Skin Cancer

Current Projects
Matthew Bakalar, PhD

Dr. Bakalar is developing new methods to discover the millions of interactions between T-cell receptors and foreign antigens that trigger an immune response. In many cancers, such as metastatic melanoma, immunotherapy depends on the ability of T cells to recognize and respond to tumor-specific neoantigens—new proteins found on cancer cells, which let the immune system know that these are not normal cells. Collecting the data on this relationship can help create computational models to predict the antigen-target of a patient’s individual T cell receptor, which could then guide the design of patient-specific cancer vaccines and engineering of new, tumor-targeting T cells.

Project title: Predicting the interactions of T cell receptors with peptide-MHC complexes
Institution: The Broad Institute of MIT and Harvard
Award Program: Fellow
Sponsor(s) / Mentor(s): Nir Hacohen, PhD
Cancer Type: Skin, All Cancers
Research Area: Basic Immunology
Michael E. Birnbaum, PhD

Immunotherapies that rely on reinvigorating T cells to patrol the body, detect cancerous cells and eliminate them have shown the potential for long-lasting cures. Despite their initial success, immunotherapies have been effective only for some cancers and for some patients. To improve outcomes, Dr. Birnbaum has developed a new method to match T cells with their antigen targets on cancer cells by engineering viruses to use T cell recognition as a means of cell entry. This technology will be applicable to a wide range of cancers, including ones for which immunotherapy is not currently effective.

Project title: "Decoding and reprogramming tumor-infiltrating T cells by pMHC-targeted lentiviruses"
Institution: Massachusetts Institute of Technology
Award Program: Innovator
Cancer Type: Skin, All Cancers
Research Area: Immunotherapy
Aleksey Chudnovskiy, PhD

Dr. Chudnovskiy studies “antigen presentation,” an immune process by which dendritic cells capture antigens at the tumor site, migrate to the tumor-draining lymph nodes, and present tumor antigens to the effector CD4 and CD8 T cells that are responsible for anti-tumor responses. This is the first crucial step in successful cancer immunotherapy.

Project title: "Defining dendritic cell-T cell interaction history within the tumor microenvironment using enzymatic labeling"
Institution: The Rockefeller University
Award Program: Fellow
Sponsor(s) / Mentor(s): Gabriel D. Victora, PhD
Cancer Type: Lung, Skin
Research Area: Basic Immunology
Nicholas C. DeVito, MD

Immunotherapy has resulted in positive outcomes for patients with melanoma, lung cancer, and other malignancies; however, most patients do not have meaningful responses to this treatment strategy. Tumors that fail to respond to immunotherapy have effectively hidden themselves from detection by the host immune system. Understanding how cancers create an immune-excluded environment promises to lead to the development of more highly effective immunotherapies. Dendritic cells (DCs) play a central role in orchestrating the immune response to cancers by enabling T cells to “see” and destroy cancerous cells. Previous work has shown that melanomas secrete a protein called Wnt5a that potently suppresses DC function and ultimately contributes to the development of immunotherapy resistance. Dr. DeVito will examine certain tumor signaling pathways that have been implicated in driving Wnt5a production and facilitating cancer spreading by suppressing DC function within nearby draining lymph node tissues, which are critical for generating immune responses capable of destroying developing cancers. These studies will further investigate the ability of Wnt5a inhibition to sensitize cancers that are typically resistant to immunotherapy strategies. In addition, he is conducting a clinical trial to determine if the activation of these pathways correlates with immunotherapy failure in melanoma patients. He anticipates that better characterization of pathways that cancers utilize to suppress DC function to thus shut down the immune response will lead to the discovery of novel, more effective immunotherapy strategies, and may identify biomarkers that will improve selection of tailored immunotherapies for specific cancer patients.

Project title: "Investigating the role of EMT-mediated dendritic cell tolerization in checkpoint inhibitor resistance"
Institution: Duke University
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Brent A. Hanks, MD, PhD
Cancer Type: Lung, Skin
Research Area: Tumor Immunology
Xintong Dong, PhD

Dr. Dong studies how injury and pathogen invasion trigger a chain of inflammatory and repair responses that restore the damaged tissue. Defects in wound repair result in painful, non-healing ulcers that frequently affect aged individuals and diabetes patients. Malignant tumors are particularly severe complications, which often occur at sites of repetitive irritation and chronic wounds. She is investigating the roles of anti-microbial peptides during inflammation and wound healing, and hopes that these studies will provide insights about the cause and prevention of various carcinomas.

Project title: "Investigating ligand-receptor interactions between defensins and mrgprs in cutaneous inflammation and wound healing"
Institution: The Johns Hopkins University School of Medicine
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Xinzhong Dong, PhD
Cancer Type: Skin
Research Area: Basic Immunology
Gabriel K. Griffin, MD

Immunotherapy drugs, which spur the body's own immune system to attack tumors, hold great promise but still fail in many patients. Dr. Griffin aims to identify therapeutic targets that can enhance the efficacy and scope of immunotherapy in melanoma and other cancer types. His unique approach focuses on retrotransposons, repetitive sequences of DNA that are evolutionary remnants of viruses and comprise upwards of 50% of the human genome. These genetic elements are usually silenced via DNA methylation but can activate an immune response at certain times. Dr. Griffin’s research will characterize the epigenetic pathways that silence these repetitive elements in cancer cells, thus helping tumors evade surveillance by the immune system. This basic understanding may guide the development of epigenetic therapies capable of triggering anti-tumor immunity.

Project title: "Enhancing cancer immunotherapy through epigenetic modulation of the repetitive genome"
Institution: Brigham and Women's Hospital
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Bradley E. Bernstein, MD, PhD, and Arlene H. Sharpe, MD, PhD
Cancer Type: Skin
Research Area: Epigenetics
Megan Insco, MD, PhD

Dr. Insco studies advanced melanoma. Melanoma initiation and drug resistance rely heavily on factors that control gene expression. Proteins called Cyclin Dependent Kinases (CDKs) show promise as drug targets in multiple difficult-to-treat cancers and are enabling a method to “drug” the previously “undruggable” process of gene expression. She aims to determine whether any of the transcriptional CDKs could be an effective drug target in advanced melanoma. 

Project title: "Investigating transcriptional cyclin dependent kinases as novel melanoma drug targets"
Institution: Boston Children's Hospital
Named Award: William Raveis Charitable Fund Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Len Zon, MD
Cancer Type: Skin
Research Area: Animal Models/Mouse Models
Warakorn Kulalert, PhD

Dr. Kulalert focuses on how the skin is influenced by microbes. The skin is enriched with immune cells and highly innervated; nevertheless, the roles of neuroimmune crosstalk in cancer development and treatment remain largely unexplored. Sensory perception, especially pain sensation, is associated with cancer-related complications as well as chemotherapy. Because the microbiota plays a critical role in maintaining tissue homeostasis in the skin, he will explore whether sensory processing can also be modulated by the host-microbe interactions, particularly in the context of tumorigenesis and cancer treatment. These insights may provide novel tools to alleviate tumor progression and complications linked with cancer and chemotherapy, including pain sensation. 

Project title: "Characterization of the microbiota-mediated cutaneous neuroimmune interface and its impacts on tumorgenesis and cancer therapy"
Institution: National Institutes of Health
Award Program: Fellow
Sponsor(s) / Mentor(s): Yasmine Belkaid, PhD
Cancer Type: Skin
Research Area: Basic Immunology
Xiaochun Li, PhD

Dr. Li is focusing on the Hedgehog (Hh) signaling pathway, which is required for proper development during the formation of an embryo. This pathway can also be activated abnormally in adult tissue and has been implicated in multiple cancers—including basal cell carcinoma and medulloblastoma—that account for about 25% of cancer deaths. His lab will apply structural and cell biological approaches to study two major components of the Hedgehog signaling pathway: Patched-I, a tumor suppressor, and Smoothened, an oncoprotein. These results will broaden the understanding of the Hh pathway in cancer progression and may help identify potential targets for therapeutic intervention.

Project title: “Investigations on Patched, a tumor suppressor, and its regulation in Hedgehog pathway”
Institution: University of Texas Southwestern Medical Center
Award Program: Innovator
Cancer Type: Skin
Research Area: Structural Biology
Piro Lito, MD, PhD

Therapies that directly target cancer-promoting oncoproteins have revolutionized the treatment of cancer. Cancers, however, are primed to adapt and evolve in the presence of treatment, resulting in an ability to resume growth despite the presence of therapy. Utilizing cutting-edge new techniques that allow the determination of genetic alterations in single cancer cells, Piro aims to understand the principles that govern the evolution of resistance during therapy and identify novel therapeutic interventions that halt this process. His specific focus will be on resistance of lung cancer and melanoma to BRAF-targeted therapies. 

Project title: "Modeling the evolution of resistance to ERK signaling inhibitors at the single cell level"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Neal X. Rosen, MD, PhD, and Charles M. Rudin, MD, PhD
Cancer Type: Lung, Skin
Research Area: Experimental Therapeutics
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