All Cancers

Current Projects
Benjamin M. Stinson, PhD

Our DNA is constantly subjected to damage, and our cells must repair this damage to ensure survival. Breaks in DNA that completely sever DNA molecules are particularly toxic, and failure to repair these breaks can lead to genetic alterations that drive cancer initiation and progression. Dr. Stinson studies the two main cellular pathways that repair these DNA breaks: non-homologous end joining (NHEJ) and homologous recombination (HR). Defects in these pathways are linked to predisposition to many cancers, including leukemia, breast, ovarian, and prostate cancers. His prior work has demonstrated how NHEJ minimizes genetic alterations during DNA break repair. Ongoing work will elucidate fundamental mechanisms of HR that suppress cancer and seek to identify new HR factors. This work has important clinical implications for identifying patients that may benefit from treatments that target HR-defective tumors and for discovering potential mechanisms of resistance to treatment.

Project title: "Mechanism of DNA processing during non-homologous end joining"
Institution: Dana-Farber Cancer Institute
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Biochemistry
Mark R. Sullivan, PhD

Many types of cancer, chemotherapy, and numerous other underlying conditions can leave patients vulnerable to infection by bacteria that would normally be unable to survive in the body. These opportunistic infections are challenging to treat, as antibiotics are often ineffective against these pathogens or have serious side effects not well-tolerated by individuals with underlying conditions. Dr. Sullivan studies how opportunistic infections occur, with a particular focus on lung infection. His ongoing work is centered on identifying bacterial adaptations that enable pathogens to survive both the host defense systems present in the lung as well as antibiotic treatment. His work will help deepen our understanding of opportunistic infection and may provide novel avenues for more effective and tolerable treatment of these pathogens.

Project title: “Identifying determinants of pathogenesis and drug resistance in opportunistic lung infection”
Institution: Harvard T.H. Chan School of Public Health
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Infectious Disease
Mark R. Sullivan, PhD

Dr. Sullivan [Merck Fellow] studies the processes that lead to opportunistic infections affecting cancer patients. The human body, which is a hostile environment for pathogens, is well-equipped to fend off infections from most bacteria. However, cancer and chemotherapy can cause inflammation, tissue damage, and impairment of the immune system in ways that leave patients vulnerable to bacterial infection. These opportunistic infections are challenging to treat, as antibiotics often have little effect on these bacteria. Dr. Sullivan aims to identify the bacterial components that allow opportunistic pathogens to live within the lung and survive antibiotic treatment. This research will be critical to discovering more effective therapies to eradicate these infections.

Project title: "Identifying requirements for lung infection by opportunistic pathogens"
Institution: Harvard T.H. Chan School of Public Health
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Eric J. Rubin, MD, PhD
Cancer Type: All Cancers
Research Area: Infectious Disease
James C. Taggart, PhD

Antimicrobial resistance is a growing crisis that imperils our ability to protect patients immunocompromised by cancer treatment. Despite this, the few new antibiotics currently in clinical trials primarily use established mechanisms of action. Identification of new targets for antimicrobial drugs is thus an urgent clinical need. Recent work has shown that bacteria can tolerate substantial inhibition of many proteins thought to be essential for growth, rendering them poor drug targets. The mechanisms that cause this robustness are poorly understood. By combining cutting-edge microfluidic technologies with methods for controlled gene repression, Dr. Taggart will systematically identify mechanisms that allow bacterial cells to tolerate inhibition of genes critical for cellular growth. This work will guide the selection of targets for future antibiotic development and may reveal mechanisms by which to sensitize bacterial cells to existing drugs. Dr. Taggart received his PhD from Massachusetts Institute of Technology, Cambridge and his BS from Haverford College, Haverford.

Project title: "Mechanistic interrogation of robustness and vulnerability in a bacterial essential gene network"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Allon M. Klein, PhD, and Johan Paulsson, PhD
Cancer Type: All Cancers
Research Area: Systems Biology
Jung-Shen Benny Tai, PhD

Dr. Tai studies bacterial biofilms or aggregates of bacterial cells in an extracellular matrix. Biofilms play a critical role in many health and industry settings. Biofilm-forming bacteria and imbalance in patients’ gut microbiota have been found to correlate with cancer development, and cancer patients receiving therapy frequently suffer from bacterial infections. From the unique perspectives of microbiology, soft matter physics, and ecology, Dr. Tai aims to decipher how, at the single bacteria cell level, heterogeneities in cell shape, organization, and gene expression constitute the function and development of their collective communities: biofilms. His work is expected to deepen our understanding of bacterial biofilms and ultimately contribute to therapeutic strategies.

Project title: "From form to function: Cell shape, cell ordering, and gene regulation in bacterial biofilm"
Institution: Yale University / Michigan State University
Award Program: Fellow
Sponsor(s) / Mentor(s): Jing Yan, PhD (Yale University), and Christopher Waters, PhD (Michigan State University)
Cancer Type: All Cancers
Research Area: Microbiology
Akanksha Thawani, PhD

Dr. Thawani [Merck Fellow] studies selfish DNA sequences—so called because they copy and paste themselves within the human genome despite offering no specific fitness advantage. Dr. Thawani will utilize advanced methods such as cryo-electron microscopy to reveal the cellular machinery that assists these selfish elements and thus delineate their mechanism of mobility. She will use this insight to engineer new genome editing technologies to precisely insert large genes at user-specified sites in a variety of human cell types. This general technology will not only translate directly into new gene therapies, but also result in wide-ranging applications in synthetic biology. Ultimately, this work will contribute to treatment for many cancer types, including improved CAR-T therapies for blood cancers.

Project title: "Targeted genetic supplementation by harnessing transposable elements"
Institution: University of California, Berkeley
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Eva Nogales, PhD, and Kathleen Collins, PhD
Cancer Type: All Cancers
Research Area: RNA (RNA processing, miRNA and piRNA mechanisms, enzymatic RNAs, etc.)
Erron W. Titus, MD, PhD

Chimeric antigen receptor (CAR) T cells are immune cells that have been genetically engineered to bind specific proteins on cancer cells. CARs can display exquisite sensitivity and discrimination, and CAR T cells have been deployed with spectacular success to detect and kill blood cancers. Unfortunately, they are much less effective against “solid” tumors, such as breast or kidney cancers. To address this problem, Dr. Titus [Connie and Bob Lurie Fellow] is designing T cells with membrane proteins that perform novel functions, including proteins that facilitate membrane fusion or alter the adhesion between T cells and their targets. By redesigning T cell membranes, Dr. Titus hopes to create useful cancer-fighting tools that can be deployed in conjunction with other emerging cellular therapies and immunotherapies. Dr. Titus received his MD and PhD from the University of California, San Francisco, and his AB from Harvard University.

Project title: "Engineered cellular fusogens for novel immune effector functions"
Institution: University of California, San Francisco
Named Award: Connie and Bob Lurie Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Matthew F. Krummel, PhD
Cancer Type: All Cancers
Research Area: Immunotherapy
Catherine Triandafillou, PhD

One of the tools cancer cells employ to evade immune system detection is an increased DNA mutation rate, with some cancers mutating 100-1000 times faster than healthy tissue. Classic studies of the effects of mutations predict that most genetic changes are deleterious, yet high mutation rates appear to help cancer cells adapt and invade. Dr. Triandafillou [National Mah Jongg League Fellow] will address this paradox by using a single-cell model of cancer to measure the effects of mutations with much greater accuracy and resolution than is possible in live cancer cells. This information will help us understand how cancer cells balance deleterious mutations with the ability to adapt, and how the effects of mutations interact. She will also perform laboratory evolution experiments to track the adaptive process in different environmental conditions, mimicking the process by which cancer cells are able to colonize new micro-environments within tumors and throughout the body. This work will provide a clearer picture of how cancer cells use new mutations to proliferate. Dr. Triandafillou received her PhD from the University of Chicago and her BS from Temple University.

Project title: "Intrinsic and extrinsic drivers of heterogeneous drug resistance in cancer"
Institution: University of Pennsylvania
Named Award: National Mah Jongg League Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Arjun Raj, PhD
Cancer Type: Colorectal, Skin, All Cancers
Research Area: Evolution
Srinivas R. Viswanathan, MD, PhD

Epidemiologic studies have revealed that many cancer types display differences in incidence or outcomes between the sexes. In most cases, these differences are only partially explained by non-genetic factors such as hormonal differences, carcinogen exposure, lifestyle, and access to health care. Our understanding of how genetic factors contribute to differences in cancer incidence between the sexes remains incomplete. A fundamental genetic difference between the sexes is in chromosome composition. Relative to male somatic cells, female somatic cells have an extra X chromosome. Most genes on the second copy of chromosome X in females are inactivated via a process known as X-chromosome inactivation, which approximately equalizes the dosage of X-linked genes between males and females. Dr. Viswanathan's project tests the hypothesis that genetic alterations to the X chromosome in cancer may perturb this carefully regulated process and thereby contribute to differences in cancer incidence or pathogenic mechanisms between males and females.

Project title: "X marks the spot: exploring how X-chromosome alterations drive sex differences in cancer"
Institution: Dana-Farber Cancer Institute
Award Program: Innovator
Cancer Type: Kidney and Bladder, All Cancers
Research Area: Cancer Genetics
Lexy von Diezmann, PhD

Dr. von Diezmann is a biophysicist who studies how cells regulate the pathway used to repair broken DNA. Errors in specific DNA repair pathways are an early step in the development of many cancers, such as with defects in homologous recombination for breast, ovarian, and pancreatic cancers. The Diezmann lab uses high-resolution microscopy techniques to visualize the process by which DNA breaks are designated for specific repair fates, working primarily in live meiotic nuclei of the model organism C. elegans. By elucidating the mechanisms by which protein assemblies form and transmit information along chromosomes and throughout the nucleus, her lab will help provide a foundation for the development of novel chemotherapies based on modulating the DNA damage response.

Project title: "Single-molecule dynamics of DNA repair assemblies in live cells"
Institution: University of Minnesota
Award Program: Dale Frey Scientist
Cancer Type: Pancreatic, All Cancers
Research Area: Chromosome and Telomere Biology
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