All Cancers

Current Projects
Brian H. Shirts, MD, PhD

Clinical testing for inherited cancer risk often leads to identification of rare genetic variants, but it is uncertain if these variants affect cancer risk. This uncertainty is difficult for cancer patients who want to know the best way to prevent future cancers in themselves and their families. 

Dr. Shirts is a clinical geneticist whose goal is to empower patients who have been diagnosed with rare genetic mutations (variants of uncertain significance, or VUS) to actively participate in family tree pedigree building to understand their own genetic risk for cancer and other diseases. He will develop an online toolkit to help cancer patients use publicly available genealogy and networking resources to determine if their own variants travel with cancer in their extended family. This project will pioneer an efficient way for patients and their families to work with genetics laboratories to classify VUS, giving cancer patients control over their own genetic information. This innovative strategy will also create a new source for the highest quality genotype-cancer correlation data, which will benefit cancer researchers and, eventually, everyone at risk for cancer.

 

Project title: "Participatory genetics for defining genotype-phenotype associations of rare cancer variants"
Institution: University of Washington
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Cancer Genetics
Michael J. Smanski, PhD

Dr. Smanski is examining magnetic nanoparticles (MNPs), which possess unique physical properties that have led to several clinical applications in cancer diagnosis and therapy. Several species of bacteria have been found to naturally produce MNPs with exquisite control over size and shape that is unmatched by current chemical synthesis methods. He aims to understand how bacterial synthesis of MNPs relies on the coordinated expression of several dozen genes.

Project title: "Establishing a versatile platform for functionalizing biological magnetic nanoparticles"
Institution: University of Minnesota
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Systems Biology
Ying Qi Shirleen Soh, PhD

Dr. Soh focuses on how viruses such as influenza evolve to infect diverse host species. Zoonotic transmissions of influenza from avian and swine hosts to humans have the potential to result in pandemics with severe public health consequences. Cancer patients, in particular, are disproportionately susceptible to complications arising from infection. Dissecting the pathways and mechanisms by which influenza can adapt to the human host will aid in the ability to predict and prevent pandemics resulting from zoonotic infection.

Project title: "Mapping paths and mechanisms of virus-host adaptation"
Institution: Fred Hutchinson Cancer Research Center
Award Program: Fellow
Sponsor(s) / Mentor(s): Jesse Bloom, PhD
Cancer Type: All Cancers
Research Area: Infectious Disease
Alexey A. Soshnev, MD, PhD

Dr. Soshnev [HHMI Fellow] studies how genetic information is packaged in the nucleus and how such packaging is interpreted by the cellular machinery. Changes in nuclear architecture may simultaneously affect the function of thousands of genes and are a hallmark of cancer. This research focuses on a family of small nuclear proteins termed "linker histones," which are thought to orchestrate higher-order folding of DNA in the nucleus. Understanding the molecular connection between the nuclear architecture and gene regulation will shed new light on the processes underlying oncogenic transformation.

Project title: "The study of linker histone H1 in transcriptional regulation and genome organization"
Institution: The Rockefeller University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): C. David Allis, PhD
Cancer Type: Blood, All Cancers
Research Area: Chromatin Biology
Justin L. Sparks, PhD

Dr. Sparks focuses on a protein complex called the eukaryotic replisome, which replicates cellular DNA during cell division. He is studying how the replisome handles persistent bulky DNA lesions that block the progression of the replicative helicase enzyme and how cells repair covalent DNA-protein cross-links (DPCs). DPCs are generated by formaldehyde and other endogenous metabolites and environmental mutagens and are almost certainly important for cancer etiology. Genome instability is a hallmark of all cancers, and mechanisms that either prevent or enhance this instability have many implications for cancer biology.

Project title: "Replicative helicase bypass of bulky DNA adducts?"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Johannes C. Walter, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
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: 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
Albert Tsai, PhD

Dr. Tsai is studying a process called translation, by which messenger RNAs (mRNAs) are decoded into proteins. A hallmark of cancer cells is distorted patterns of protein production, leading to uncontrolled growth and invasive behavior. He is using novel microscope technology to image live cells in real-time and developing techniques to image individual protein molecules during their synthesis, thereby linking the time, location and amount of protein production to individual mRNAs.

Project title: "Single-molecule imaging of transcription factors binding dynamics in Drosophila embryos"
Institution: HHMI Janelia Research Campus
Award Program: Fellow
Sponsor(s) / Mentor(s): Robert H. Singer, PhD
Cancer Type: All Cancers
Research Area: Biophysics
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