental mutagens, are likely important for cancer etiology. Faulty DNA replication and repair are hallmarks of all cancers. Thus, his research has the potential to uncover new drug targets that can prevent genome instability and the evolution of cancers leading to therapeutic resistance.

Project title: "Replicative helicase bypass of bulky DNA lesions"
Institution: Harvard Medical School
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Biochemistry
Tyler Starr, PhD

Dr. Starr focuses on the process of how the immune system produces antibodies that specifically recognize and bind to antigens on pathogens and cancer cells. Dr. Starr is combining computational analyses of antibody sequences with experimental methods to test the effects of possible mutations on antibody function. This iterative process, similar to what the body does naturally, will help identify the best antibodies for an infection. The results of this research may lead to HIV therapeutics that reduce the incidence of AIDS-related cancers and improve the development of antibody-based cancer immunotherapies.

Project title: "The sequence-function landscape of antibody affinity maturation"
Institution: Fred Hutchinson Cancer Research Center
Award Program: Fellow
Sponsor(s) / Mentor(s): Jesse D. Bloom, PhD, and Frederick Matsen, PhD
Cancer Type: All Cancers
Research Area: Evolution
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