All Cancers

Current Projects
Fangyu Liu, PhD

Dr. Liu’s research focuses on discovering new drug candidates to treat pancreatic, colorectal, breast, and prostate cancers. Using advanced computational techniques to screen billions of chemical compounds, she aims to identify and develop highly specific molecules that target critical pathways in cancer cells while sparing healthy tissues. For example, she has uncovered compounds that modulate calcium-sensing receptors, which play a role in certain cancers, with reduced side effects compared to the current standard-of-care. She is now applying these insights to improve treatments that boost immune responses against tumors. Dr. Liu’s work not only strives to create new cancer therapies but also deepen our understanding of the complex interactions within tumors, paving the way for precision medicine tailored to individual patients.

 
Project title: "Targeting membrane enzymes for next-generation precision medicine against cancer"
Institution: University of Texas Southwestern Medical Center
Award Program: Dale Frey Scientist
Cancer Type: Pancreatic, All Cancers
Research Area: Chemical Biology
Jingchuan Luo, PhD

Metastatic cancers exploit cellular machinery to increase their proliferative potential and direct invasive cell migration. Specifically, cancer cells can adjust the translation of RNA into proteins to keep up with the demands of growth and metastasis. An important way that cells fine-tune their translation and quickly modulate cellular responses is through localized translation, or the translation of proteins in other areas of the cell further from the nucleus. To study the scope of localized translation, Dr. Luo has developed a highly sensitive, spatially-specific, and optically-controlled technique, which enables the quantification of translation at any given subcellular location. She will focus on understanding mechanisms of localized translation by identifying which genes are locally translated, how they are regulated, and why this process is important. Understanding the molecular mechanism of local protein synthesis could yield invaluable insights into the basis of cancer metastasis and inform therapeutic strategies. 

Project title: “Decoding the role of localized translation in normal physiology and cancer metastasis”
Institution: Whitehead Institute for Biomedical Research
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Cell Biology
J. Scott P. McCain, PhD

One of the defining features of cancerous cells is that they divide quickly. The composition of the human microbiome is also due to differences in how quickly microbes grow. How do we determine how fast cells are growing in their natural environment? Is there a way to take a ‘snapshot’ and turn it into a ‘growth rate’? This is the fundamental problem Dr. McCain is studying. He is using computational simulations, machine learning, and experiments with bacteria to determine the optimal way to use markers of gene expression to estimate these critical rates. This project will provide fundamental insights into the use of gene expression data to key processes like growth rate or metabolite secretion rate, both of which have implications for cancer biology. Dr. McCain received his MSc and PhD from Dalhousie University and his BSc from the University of Western Ontario.

Project title: "Estimating growth rates and fluxes using gene expression: Theory and applications"
Institution: Massachusetts Institute of Technology
Award Program: Fellow
Sponsor(s) / Mentor(s): Gene-Wei Li, PhD
Cancer Type: All Cancers
Research Area: Microbiology
Rebecca S. Moore, PhD

Sleep problems may be a risk factor for developing certain types of cancer—lung, colon, pancreas, and breast—and may affect the progression of these cancers and the effectiveness of their treatment. Conversely, symptoms of cancer or side effects of treatment, including restless legs and obstructive sleep apnea, may cause sleeping problems, reducing quality of life. Understanding the complex relationship between cancer and sleep creates opportunities to improve health, treatment options, and quality of life. Specifically, understanding how the peripheral nervous system and the brain regulate both the timing and rhythmicity of sleep (i.e., circadian control), and the balance between time awake and growing sleep pressure (i.e., homeostatic control), could improve survival rates and the quality of cancer treatment. To this end, Dr. Moore [HHMI Fellow] aims to identify the role of circulating dietary cholesterol on sleep and to conduct a targeted genetic screen to identify peripherally secreted proteins that affect either the circadian or the homeostatic control of sleep. These results will provide a means for therapeutic interventions to ameliorate the effects of sleep disruption. Dr. Moore received her PhD from Princeton University and her MS and BS from the City College of New York.

Project title: "Investigation of the role of peripheral secreted molecules on sleep and circadian rhythms"
Institution: University of Pennsylvania
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Amita Sehgal, PhD
Cancer Type: All Cancers
Research Area: Basic Genetics
Meghan A. Morrissey, PhD

Certain immunotherapies work by instructing macrophages, a type of innate immune cell, to attack the tumor by phagocytosing, or eating cancer cells. However, macrophages rarely eat an entire cancer cell within a solid tumor. Instead, they nibble pieces off the cancer cell, a process called trogocytosis. While phagocytosis kills the cancer cell, trogocytosis usually doesn’t – and worse, nibbling removes the markers on the cancer cell that allow the immune system to recognize it as a threat. Dr. Morrissey is studying why some cancer cells die after being nibbled while others survive, with the goal of making macrophage-activating immunotherapies more effective. Specifically, she is studying Her2-positive breast and ovarian cancers, as it has been shown that Her2 immunotherapies cause trogocytosis instead of phagocytosis. This research could enhance any immunotherapy that is designed to activate macrophage phagocytosis, improving treatment of diverse cancers like lung cancer, lymphoma, and glioblastoma.

Project title: "Nibbled to death: improving macrophage's ability to kill solid tumors by trogocytosis"
Institution: University of California Santa Barbara
Named Award: Nadia's Gift Foundation Innovator
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Cell Biology
Ryan Y. Muller, PhD

The PABPC1 protein has diverse roles in gene expression control that span functions in mRNA stability, polyA tail length control, and translation regulation. PABPC1 gene amplifications are detected in roughly 4% of cancer samples, but it is unclear how PABPC1 fits into the picture of cancer progression. Dr. Muller [HHMI Fellow] studies the sequence preferences of PABPC1 protein to understand the mechanistic details that determine which transcripts are subject to PABPC1-mediated regulation. Connecting these sequence preferences to the mis-regulation caused by excess PABPC1 may provide a therapeutic handle for cancers that contain PABPC1 gene amplifications. Dr. Muller received his PhD from the University of California, Berkeley and his BS from Arizona State University, Tempe.

Project title: “The molecular determinants of PABP-mediated gene regulation”
Institution: Whitehead Institute for Biomedical Research
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David P. Bartel, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Christopher Noetzel, PhD

As different tissues in the body form, cells need to undergo a complex, precisely timed series of differentiation programs to form specialized cell types. Importantly, premature or delayed initiation of these programs can contribute to cancer formation. However, how timing of cellular differentiation is encoded on a molecular level is poorly understood. Dr. Noetzel is using the protozoan parasite Cryptosporidium parvum as a simplified model of eukaryotic differentiation. After infecting the intestinal lining of a mammalian host, these single-celled parasites undergo exactly three rounds of asexual replication before collectively differentiating into gametes. These studies will investigate how this hard-wired, intrinsic developmental timer is encoded. In his project, Dr. Noetzel aims to understand how these parasites "count to three," which will inform our basic understanding of how eukaryotic cells keep track of time during development. Dr. Noetzel received his PhD from the Weill Cornell Medical College, Cornell University, New York and his MSc and BSc from Georg-August-University, Göttingen.

 

Project title: "How do eukaryotic cells count cell cycles? Intrinsic regulation of quantized asexual replication cycles and commitment to sexual differentiation in the protozoan parasite Cryptosporidium parvum"
Institution: University of Pennsylvania
Award Program: Fellow
Sponsor(s) / Mentor(s): Boris Striepen, PhD
Cancer Type: All Cancers
Research Area: Microbiology
Expery O. Omollo, PhD

Dr. Omollo [Robert A. Swanson Family Fellow] studies how bacteria have evolved to achieve precise gene expression using strategically placed transcription terminators. In cancer cells, specific mutations lead to uncontrolled transcription of certain genes, resulting in elevated gene expression that fuels cancer progression. Using bacteria as a model, Dr. Omollo aims to uncover how RNA polymerases in cancer cells evade termination signals to maintain high levels of gene expression, encouraging cancer spread. Dr. Omollo received his PhD from University of Wisconsin-Madison, Madison and his BS from Michigan State University, Lansing.

Project title: "Elucidating what determines the strength of bacterial transcription terminators"
Institution: Massachusetts Institute of Technology
Named Award: Robert A. Swanson Family Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Gene-Wei Li, PhD
Cancer Type: All Cancers
Research Area: Computational Biology
Jeremy A. Owen, PhD

Chromatin remodelers are complex protein machines responsible for packaging DNA and regulating gene expression. Their dysfunction is strongly implicated in cancer. For example, certain types of sarcoma and ovarian cancer are driven by mutations in a chromatin remodeler called BAF. Combining experiments with theoretical work, Dr. Owen’s research aims to understand how remodelers recognize their target sites in the cell’s nucleus. By expanding our understanding of chromatin remodeling, the findings of this research will provide the groundwork for more effective cancer treatments—suggesting how drugs might target chromatin remodelers—as well as enhance our understanding of how existing drugs that target remodeler-adjacent mechanisms might work.

A central aim of this project is the development of new, quantitative models to explain the behavior of chromatin remodelers seen in experiments. Dr. Owen will achieve this by successive rounds of passing between theory and experiments repeatedly—measuring, modeling, then measuring again. For comparison to experiments, model predictions will be extracted computationally (e.g., numerically solving ODEs, or by exact stochastic simulation using Gillespie’s algorithm) or analytically (e.g., by the King-Altman procedure, and variants), as appropriate.

Project title: "The biophysics of substrate recognition in chromatin remodeling"
Institution: Princeton University
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Tom W. Muir, PhD, and Ned S. Wingreen, PhD
Cancer Type: Gynecological, Sarcoma, All Cancers
Research Area: Chromatin Biology
Sangwoo Park, PhD

One way cancer cells evade immune attack is by constructing a thin material barrier called the glycocalyx on their surface to evade detection and destruction by surveilling immune cells. Tiny changes in the glycocalyx thickness, as small as 10 nanometers, can affect the anti-tumor activity of immune cells, including CAR T cells. Dr. Park’s [Merck Fellow] goal is to develop strategies to endow CAR T cells with the ability to penetrate the glycocalyx barrier in solid tumors such as breast cancer and glioblastoma. These strategies will increase the effectiveness of CAR-T cell therapy against solid tumors by overcoming a significant mechanism of immune cell evasion. Dr. Park received his PhD from Cornell University, Ithaca and his BS from Korea Advanced Institute of Science and Technology, Daejeon.

Project title: "Engineering novel CAR T cells targeting cancer glycocalyx barrier"
Institution: Massachusetts General Hospital
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Marcela V. Maus, MD, PhD
Cancer Type: Brain, Breast, All Cancers
Research Area: Tumor Immunology
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