THE RESEARCH PROGRAM

The Program in Dermatopathology at Boston’s Brigham and Women’s Hospital/Harvard Medical School is devoted to the tripartite mission of education, service, and research in skin pathology. Research is focused on understanding and controlling mechanisms and pathways responsible for melanoma virulence, with the ultimate goal of bringing discoveries from bench to bedside, in so doing, benefiting those afflicted with this potentially fatal form of skin cancer. The Program’s research laboratories are directed by George F. Murphy, M.D., Professor of Pathology at Harvard, and are complemented by talented and devoted junior faculty, post-doctoral fellows, technologists, and administrators. Funded by numerous federal grants, the team continuously strives to expand its existing base in order to accelerate progress and discovery. The Murphy Lab has served as the nucleus of the Harvard Skin Disease Research Center (HSDRC) Morphology and Cell Analysis Core, and is currently the home of the Harvard Specialized Program of Research Excellence (SPORE) Biospecimen Access and Analysis Core, providing sophisticated technical resources, professional expertise, and educational programs to basic and clinical investigators, with the goal of further growth and development of skin cancer research.

THE ENVIRONMENT

Located in the center of Boston’s Longwood Medical Area, The Murphy Lab is based at the Brigham and Women’s Hospital, a major teaching resource of the Harvard Medical School. The laboratory facilities are thus within the immediate vicinity of both the Medical and Dental Schools, the School of Public Health, the Dana Farber Cancer Center, Boston’s Children’s Hospital, the Beth Israel-Deaconess Medical Center, and the Countway Medical Library. The Lab actively collaborates with numerous investigators, both locally and inter-institutionally, the latter including John Hopkins Medical Institutions, the Sloan-Kettering Cancer Center, and the Massachusetts Institute of Technology.

THE RESOURCES

The faculty and staff of the Murphy Lab have a wide variety of complementary interests and abilities. These include:

  • Diagnostic Dermatopathology (see Education)
  • Immunology and immunodermatology
  • Molecular biology
  • Cancer biology

Cutting-edge technological approaches utilized routinely in the laboratory include:

  • Immuno-guided laser capture microdissection
  • Quantitative real time RT-PCR analysis
  • Computer-assisted morphometry
  • Humanized murine xenograft models
  • Tissue microarray development
THE CHALLENGES

Melanoma is arguably the most virulent neoplasm that occurs in humans, a tumor capable of metastasizing when little larger than a grain of rice. Because melanoma occurs on the skin and therefore is readily subjected to visual and experimental scrutiny, it is an important paradigm for understanding the mechanistic underpinnings of all forms of cancer. Some of the questions in which our Lab is intensely interested are:

  • Are some melanoma cells more virulent than others, and how might they be therapeutically targeted?
  • How do melanomas thwart the natural immune response the body regularly musters against this tumor?
  • What are the key biomarkers of melanoma virulence, and how can they assist in detection and treatment?
  • How can circulating melanoma cells be better detected before they cause permanent harm?
  • How can this knowledge be harnessed to develop targeted approaches that will cure metastatic melanoma?
THE ADVANCES

To this end, we and our collaborators have been fortunate to have made several advances, including:

  • The identification and targeting of melanoma stem cells responsible for tumor virulence (Nature)
  • The discovery and/or further elucidation of melanoma biomarkers, such as SOX2 (Am J Pathol) and BMP7 (Lab Invest)
  • The elucidation of how melanoma cells quell host immune reactions (Cancer Res)
  • Insight into how aggressive melanoma cells provide for their own growth and nutrition (Cancer Res)
  • Detection of circulating melanoma cells using a novel stem cell biomarker (Biochem Biophys Res Commun)
THE ACKNOWLEDGEMENTS

None of the Lab’s activites are possible without active support. In addition to those patients afflicted with melanoma and cutaneous immunity whose tissues have facilitated the advancement of the studies of the Murphy Lab to date, we are also indebted to the following funding venues from the National Institutes of Health: the National Cancer Institute, the National Institute for Arthritis, Muskuloskeletal, and Skin Disease, and the National Heart, Lung, and Blood Institute.