Contact Information

Cutaneous Biology Research Center

Charlestown Navy Yard Building 149
149 13th Street
Charlestown, MA  02129

Phone: 617-726-4354

Email: DFisher3@partners.org

David E. Fisher, MD, PhD
Chief of Dermatology Service, Massachusetts General Hospital

Edward Wigglesworth Professor of Dermatology, Harvard Medical School

Chair, Executive Committee on Research (ECOR), Massachusetts General Hospital

Affiliations

Explore This Lab

In the Media

December 2022: Researchers Identify the Hormone that Drives Fatigue After Cancer Radiation Therapy- Press Release

March 2022: Sun Exposure and Melanoma, Sun-Seeking, and Sun Protection: Fact and Fiction- Dermatology Times
March 2022:  Podcast: The Future of Melanoma Research | Futurized - thoughts on our emerging future

December 1, 2021: : Redheads really do have a stronger tolerance for pain than others -  Fox 8 News

August 2021: Researchers identify skin darkening enzyme that could help prevent skin cancers – Healio 
June 2021:  Several News Stories related to a study: Low Vitamin D linked to Opioid Addiction

Research Projects

The Fisher laboratory focuses on mechanistic studies which underlie the biology and pathophysiology of skin and melanoma. Research studies range from molecular analyses of pigment cell biology to risk factors responsible for the formation of melanoma and other skin cancers. The laboratory utilizes deep molecular tools to understand how genes are regulated, how they contribute to cancer formation, and how they may be successfully targeted by drugs in order to improve disease treatments or to prevent disease formation altogether. Several areas of particular focus include 1) the study of redhair, fair skinned pigmentation and the manner in which such individuals are at increased risk for skin cancer; 2) identification and analysis of oncogenes which control melanoma cell survival; 3) discovery of new drugs that affect pigmentation, melanoma survival, and other skin- related effects; and 4) examination of the ways in which a gene called MITF plays a master-regulatory role in specifying the development of pigment- producing cells in the body.

We study cell death, proliferation, and lineage differentiation signals in relation to development and disease, particularly in cancer of pigment cells (melanoma). We attempt to understand critical modes of cell homeostasis with a goal of enhancing therapeutic as well as prevention opportunities for melanoma and other cancers. Areas of particular focus are explained below.

Lessons for Malignancy from Normal Development

We focus heavily on the study of melanocytes, the cells responsible for production of constitutive as well as environmentally responsive pigmentation. This area of research includes examination of the mechanisms transmitting the signals from ultraviolet radiation to the pigmentation machinery in skin. We also study the growth/ survival of benign melanocytic nevi, most of which contain mutations in either BRAF or N-Ras oncogenes. One extreme example, Giant Congenital Nevi, are a common cause of childhood melanoma, and we have modeled this in mice, as well as developed potential topical drug approaches to regressing them. We also study melanocyte death in hair follicles, a process associated with hair graying. Our work led to the identification of pathways linking graying to melanocyte and melanoma survival, offering potential leads for novel therapies.

Technology development is an important component of our work. We now routinely develop melanocytes and keratinocytes from iPS cells, and are actively studying production of Dermal Papilla cells (also from iPS) and utilize novel grafting approaches to produce human genetically controlled models of in vivo skin and hair.

Control of Life and Death in Melanoma

Malignant transformation of melanocytes produces one of the most treatment- resistant malignancies in human cancers. We have identified a transcriptional network that regulates melanoma cell survival and proliferation and melanocyte differentiation during development. Using diverse methods— including mouse models, human tumor omics, and cellular assays— we examine mechanisms through which melanoma cells evade death with the goal of improving therapy. Studies include preclinical and clinical analyses of immunotherapy mechanisms and other novel melanoma treatments. Finally we discovered that UV triggers production of endorphin in skin, leading to sun-seeking behavior. We have also identified vitamin D as evolutionary driver of this response, leading to potentially important implications for opiate addiction.

MITF Transcription Factor Family in Development and Cancer

MITF is a helix-loop-helix factor homologous to Myc, whose mutation in man produces absence of melanocytes. MITF acts as a master regulator of melanocyte development and is targeted by several critical signaling pathways. Recently, members of the MITF family have been discovered as oncogenes in a variety of human malignancies, particularly sarcomas of childhood. We are currently investigating their roles in cancer as well as strategies to target them therapeutically. Detailed mechanistic studies focus on transcription factor interactions with chromatin, and epigenetic control of gene expression.

    Lab Members

    David E. Fisher, MD, PhD
    DFisher3@partners.org 

    • Charles Adelmann, PhD
    • Judith Boozer
    • Jessica Flesher, PhD
    • Sharon K. Germana
    • Allison Greuel
    • Joshua Herron
    • Jennifer Hsiao, PhD
    • Lingjuan Huang*
    • Andrew King, MD, PhD
    • Stephen Ostrowski, MD, PhD
    • Nicholas Theodosakis, MD, PhD
    • Avanthika Venkatachalam PhD
    • Xunwei Wu, PhD

    * PhD Student

    Publications

    Complete List of Dr. Fisher's Published Works

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