Other Cancers

Current Projects
Vivek K. Arora, MD, PhD

Modern molecular characterization of tumors of the urinary bladder has illuminated cellular pathways that may be important for bladder cancer development. Dr. Arora is investigating the role played by a family of proteins called nuclear receptors in driving bladder cancer development and progression. These studies will provide insights into the fundamental basis of bladder cancer, while validating potential drug targets. Nuclear receptors are particularly attractive drug targets because they are highly amenable to modulation with drugs. He hopes to pave the way for the development of drugs to effectively target nuclear receptors in bladder cancer.

Project title: "Defining a targetable oncogenic dyad in bladder cancer"
Institution: Washington University
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Lee Ratner, MD, PhD
Cancer Type: Kidney and Bladder
Research Area: Cancer Genetics
Brian C. Capell, MD, PhD

Squamous cell carcinoma (SCC) can occur on a number of epithelial surface tissues ranging from the skin and lung to the esophagus and oropharynx, and collectively, are the most common form of cancer in the world. Recent sequencing studies have found that mutations in epigenetic regulators that control gene expression frequently occur in all forms of SCC. Dr. Capell aims to harness the great accessibility of human skin to understand how altered epigenetics promotes cutaneous SCC. Given that epigenetic changes are inherently reversible and numerous epigenetic drugs are currently in development, he hopes that by understanding these mechanisms he will identify better therapies for these incredibly common and potentially deadly cancers.

Project title: "Defining the role of epigenetic enhancer dysfunction in epithelial carcinogenesis"
Institution: University of Pennsylvania, Philadelphia
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Shelley L. Berger, PhD
Cancer Type: Other Cancer
Research Area: Epigenetics
Allison Didychuk, PhD

Dr. Didychuk is investigating the mechanism by which the Kaposi’s sarcoma herpesvirus (KSHV) co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. This research should reveal insights into this unique mode of transcriptional control. KHSV is an oncogenic virus that causes various cancers including, Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease, in immunocompromised individuals.

Project title: "Viral mimics of host transcription factors in oncogenic herpesviruses"
Institution: University of California, Berkeley
Named Award: The Rhee Family Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Britt Glaunsinger, PhD
Cancer Type: Blood, Other Cancer, Sarcoma
Research Area: Virology
Gregory S. Ducker, PhD

One of the unique features of liver cancer is the way in which it obtains and uses different forms of energy, especially fats. Drs. Evason and Ducker found that a certain type of fat (phosphatidylcholine lipids) is elevated in both zebrafish and human liver cancer cells. They are using zebrafish, which form tumors similar to the human disease and can be easily manipulated to study liver cancer. The goal of this project is to determine why phosphatidylcholine lipid levels are higher in liver cancer and how they might be targeted with drugs to prevent or cure this disease.

Project title: "Targeting phosphatidylcholine metabolism in liver cancer using zebrafish"
Institution: Huntsman Cancer Institute at the University of Utah
Award Program: Innovator
Cancer Type: Other Cancer
Research Area: Animal Models/Mouse Models
Jonathan C. Dudley, MD

Earlier cancer detection usually means a greater chance of remission or cure, but cost-effective and highly specific cancer screening is not yet available for most cancers. More than 90 percent of cancers harbor aneuploidy, an abnormal number of chromosomes in a cell; this abnormality is highly specific for cancer and can be detected with DNA sequencing. Dr. Dudley is developing a new approach for detecting cells with abnormal amounts of DNA, which could identify cancer sooner. He aims to apply this approach to urine and Pap smear samples to create an inexpensive and sensitive screening test for bladder, ovarian and endometrial cancers.

Project title: "Earlier detection of cancer in body cavity fluids through aneuploidy analysis after cell enrichment and partitioning"
Institution: The Johns Hopkins University School of Medicine
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Bert Vogelstein, MD
Cancer Type: Gynecological, Kidney and Bladder
Research Area: Diagnostics
Adam D. Durbin, MD, PhD

Dr. Durbin is developing new ways to target neuroblastoma, using chemical inhibitors and genetic techniques to disrupt small RNA species and enzymes that neuroblastoma cells require for survival. These new factors will also be inhibited in animal models of human neuroblastoma, alone and in combination with drugs similar to those entering clinical trials. These studies aim to identify new levels of gene regulation and methods to inhibit the genes involved in formation of neuroblastoma, with minimal side effects.

Project title: "Interrogation of neuroblastoma dependencies and non-coding RNAs on the core-regulatory circuitry for therapeutic inhibition"
Institution: Dana-Farber Cancer Institute
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): A. Thomas Look, MD
Cancer Type: Other Cancer, Pediatric
Research Area: Epigenetics
Kimberley J. Evason, MD, PhD

One of the unique features of liver cancer is the way in which it obtains and uses different forms of energy, especially fats. Drs. Evason and Ducker found that a certain type of fat (phosphatidylcholine lipids) is elevated in both zebrafish and human liver cancer cells. They are using zebrafish, which form tumors similar to the human disease and can be easily manipulated to study liver cancer. The goal of this project is to determine why phosphatidylcholine lipid levels are higher in liver cancer and how they might be targeted with drugs to prevent or cure this disease.

Project title: "Targeting phosphatidylcholine metabolism in liver cancer using zebrafish"
Institution: Huntsman Cancer Institute at the University of Utah
Award Program: Innovator
Cancer Type: Other Cancer
Research Area: Animal Models/Mouse Models
Ryan A. Flynn, MD, PhD

Dr. Flynn aims to understand the interplay between cancer metabolism and RNA biology at the level of protein modifications, such as glycosylation. The use of metabolites to fuel cellular processes including cell division and protein synthesis are critical in both healthy tissue and cancer growth. This work will define glycosylation events that respond to and regulate the cancer state within RNA-based networks, thereby establishing new layers of regulation for future therapeutic targeting.

Project title: "The interplay between cellular metabolism and RNA homeostasis in disease"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Carolyn R. Bertozzi, PhD
Cancer Type: Other Cancer
Research Area: Chemical Biology
Christopher J. Gibson, MD

Christopher’s research centers on the earliest steps whereby normal cells transform into abnormal cells with the potential to become cancer. He will focus on better understanding the first steps of the process by which normal blood cells become lymphomas, cancers that are generally thought to arise from blood cells that have already committed to becoming lymphocytes, an important component of the immune system. He hypothesizes, however, that some lymphomas actually arise from earlier hematopoietic stem cells (HSCs). He will interrogate this hypothesis by studying a cohort of lymphoma patients who also have detectable genetic mutations in HSCs that are known to be associated with blood cancers – a condition known as clonal hematopoiesis of indeterminate potential, or CHIP – to determine whether the mutations in the HSCs were the earliest events in the development of the patients’ lymphomas. Having a better understanding of lymphomas’ cellular basis will hopefully allow new insights into their clinical behavior and therapeutic vulnerabilities.

Project title: "The biology and clinical implications of clonal hematopoiesis in cancer patients"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Benjamin L. Ebert, MD, PhD
Cancer Type: Blood, Other Cancer
Research Area: Cancer Genetics
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. Dr. Kalish works under the mentorship of Marisa Bartolomei, PhD, at Children’s Hospital of Philadelphia, Philadelphia.

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 A. Brodeur, MD
Cancer Type: Other Cancer
Research Area: Epigenetics
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