Skin Cancer

Current Projects
Thomas H. Mann, PhD

Dr. Mann is investigating why the “killer” T cells of our immune system gradually lose the ability to recognize and kill cancer cells. Immunotherapy aims to revitalize these dysfunctional “exhausted” T cells, but a better understanding of how T cells recognize markers on cancer cells called antigens is needed. Dr. Mann is testing the response of engineered T cells to antigen stimulation at different durations, frequencies, and intensities. These studies will focus on understanding the role of calcium signaling in the failure of T cell response. Unraveling the molecular mechanism of T cell exhaustion may help in the design of therapies to prevent or alter its progression, potentially leading to improved immunotherapies.

Project title: "Calcium signaling and the molecular clock of T cell exhaustion"
Institution: The Salk Institute for Biological Studies
Award Program: Fellow
Sponsor(s) / Mentor(s): Susan M. Kaech, PhD
Cancer Type: Skin, All Cancers
Research Area: Tumor Immunology
Trang Nguyen, PhD

Dr. Nguyen is focusing on the key molecular pathways involved in T-cell unresponsive states, which prevents a full immune response against cancer. Within the suppressive cancer environment, T cells stop recognizing and fighting cancer cells. Dr. Nguyen is examining new genes and pathways that activate T cells and overcome the defects of unresponsive T cells. The insights gained from these studies may inspire new therapeutic strategies for cancer immunotherapy.

Project title: "Bypassing the unresponsiveness of T cell anergy and exhaustion"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Arthur Weiss, MD, PhD
Cancer Type: Skin, All Cancers
Research Area: Signal Transduction
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 will focus on a group of 100 patients who develop extreme numbers of this skin cancer, 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. Dr. Sarin works under the mentorship of Jean Y. Tang, MD, PhD, at Stanford University, Stanford.

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
Adam J. Stevens, PhD

Dr. Stevens aims to discover how engineered immune cells may be applied to the treatment of solid tumors that limit the infiltration of endogenous T cells. Dr. Stevens is using protein engineering to design synthetic receptors that direct T cells to tumor-associated antigens and facilitate penetration into the tumor. Once inside the tumor, the engineered cells should serve as signaling hubs to recruit additional immune cells and kill the cancer cells. 

Project title: "Synthetic adhesion molecules: redirecting cell infiltration and organization"
Institution: University of California, San Francisco
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Wendell A. Lim, PhD
Cancer Type: Skin
Research Area: Immunotherapy
Linghe Xi, PhD

Dr. Xi is studying signaling events that drive squamous cell carcinomas (SCCs), a common form of skin cancer. She focuses on WNT signaling, which is an important player in cell fate determination. It appears that WNT signaling is essential for SCC tumor formation, but exactly where and how it is required remains unknown. She is dissecting the activity of WNT signaling during the progression from normal epithelial cells to benign papillomas, and then to malignant SCC tumors. She is also investigating the critical downstream effectors of WNT signaling in this process, in order to identify improved targets for cancer therapeutics.

Project title: "WNT signaling and fate specification of normal versus tumorigenic stem cells"
Institution: The Rockefeller University
Named Award: Dale F. and Betty Ann Frey Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Elaine Fuchs, PhD
Cancer Type: Skin
Research Area: Stem Cell Biology
Yi Yin, PhD

Dr. Yin has developed single-cell assays that will be combined with statistical modeling to understand homologous recombination (HR). Cells use the process of HR to accurately repair harmful breaks that occur on both strands of DNA. Failure to correct such DNA damage can play a role in cancer initiation and progression. Dr. Yin aims to understand this critical mechanism to help guide treatment approaches for many cancer types.

Project title: "Global analysis of DNA break repair by single-cell sequencing"
Institution: University of California, Los Angeles
Award Program: Dale Frey Scientist
Cancer Type: Blood, Breast, Skin
Research Area: Chromosome and Telomere Biology
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