THE PROGRAM

The Program in Dermatopathology is directed by George F. Murphy, M.D., Professor of Pathology at Harvard Medical School. The Program is located at Boston’s Brigham and Women’s Hospital (BWH) and 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 skin immune dysfunction and melanoma virulence, with the ultimate goal of bringing discoveries from bench to bedside – in so doing, benefiting those afflicted with various forms of dermatitis and potentially fatal forms of skin cancer. The Program’s research laboratories are complemented by talented and devoted junior faculty, post-doctoral fellows, technologists, and administrators. Funded by federal grants and through collaborations with biotechnology, the team continuously strives to expand its existing base in order to accelerate translationally-relevant progress and discovery. The diagnostic division is composed of a team of five full-time academic dermatopathologists and is responsible for evaluation of thousands of skin biopsies and excisions annually. It serves all of the BWH clinics and the Dana Farber Cancer Institute, and provides consultations for material submitted for second opinions both nationally and internationally. Educational initiatives include the programmatic direction of the Harvard Fellowship in Dermatopathology, co-direction of the annual Harvard CME Course in Dermatopathology, and global outreach to underprivileged communities, including Rwanda, who benefit from dermatopathology expertise and instruction.

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 integration of the Lab with the diagnostic and educational resources of the BWH Program in Dermatopathology produces a unique blend that supports application of state-of-the-art investigation to the most pressing clinical issues that impact on skin health and disease.

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 immunodermatologyLI inset
  • Molecular biology
  • Cancer biology
  • Cutaneous immunology
  • Epigenetics

Cutting-edge routinely available technological approaches include:

  • Immuno-guided laser capture microdissection
  • Quantitative real time RT-PCR analysis
  • Computer-assisted morphometry
  • Humanized murine xenograft models
  • Tissue microarray development
  • NanoString gene profiling
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. Skin is one of the most potent immune organs, one capable of being harnessed to reject melanoma. However, the very immune system that might one day accomplish this feat, when dysfunctional, can itself produce life-threatening inflammation. 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?
  • How can understanding immune dysregulation, as occurs in disorders like graft-versus-host disease and face transplant rejection, provide new insights into therapeutic manipulation of immune cells to inhibit graft rejection, or alternatively, enhance anti-tumor immunity?
THE ADVANCES

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

  • The identification and targeting of melanoma stem cells responsible for tumor virulence (Nature, with Frank Lab)
  • The discovery and/or further elucidation of melanoma biomarkers, such as SOX2 (Am J Pathol) and Nestin (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)
  • Pioneering how reversible epigenetic alterations control melanoma virulence (Cell, with Lian and Shi Labs)
THE ACKNOWLEDGEMENTS

None of the Lab’s activites are possible without active support. We are 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. We also are thankful to be involved in fruitful collaborations with biotechnology, including Bristol-Myers Squibb and RheaCell. The ability to work as partners with outstanding investigators and their laboratories, including the Lian, Shi, Frank, Pomahac, Orgill, and Geha Labs, has resulted in exciting synergies that drive progress and productivity. And finally, we acknowledge those patients afflicted with the many forms of skin disease we seek to cure – our work would not be possible without their input, and for this, we will always be most grateful.