Other Cancers

Current Projects
Sylvan C. Baca, MD, PhD

Promising new treatments for cancers of the bladder and kidney have been developed, but, as with many cancer therapies, tumors eventually develop resistance. Research has shown that cancer cells resist treatment in part via epigenetic changes—those that do not affect the DNA sequence itself but turn important genes on or off, allowing cancers to survive under therapeutic stress. Dr. Baca is using novel techniques to study the epigenomes of cancer cells from blood samples. His goal is to understand how changes in the epigenomes of bladder and kidney cancers lead to treatment resistance. This knowledge will enable the design of better treatments and drug combinations that will benefit patients with metastatic bladder or kidney cancers.

Project title: "Epigenetic drivers of resistance to novel therapies for bladder and kidney cancer"
Institution: Dana-Farber Cancer Institute
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Toni K. Choueiri, MD
Cancer Type: Kidney and Bladder
Research Area: Epigenetics
Ben F. Brian, PhD

Abnormal interactions between our immune system and our gut microbes can lead to inflammation that drives colon and gastric cancer growth. Dr. Brian [HHMI Fellow] is investigating how the immune system recognizes and responds to these microbes, and how these interactions contribute to abnormal inflammation that can fuel cancer growth. Microbiota-immune interactions have been generally studied in the context of "clean" laboratory mice, but these models do not fully capture human immunology and the complex interplay between host cells and foreign microbes. To overcome this, Dr. Brian plans to study these interactions in "dirty" mice, colonized by a diverse community of microbes as well as pathogens. He will then use laboratory mice with more defined microbial communities to test how recognition of specific microbes by the immune system is regulated and how disruptions to this regulation contributes to inflammation. Dr. Brian received his PhD from the University of Minnesota, Twin Cities and his BS from the University of California, Santa Barbara.


Project title: "Mechanisms and consequences of microbiota-directed immune responses"
Institution: University of California, Berkeley
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Gregory M. Barton, PhD
Cancer Type: Gastric, Other Cancer, Colorectal
Research Area: Basic Immunology
Lauren E. Cote, PhD

Dr. Cote is exploring embryonic development to better understand how cells cooperate and build complex tissues. Since cancer cells often erroneously redeploy developmental programs and behaviors, her research into how neighboring cells align will yield insights into how cancerous cells metastasize and invade other tissues. Dr. Cote is combining tissue-specific genetic manipulations and laser cell ablations with live imaging during Caenorhabditis elegans digestive tract development to reveal how intracellular organization in one cell type can influence the alignment, polarity, and function of cells in the neighboring tissues.

Project title: "Constructing one continuous digestive tract, cell by cell"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Jessica L. Feldman, PhD
Cancer Type: Gastric, Other Cancer, Breast, Colorectal, All Cancers
Research Area: Developmental Biology
Allison L. Didychuk, PhD

Kaposi's sarcoma herpesvirus (KSHV) is a human oncogenic virus and the causative agent of cancers including Kaposi’s sarcoma, primary effusion lymphoma, and Multicentric Castleman disease. The related human herpesvirus Epstein-Barr Virus (EBV) is even more prevalent than KSHV, and is linked to cancers including Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. Dr. Didychuk [The Rhee Family Breakthrough Scientist] is investigating the mechanisms by which KSHV co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. A molecular understanding of how herpesviruses hijack the late gene transcription machinery will reveal new therapeutic weaknesses in the viral lifecycle and allow for structure-guided design of novel anti-viral drug targets.

Project title: “Understanding the mechanism of genome packaging in oncogenic herpesviruses"
Institution: Yale University
Named Award: The Rhee Family Breakthrough Scientist
Award Program: Dale Frey Scientist
Cancer Type: Blood, Other Cancer, Sarcoma
Research Area: Virology
Catherine A. Freije, PhD

Dr. Freije [Berger Foundation Fellow] is studying how the genetic diversity of hepatitis B virus (HBV) is shaped by its need to replicate and interact with specific host genes. Current antiviral therapeutics for HBV merely suppress infection and do not cure disease; as a result, patients with chronic HBV infection are at risk of developing liver cancer. Dr. Freije plans to uncover essential genomic regions that HBV needs to survive and persist, as well as those that counteract host genes that function to restrict these activities. This approach could provide insight into the progression of disease and has the potential to identify new antiviral therapeutics and ultimately reduce the incidence of HBV-associated liver cancer.

Project title: "Investigating the role of fitness and host pressure in shaping hepatitis B diversity"
Institution: The Rockefeller University
Named Award: Berger Foundation Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Charles M. Rice, PhD
Cancer Type: Other Cancer
Research Area: Virology
Jennifer M. Kalish, MD, PhD

Dr. Kalish is studying a rare hereditary syndrome called Beckwith-Wiedemann syndrome (BWS), which increases the risk of children developing kidney and liver cancers. These individuals have epigenetic changes on chromosome 11 that are found in other types of cancers. Epigenetic markers modify DNA so gene expression is turned on or off; changes in this process can cause cancer. By understanding how cancer is triggered in BWS, Dr. Kalish aims to identify pathways that can be targeted for the development of new treatments both for BWS patients and for others with cancers that have similar epigenetic changes. As a physician-scientist, Dr. Kalish established the BWS Registry, which compiles both clinical data and patient samples, and created the first human cell-based models of BWS.

Project title: "Epigenetic and genetic mechanisms of cancer in Beckwith-Wiedemann Syndrome"
Institution: Children's Hospital of Philadelphia
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Marisa S. Bartolomei, PhD, and Garrett M. Brodeur, MD
Cancer Type: Kidney and Bladder, Other Cancer, Pediatric
Research Area: Epigenetics
Nicholas P. Lesner, PhD

Ammonia, a waste product of cellular activity, is cleared from the body by the liver and kidneys through a process known as the urea cycle. During the urea cycle, ammonia is converted to urea, and arginine (an amino acid) is generated. When liver cells become cancerous, the urea cycle pathway stops functioning and cancer cells must import arginine from outside the cell. When cancer cells are prevented from importing arginine (via removal of arginine from the diet or genetic removal of the transporter), tumors do not grow, suggesting that arginine is critical for cells. However, the function of arginine in the cell is unclear. Using mass spectrometry and mathematical modeling, Dr. Lesner will identify the fate of arginine as it is metabolized by liver cancer cells in mouse models, and investigate how this is altered by various genetic mutations. Additionally, he will examine how restricting arginine from the diet genetically alters the liver and tumor cells. By understanding how disruption of this metabolic pathway influences liver cancer growth in the context of specific cancer drivers, Dr. Lesner aims to inform new therapeutic strategies. Dr. Lesner received his PhD from The University of Texas Southwestern Medical Center, Dallas and his BA from the University of Wooster, Wooster, Ohio.


Project title: "Hepatic urea cycle function in NASH-induced HCC progression"
Institution: University of Pennsylvania
Award Program: Fellow
Sponsor(s) / Mentor(s): M. Celeste Simon, PhD
Cancer Type: Other Cancer
Research Area: Metabolism
Aaron E. Lin, PhD

Dr. Lin [Walter Isaacson Fellow] is studying how hepatitis C virus (HCV) rewires cell biology and causes liver cancer. Modern HCV antiviral therapies are effective in curing hepatitis, but puzzlingly, recovered patients sometimes still develop cancer. This suggests that infection and subsequent inflammation permanently alter liver cells, but how this leads to cancer remains unclear. Dr. Lin is developing a CRISPR-based molecular "recorder" to determine whether cells that become more cancer-like have a history of infection and inflammation. This technology could identify genes that predispose healthy liver cells to infection, chronic immune stimulation, and transformation to cancer cells, which could point to potential therapeutic targets to interrupt the development of liver and other cancers.

Project title: "Contact tracing within an organism: developing a genome editing platform to record the history of virus-infected and transformed cells"
Institution: Princeton University
Named Award: Walter Isaacson Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Alexander Ploss, PhD, and Brittany Adamson, PhD
Cancer Type: Other Cancer
Research Area: Virology
Ysbrand Nusse, PhD

Dr. Nusse [Robert Black Fellow] studies how immune cells contribute to liver regeneration after injury. Injuries to mammalian tissues are typically repaired through a stepwise process of inflammation and debris clearance, followed by proliferation of progenitor cells and tissue reorganization. During chronic injury, this process can malfunction leading to excessive inflammation, uncontrolled tissue growth and cancer initiation. Dr. Nusse is investigating the role of eosinophils, a type of disease-fighting white blood cell, in liver damage and repair using mouse genetics and imaging within living tissues. This project aims to uncover how liver cancers arise from chronic liver damage and may also reveal insight into other forms of cancer.

Project title: "Defining the role of eosinophils in liver injury and repair"
Institution: University of Calgary
Named Award: Robert Black Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Paul Kubes, PhD
Cancer Type: Other Cancer
Research Area: Basic Immunology
David Y. Oh, MD, PhD

While immunotherapies such as anti-PD-1 therapy have provided an important treatment option for bladder cancer, the majority of patients do not respond to these regimens. This may reflect the distinct activation requirements of other immune T-cells besides CD8+ T-cells. In recent work, Dr. Oh and colleagues have identified cytotoxic (cancer cell-killing) CD4+ T-cells in human bladder cancer that are associated with immunotherapy responses. However, the regulation of cytotoxic CD4+ T-cells and how these mechanisms compare with CD8+ T-cells is not understood. Dr. Oh proposes to identify and validate surface receptors that enhance or inhibit the activity of cytotoxic CD4+ T cells in human bladder cancer, and the tumor antigens that are recognized specifically by these cells. He will also compare which of these regulatory mechanisms are unique to cytotoxic CD4+ T-cells relative to their CD8+ T-cell counterparts from the same patients. This work has the potential to increase both the proportion of bladder cancer patients who respond to immunotherapy as well as the quality of their response.

Project title: "Co-receptors modulating anti-tumor activity of human cytotoxic CD4+ effector cells"
Institution: University of California, San Francisco
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Lawrence Fong, MD
Cancer Type: Kidney and Bladder
Research Area: Immunotherapy
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