David E. fisher Laboratory

DAVID E. FISHER, MD, PhD

http://www.massgeneral.org/mghdermatology/staff/fisher.htm

Cutaneous Biology Research Center
Building 149, 13th Street
Charlestown, MA 02129
phone: (617) 643-5428
fax: (617) 726-4189

About David E. Fisher

David E. Fisher is a researcher, clinician and academic, and serves as Chief of the MGH Department of Dermatology, Director of the MGH Cutaneous Biology Research Center and Director of the Melanoma Center at MGH.  He is also  the President of the Society for Melanoma Research, the largest international society dedicated to the study of melanoma.  A professor of Pediatrics at Harvard Medical School, Fisher came to the MGH from the Dana-Farber Cancer Institute (DFCI), where he directed the Melanoma Program.

His research has focused on the molecular mechanisms of melanocyte biology; specifically, the developmental, signaling and transcriptional pathways responsible for human melanomas, hyperpigmentation, albinism and hair graying. Most recently, his work at the DFCI identified the transcription factor, Mitf, as essential for the development of normal melanocytes as well as responsible for cancerous transformations. As a clinician, he has worked to translate these new understandings into advances in diagnosis, treatment and prevention of human diseases related to the skin and associated disorders.

A graduate of Swarthmore College with a degree in Biology and Chemistry, Fisher is also a concert cellist and received a degree from the Curtis Institute of Music in Philadelphia. After completing a doctoral degree at Rockefeller University, he began his medical training at Cornell University Medical College and his residency in Internal Medicine at the MGH. Following the completion of clinical fellowships in both adult and pediatric oncology at the Dana-Farber Cancer Institute and Children's Hospital Boston and his postdoctoral research at MIT's Center for Cancer Research, Fisher joined the DFCI staff.

Research

The Fisher Lab studies cell death and proliferation signals in relation to development and disease, particularly cancer. We attempt to understand critical modes of cell homeostasis with a goal of molecular targeted therapy for human disease.

1. p53, Apoptosis, and Cancer Therapy p53 mutations are the most common genetic aberrancy in human cancer and confer tumor cell resistance to apoptosis by many drugs. We study apoptosis in p53 wild type or deficient tumor cells containing defined oncogenes. In addition we have constructed a cell-free apoptosis assay which recapitulates p53's regulatory role, allowing for molecular dissection and direct biochemical purification of death mediators. These studies have identified key intermediates and several negative modulators of p53-dependent apoptosis which may be targets for cancer drug design.
   
   
2. Control of life and death in melanoma Malignant transformation of melanocytes produces one of the most treatment resistant malignancies in man. We have identified a transcriptional network which regulates melanoma cell survival and proliferation as well as melanocyte differentiation during development. Using diverse methods including mouse models, human tumor expression arrays, and cellular assays, we examine mechanisms through which melanoma cells evade death, with the goal of improving therapy. These studies also include examination of the role of UV in melanocyte biology and carcinogenesis.
   
   
3. Mitf transcription factor family in development & cancer Mitf is a helix-loop-helix factor homologous to Myc, whose mutation produces absence of melanocytes and severe abnormalities in osteoclasts, the cells responsible for bone mineral resorption. Mitf mutations occur in humans with Waardenburg Syndrome, a condition involving pigmentation and deafness,. Mitf acts as a master regulator of melanocyte and osteoclast 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. Their roles in cancer as well as means of targeting them for therapeutic benefit are under active investigation.

Lab Members

Suprabha Devi Technologist
Gillian Fell Graduate Student
Brian Fiske Technician
Adam Friedman Graduate Student
Peter Gordon Research Fellow
Rizwan Haq Research Fellow
Vivien Igras Research Supervisor
Akinori Kawakami Research Fellow
Mehdi Khaled Research Fellow
Carmit Levy Research Fellow
Juying Li Research Fellow
Jue Judy Liu Graduate Student
Eiichi Makino Research Fellow
Devarati Mitra Graduate Student
Kelly O’Hanlon Administrative Assistant
Katey Robinson Graduate Student
Nunciada Salma Research Fellow
Thanh-Nga Tran Research Fellow
Rosa Veguilla Graduate Student
Satoru Yokoyama Research Fellow
Xiansi Zhao Research Fellow