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
Srinjoy Chakraborti, PhD

Dr. Chakraborti is developing technologies to facilitate the rapid identification of individual, specific, safely targetable tumor antigens, and to engineer tumor chimeric antigen receptors (CARs) to specifically recognize and kill cancer cells within a clinically relevant timeline. Dr. Chakraborti also plans to use these technologies to investigate the role of helper T cells in enhancing the activity of anti-cancer killer T cells. These technologies, although applicable to adult cancers as well, will focus on antigens derived from pediatric cancer tissues because conventional therapies (such as chemotherapy and radiation) hold long-term health risks. 

Project title: Mining pHLA and T cell receptors (TCR) specificities by phage display for de novo TCR engineering and personalized cancer therapy
Institution: Albert Einstein College of Medicine
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Jonathan R. Lai, PhD
Cancer Type: Other Cancer, Pediatric
Research Area: Immunotherapy
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
Award Program: Fellow
Sponsor(s) / Mentor(s): Britt Glaunsinger, PhD
Cancer Type: Other Cancer, Sarcoma
Research Area: Virology
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
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: "Elucidating the connection between clonal hematopoiesis and lymphoma in humans"
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
Christopher A. Klebanoff, MD

A form of cancer immunotherapy termed adoptive T cell transfer (ACT) can induce long-lasting remissions in patients with advanced blood cancers. In this approach, T white blood cells specific for proteins found on the surface of cancer cells (antigens) are activated and expanded outside the immunosuppressive environment of a cancer patient's body before re-infusion as a therapy. Thus far, this promising form of cancer immunotherapy has failed to work in most patients with cancers arising from solid organs, the leading cause of cancer-related deaths in adults. Two critical gaps in knowledge limit the ability of ACT to be successfully applied to solid cancers: 1) understanding which antigens on the surface of cancer cells can be targeted by T cells that do not have the potential to cross-react and injure normal tissues, and 2) insight into what factor(s) limit the ability of transferred T cells to expand and persist following re-infusion into a patient. Dr. Klebanoff seeks to use a genetic engineering approach to simultaneously address both these issues. Success of these efforts would be a decisive step forward toward extending the ability of ACT to deliver potentially curative responses in patients with common cancers, including those arising from the breast, uterus, cervix and colon.

Project title: "Clinical development of next-generation T cell receptor (TCR)-based adoptive immunotherapies for the treatment of patients with common epithelial malignancies"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Michel Sadelain, MD, PhD, and Larry Norton, MD
Cancer Type: Gynecological, Kidney and Bladder, Breast
Research Area: Immunotherapy
Nora Kory, PhD

Dr. Kory focuses on cancer cell metabolism. Cancer cells are characterized by rapid and uncontrolled cell growth. To sustain their accelerated growth, cancer cells rely on a constant supply of building blocks produced by specific metabolic pathways. One metabolic pathway, the mitochondrial one-carbon pathway, has recently been found to be especially important for the growth and survival of tumors and correlates with the survival of cancer patients. Inhibiting this pathway is a promising new strategy to treat cancer; however, its key components are still unknown. She aims to identify these components using a genetic screen applying the gene-editing CRISPR-Cas9 system to identify all genes required for its function in human cancer cells. She hopes to elucidate how cancer cells alter their metabolism to meet their high demands for building blocks and energy, which may also lead to the development of new drugs to treat cancers.

Project title: "Identifying new components of mitochondrial one-carbon metabolism"
Institution: Whitehead Institute for Biomedical Research
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David M. Sabatini, MD, PhD
Cancer Type: Other Cancer
Research Area: Biochemistry
Amaia Lujambio, PhD

Immunotherapy is revolutionizing the clinical management of a variety of cancers. Unprecedented complete responses have been observed in hepatocellular carcinoma (HCC), a type of liver cancer that shows little response to conventional therapeutic approaches. Unfortunately, the clinical efficacy of nivolumab (Opdivo), a novel immune checkpoint inhibitor, is limited to less than 20% of HCC patients. Understanding the determinants of sensitivity and resistance to nivolumab and developing strategies that overcome resistance are therefore urgently needed to significantly improve the clinical management of HCC patients. Dr. Lujambio will combine the use of a novel mouse model of liver cancer and samples from HCC patients treated with nivolumab to identify genes that are involved in intrinsic and acquired resistance to this therapy. These findings will be critical to define biomarkers to select the HCC patients that are most likely to benefit from this immunotherapy. Moreover, a better understanding of the mechanisms of resistance to nivolumab will help design strategies to overcome resistance, providing novel therapeutic options for resistant patients.

Project title: "Overcoming the resistantce to anti-PD1 immunotherapy in hepatocellular carcinoma"
Institution: Icahn School of Medicine at Mount Sinai
Award Program: Innovator
Cancer Type: Other Cancer
Research Area: Immunotherapy
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