Other Cancers

Current Projects
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
Amaia Lujambio, PhD

Immunotherapy is revolutionizing the clinical management of a variety of cancers, including hepatocellular carcinoma (HCC), a type of liver cancer that shows little response to conventional therapeutic approaches. Recently, two immune checkpoint inhibitors, nivolumab (Opdivo) and pembrolizumab (Keytruda), have been approved as second line therapy after showing unprecedented complete responses in clinical trials. However, not all patients are sensitive to these anti-PD1 drugs, highlighting the urgent need to identify biomarkers for optimal patient selection and strategies to overcome resistance. Dr. Lujambio is using a novel mouse model of liver cancer and samples from HCC patients treated with checkpoint inhibitors to identify genes that are involved in intrinsic and acquired resistance to this therapy. These findings will be critical to define biomarkers that identify HCC patients who are most likely to benefit from this immunotherapy. Moreover, her findings may lead to the design of combination therapies that effectively treat more patients.

Project title: "Overcoming resistance 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
Vitor Mori, PhD

New technologies developed in the last decade have enabled chemotherapy to be delivered directly to lung tumors intratumorally in contrast to systemic delivery that affects the whole body. Recent studies have shown a partial or complete response ratio of 71% with significantly fewer side effects for patients treated intratumorally with cisplatin. Dr. Mori is modeling cisplatin pharmacodynamics following injections, taking into consideration the heterogeneity of the tumor microenvironment. This research aims to optimize drug delivery strategy to enhance targeting tumor cells while reducing side effects. 

 

Project title: "EBUS-TBNI of cisplatin optimization in heterogeneous lung tumors"
Institution: University of Vermont
Award Program: Quantitative Biology Fellow
Sponsor(s) / Mentor(s): Jason H.T. Bates, PhD, DSc, and C. Matthew Kinsey, MD
Cancer Type: Kidney and Bladder, Lung
Nagarajan Nandagopal, PhD

Dr. Nandagopal is focusing on genes in the bHLH family and their role in signal integration to help decide whether cells grow and divide, differentiate, migrate, or even die. bHLH genes are involved in fate choices in stem cells of the brain, intestines, skin, and other tissues. They are also commonly misregulated in cancers, such as neuroblastomas and glioblastomas. By comparing signal integration by bHLH circuits in normal and cancer cells, Dr. Nandagopal aims to discover how errors in fate decisions occur, and how they can be corrected. 

Project title: "Signal integration by bHLH circuits to enable cell fate decisions"
Institution: Harvard Medical School
Named Award: Philip O’Bryan Montgomery Jr. MD Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Galit Lahav, PhD, and Sean Megason, PhD
Cancer Type: Other Cancer
Research Area: Systems Biology
Alexandra Nguyen, PhD

Dr. Nguyen aims to identify the molecular differences between cancer cells and healthy cells, using large-scale genetic approaches in acute myeloid leukemias. Cancer cells exhibit a high degree of diversity in the cellular pathways utilized for survival. Identifying these cellular differences could provide a method to strategically target and kill cancerous cells while minimizing the off-target effects to healthy cells.

Project title: "Defining the cell type specific cell division requirements in acute myeloid leukemias"
Institution: Whitehead Institute for Biomedical Research
Award Program: Fellow
Sponsor(s) / Mentor(s): Iain M. Cheeseman, PhD
Cancer Type: Blood, Other Cancer
Research Area: Cancer Genetics
Ysbrand Nusse, PhD

Dr. Nusse 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
Juhee Pae, PhD

Dr. Pae is investigating the regulation of immune B cell proliferation in Germinal Centers (GCs). While this process is critical for bodies to resist infection, it must be carefully regulated. On one hand, not having enough B cells can lead to immunodeficiency and susceptibility to infections. Conversely, inappropriate activation is a major driver of malignant transformation and cancers such as B cell lymphomas. Dr. Pae’s research has the potential to shed light on how lymphomas form and to aid in the rational design of cancer therapeutics.

Project title: "Mechanisms of germinal center B Cell proliferation"
Institution: The Rockefeller University
Named Award: Berger Foundation Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Gabriel D. Victora, PhD
Cancer Type: Blood, Other Cancer
Research Area: Basic Immunology
Fangfei Qu, PhD

Dr. Qu is using Small Cell Lung Cancer (SCLC), a highly metastatic and lethal subtype of lung cancer, as a model to gain a better understanding of brain metastasis. Brain metastases are the most common type of intracranial tumors; they cause morbidity and mortality in a large number of cancer patients worldwide. The lack of preclinical models for brain metastasis has hampered our ability to better understand how primary tumors spread to the brain and grow there. She will first develop in vivo transplant and ex vivo human "mini brain" cancer models to study SCLC metastatic growth in the brain microenvironment. Using these models, she will determine the molecular and cellular mechanisms of metastatic SCLC growth in the brain. This research will suggest new targets for inhibiting growth of SCLC and other cancers at distal metastatic sites in the brain, paving the way for novel treatment approaches for cancer patients.

Project title: "Decoding the molecular and cellular mechanisms underlying the growth of brain metastases"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Julien Sage, PhD
Cancer Type: Other Cancer, Brain, Lung
Research Area: Cell Biology
Romain L. Riscal, PhD

Dr. Riscal aims to identify to identify novel therapeutic strategies that would ultimately benefit most “Clear cell renal cell carcinoma” (ccRCC) patients. Because of obesity and an aging population, the incidence of ccRCC has steadily risen over the last decade. If ccRCC is detected early and can be surgically resected, five-year survival rates are relatively favorable. However, metastatic disease has a catastrophic five-year survival rate of less than 10%. At that stage, treatments are sometimes ineffective due to the established resistance of ccRCC to conventional therapies. Dr. Riscal has found consistent changes in cholesterol metabolism in renal tumors compared to healthy kidney and is currently exploring whether cholesterol dependency of ccRCC could be a promising targetable liability.

Project title: "Exploiting Cholesterol metabolism as a liability in clear cell Renal Cell Carcinoma ( ccRCC)"
Institution: University of Pennsylvania, Philadelphia
Award Program: Fellow
Sponsor(s) / Mentor(s): M. Celeste Simon, PhD
Cancer Type: Other Cancer
Research Area: Cell Biology
Jay F. Sarthy, MD, PhD

Dr. Sarthy is developing new easy-to-use and affordable methods for studying DNA packaging and epigenetics (modification of gene expression) in pediatric cancers with a special focus on diffuse midline gliomas and neuroblastoma. These methods may help explain the drivers of pediatric malignancies and allow clinicians to better monitor response to treatment with the goal of developing new drugs that restore the cell’s ability to package DNA correctly.

Project title: "Characterization of the epigenomic landscape of diffuse midline gliomas"
Institution: Fred Hutchinson Cancer Research Center
Award Program: Sohn Fellow
Sponsor(s) / Mentor(s): Steven Henikoff, PhD, and James Olson, MD, PhD
Cancer Type: Blood, Other Cancer, Pediatric, Brain
Research Area: Epigenetics
  • You can support our innovative researchers.