Skin Cancer

Current Projects
Charles H. Adelmann, PhD

Skin cancer is the most common type of cancer worldwide, and sun exposure is known to be one of the main risk factors for developing skin cancers. Melanin pigment gives our hair, eyes, and skin their color, and it also shields skin cells from the carcinogenic effects of sun exposure. Combining just one enzyme (tyrosinase) and two substrates (oxygen and tyrosine) in the lab results in the generation of melanin—yet we know that dozens of other proteins affect pigmentation in humans. How does a process that requires so few components in vitro utilize these other factors in the human body? Dr. Adelmann’s work focuses on the cellular and biochemical contributors to human pigmentation, a clearer understanding of which will facilitate chemopreventative interventions for skin cancer that manipulate or mimic the anti-cancer properties of pigmentation. Dr. Adelmann received his PhD from Massachusetts Institute of Technology and his BA from Rice University.

Project title: "Systematic exploration of the organellar and cellular requirements of pigmentation"
Institution: Massachusetts General Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): David E. Fisher, MD, PhD
Cancer Type: Skin
Research Area: Cell Biology
Madi Y. Cissé, PhD

Dr. Cissé [Merck Fellow] aims to define the functional importance of nutrient sensing within the tumor microenvironment. How cells sense and adapt to the availability of nutrients in their environment is incompletely understood, but one key pathway is the signaling system anchored by the mTORC1 kinase. The mTORC1 kinase regulates cell growth and metabolism in response to nutrients such as amino acids and glucose. Aberrant mTORC1 signaling is implicated in several cancers, including melanoma, known to be heavily influenced by factors in the microenvironment such as nutrient availability. Dr. Cissé aims to understand how tumor metabolism senses and responds to varying nutrient levels, which will be essential for developing novel therapeutic targets.

Project title: "Integration on oncogenic signaling and nutrient sensing by mTOR in tumors"
Institution: Harvard T.H. Chan School of Public Health
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Brendan D. Manning, PhD
Cancer Type: Skin, All Cancers
Research Area: Metabolism
Anita Gola, PhD

Dr. Gola [National Mah Jongg League Fellow] is investigating how tissue regenerates the right cell type, at the right place. Effective cell-cell communication and cell-spatial organization are critical to maintaining organ function and homeostasis. Dr. Gola will use skin as a model tissue to understand how immune cells are organized and how they communicate with resident stem cells while maintaining tolerance and providing protection. When these interactions are disrupted, they can lead to cancers and other hyper-proliferative disorders. Unraveling the mechanisms that govern healthy immune-stem cell crosstalk and what goes wrong in disease may lead to new therapeutics for skin cancers.

Project title: "A spatially patterned stem cell and immune cell barrier at the skin surface"
Institution: The Rockefeller University
Named Award: National Mah Jongg League Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Elaine V. Fuchs, PhD
Cancer Type: Skin
Research Area: Stem Cell Biology
Alexander C. Huang, MD

Immune checkpoint inhibitors (ICI), like anti-PD-1 therapy (αPD-1), have transformed clinical oncology by inducing long-term remissions, even in metastatic disease. However, fewer than 40% of cancer patients achieve such long-term remission with αPD-1, and immune-related toxicity limits more aggressive combined approaches, such as anti-PD1 and anti-CTLA-4 therapy. The question remains why a large portion of the immune response generated by combination immunotherapy is directed towards toxicity rather than anti-tumor immunity. A better understanding of the T-cell response to ICI is needed to develop safer and more effective treatment strategies. In humans, CD8+ T-cells are responsible for anti-tumor immunity. Dr. Huang [Damon Runyon-Doris Duke Clinical Investigator] is investigating the immune responses of different types of CD8+ T-cells to αPD-1 and whether they play a role in determining clinical efficacy and immune toxicity.

Project title: "Shared antigen and neoantigen-specific T cells in checkpoint blockade efficacy and toxicity"
Institution: University of Pennsylvania
Named Award: Damon Runyon-Doris Duke Clinical Investigator
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Gerald P. Linette, MD, PhD
Cancer Type: Skin
Research Area: Immunotherapy
Jordan B. Jastrab, MD, PhD

Immune cells called macrophages can swallow bacteria and contain them in membrane-bound compartments called phagosomes. From inside the phagosome, some bacteria stimulate immune pathways in the cytosol, but it is unclear how immune signals are transmitted across the membrane from the phagosome into the cytosol. To investigate, Dr. Jastrab [Robert Black Fellow] has developed a macrophage infection model using mutants of the bacterium Staphylococcus aureus that stimulate an immune complex in the cytosol called the inflammasome. He aims to identify the host and microbial pathways that facilitate activation of the inflammasome during infection. Because the activation of cytosolic immune receptors by phagosomal bacteria may be important in protection against colorectal cancer, Dr. Jastrab’s work aims to elucidate pathways that may be manipulated to prevent tumorigenesis and enhance anti-tumor immunity. Dr. Jastrab received his MD, PhD from New York University School of Medicine, New York and his BS from Tufts University, Medford.

Project title: "Molecular mechanisms of inflammasome activation by intraphagosomal bacteria"
Institution: Brigham and Women's Hospital
Named Award: Robert Black Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Jonathan C. Kagan, PhD
Cancer Type: Colorectal, Prostate, Skin
Research Area: Basic Immunology
Andrew L. Ji, MD

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the U.S. While most cases are caught early and cured with excision, this cancer is more aggressive in the organ transplant recipient (OTR) population, with higher rates of recurrence and metastasis. Treatment options are severely limited in these cases. OTRs require immunosuppression, which is linked to cSCC aggression, but the underlying molecular and cellular mechanisms are poorly understood. Dr. Ji has discovered an invasive cSCC subpopulation that communicates with non-malignant cell types in the tumor’s environment. By profiling OTR tumors using cutting-edge single-cell and spatial technologies, he aims to better understand how this harmful subpopulation emerges in the immunosuppressed setting, aided by crosstalk with these neighboring cells. His goal is to develop strategies for disabling invasion and improving treatment of cSCC in both OTRs and advanced cases in the general population.

Project title: "Dissecting spatial crosstalk in squamous cell carcinoma arising in organ transplant recipients"
Institution: Icahn School of Medicine at Mount Sinai
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Miriam Merad, MD, PhD
Cancer Type: Skin
Research Area: Genomics
Tamar Kavlashvili, PhD

Mitochondria harbor independent genetic material known as mitochondrial DNA (mtDNA). This compact, circular molecule encodes proteins essential for the assembly of the mitochondrial electron transport chain to generate energy in form of ATP. Like nuclear DNA, mtDNA is susceptible to damage and mutations. One of the most common disease-causing aberrations of mtDNA is termed “common deletion.” This aberration disrupts mitochondrial function, resulting in neuromuscular diseases and potentially certain cancers, including colorectal cancer. Due to a lack of tools to modify the mitochondrial genome, researchers currently do not understand the mechanisms behind common deletion. Dr. Kavlashvili [Timmerman Traverse Fellow] aims to investigate by using cutting-edge molecular biology tools to edit and visualize mtDNA genomes. She will then be poised to unravel impacts of this deletion on various tissues, in order to ultimately mitigate its pathological impact. Dr. Kavlashvili received her PhD from Vanderbilt University, Nashville and her BS from University of Iowa, Iowa City.

Project title: "Developing Tools to Mechanistically Investigate the mtDNA 'Common Deletion'"
Institution: Memorial Sloan Kettering Cancer Center
Named Award: Timmerman Traverse Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Agnel Sfeir, PhD
Cancer Type: Other Cancer, Colorectal, Skin
Research Area: Cell Biology
Siqi Li, PhD

Dr. Li [The Mark Foundation for Cancer Research Fellow] studies signaling events regulating the competition between cells carrying cancer-causing mutations and normal cells during cancer initiation. Previous studies have shown that intercellular signaling between mutant and normal cells could regulate the proliferation of these cells and shape the outcome of cancer initiation. Dr. Li is adapting novel tools to identify what molecular cues are mediating this crosstalk and how they contribute to cancer growth in mouse skin. Understanding these events may guide the development of cancer prevention strategies that restrict the early expansion of mutant cell lines in skin and other tissues. Dr. Li received her PhD from Duke University and her BS from Tsinghua University.

Project title: "Deciphering clonal competition between oncogenic mutant and normal cells and its effect on cancer initiation"
Institution: Fred Hutchinson Cancer Research Center
Named Award: The Mark Foundation for Cancer Research Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Slobodan Beronja, PhD
Cancer Type: Skin
Research Area: Carcinogenesis
Mira A. Patel, MD

One of the leading causes of death from cancer is metastasis, or when cancer spreads from its original tissue to other parts of the body. A gene that all humans carry, called Apolipoprotein E (APOE), plays a role in how our bodies respond to cancer, including risk of metastasis. The gene comes in one of three forms: APOE2, APOE3, or APOE4. Individuals who carry APOE2 tend to fare worse when diagnosed with melanoma, while those who carry APOE4 tend to have a much lower risk of melanoma metastasis and a much better chance of survival. (Those who carry APOE3 fall somewhere in between.) Dr. Patel is researching how APOE expression in immune cells either promotes cancer targeting, as in the case of APOE4, or cancer cell survival, as in the case of APOE2. With a better understanding of how the APOE gene affects the body's response to cancer, she hopes to improve cancer therapy by tailoring treatment to the form of APOE each patient carries.

Project title: "Molecular mechanisms of human APOE-mediated myeloid cell modulation in cancer"
Institution: The Rockefeller University
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Sohail F. Tavazoie, MD, PhD
Cancer Type: Skin
Research Area: Tumor Immunology
Kavita Y. Sarin, MD, PhD

Basal cell cancer (BCC) is the most common cancer in the United States with 2 million cases annually resulting in $5 billion in societal cost. Although the majority of BCCs are small and surgically accessible, some individuals develop frequent recurrences of BCC and suffer from severe disability related to surgery and decreased quality of life. Dr. Sarin [D.G. 'Mitch' Mitchell Clinical Investigator] will focus on a group of 100 patients who develop extreme numbers of this skin lesion, in order to identify the genetic mechanisms that contribute to cancer susceptibility. While most BCCs are thought to develop from DNA damage caused by the sun's ultraviolet rays, a patient's genetics also play a critical role in disease progression. Understanding the mechanisms that contribute to cancer susceptibility will help identify at-risk individuals so they can be monitored for earlier diagnosis and prevention. She also aims to develop new non-surgical therapies for these patients.

Project title: "Genetic contributions and novel therapies for individuals with frequent basal cell cancer"
Institution: Stanford University
Named Award: D.G. 'Mitch' Mitchell Clinical Investigator
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Jean Y. Tang, MD, PhD, and Anthony E. Oro, MD, PhD
Cancer Type: Skin
Research Area: Cancer Genetics
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