What today is known as the Program in Dermatopathology at Brigham and Women’s Hospital had its inception in 1983, when Dr. Ramzi Cotran, known for the Robbins and Cotran legendary pathology textbook, established the first Diagnostic Dermatopathology Service in the BWH Department of Pathology under Dr. George F. Murphy. The Service subsequently evolved under the direction of doctors Raymond Barnhill and Phillip McKee. In 2004, Dr. Murphy returned to develop a research limb, programmatically rounding out existing excellence in diagnosis and education. Now, the Program in Dermatopathology combines clinical diagnostic services and a variety of educational initiatives, with federally-funded research facilities. The tripartite roles of the program make it a model for academic dermatopathology practice as well as a platform for excellence in comprehensive education in the subspecialty. The Program Laboratories located at 221 Longwood Avenue at the Eugene Braunwald Research Building now have two interactive and complementary components: the Murphy Laboratory and the Lian Laboratory, both dedicated to understanding the molecular, genomic, and epigenomic bases for skin inflammation and neoplasia.
George F. Murphy, MD
About George F. Murphy, MD
Program Director, Harvard Dermatopathology Fellowship
Dr. Murphy and his Program are devoted to combining balanced and synergistic efforts in teaching, research, clinical service, and administration. Regarding investigation, his laboratory has been NIH-funded since 1984, with a longstanding focus involving cellular and molecular pathways that mediate graft-versus-host disease. In addition, a collaboration involving BWH and MIT explores tissue stem cells in the context of wound healing and cutaneous regeneration. A third area of investigation is melanoma stem cell biology. Dr. Murphy also has directed the Pathology Cores for the Harvard SDRC and SPORE in Skin Cancer. His early research received the Benjamin Castleman Award of the International Academy of Pathology, and in 1991, he was recognized by election to the American Society for Clinical Investigation. In 1993, one Murphy Lab study was included in the 50 most significant scientific breakthroughs worldwide by Discover magazine. A recent collaborative interaction with Dr. Markus Frank has fostered the first biomarker identification and targeting of melanoma stem cells (2008 cover article, Nature). Subsequent findings have spawned plans for a future clinical trial supported as a Center for Therapeutic Innovation (CTI) initiative by Pfizer Pharmaceuticals. Dr. Murphy has served as a regular term member of the General Medicine A Study Section for the NIH, and he is actively involved in the training of post-doctoral fellows for careers in biomedical research.
With regard to educational leadership, Dr. Murphy has served as Director of the Dermatopathology Fellowship Program and member of the Medical School’s Committee on Appointments and Promotions (COAP) at the University of Pennsylvania, where we established a national CME course in dermatopathology. At Jefferson Medical College, he was Director for Medical Education in Pathology and the Medical School COAP Chair. At Harvard, he also serves on the academic Promotions and Appointments Committee. He has trained over 100 clinical and basic investigators, and has served as a faculty mentor for Harvard’s Scholars in Clinical Science Program. Dr. Murphy also has served as past President of the American Society of Dermatopathology. He has authored the chapter, “The Skin” in the past 5 editions of Robbins and Cotrans Pathologic Basis of Disease. In addition to other authored/edited textbooks and educational monographs, he has been co-author of the 3rd and 4th editions of the AFIP/UAREP Fascicles, Melanocytic Tumors of the Skin; Non-melanocytic Tumors of the Skin; and the new Inflammatory Disorders of the Skin; and serves as co-editor for Lever’s Histopathology of the Skin.
Regarding clinical expertise and innovation, Dr. Murphy established the first Dermatopathology Service at BWH in 1982. Subsequently, he served as co-director and then director of the Dermatopathology Division and Fellowship at Penn and as the first Herman Beerman endowed chair in Dermatology. In 1996, he establish the Jefferson Center for Dermatopathology, Thomas Jefferson University’s first academic dermatopathology program to include basic research. In April 2004, he returned to BWH to form the BWH Program in Dermatopathology, combining expanded diagnostic and didactic services with NIH-funded research laboratories with the goal of setting a new paradigm for the field of Academic Dermatopathology.
Alvaro C. Laga, MD
About Alvaro C. Laga, MD
Dr. Alvaro C. Laga obtained his M.D. from the Instituto Tecnologico de Monterrey in Mexico, and completed residency training in Anatomic and Clinical Pathology at the Brown University Program in Providence, RI. He subsequently joined our laboratory as a Postdoctoral Research Fellow, and is concurrently pursuing a Masters in Medical Sciences through enrollment in the Scholars in Clinical Science Program at Harvard Medical School. (Read the annual Newsletter of the Scholars in Clinical Science Program at Harvard Medical School). His research interests focus on the identification and characterization of stem cell markers in human skin and its derived tumours, as well as the mechanism(s) of stem cell injury in Graft-versus-host-disease. Dr. Laga is an aspiring dermatopathologist, and he will train as a Dermatopathology Fellow in the Harvard Program upon completion of his research fellowship.
Alvaro C. Laga, MD at PubMed
Christine G. Lian, MD
About Christine G. Lian, MD
Dr. Christine Lian is a trained immunologist, epigeneticist, and dermatopathologist who joined the Program in 2013 and directs the Lian Laboratory component of the BWH Program in Dermatopathology research team. One of her investigative interests is to understand immunological mechanisms in different organ transplants. Clinical evidence demonstrates different rates of rejection with different types of organ transplant allografts. For example, intestinal and skin allografts show increased rates of rejection, indicating that intestinal allografts are uniquely immunogenic. However, the precise immunological mechanisms responsible are largely unknown. Dr. Lian’s early work has shown that highly immunogenic organ allografts, such as intestinal transplants, elicit rejection at least in part due to a strong immune response mediated by CD8+ T cells. Because some biologic therapies that inhibit CD4+ T cell function do not impair CD8+ T cell function to the same degree, she explored alternative strategies for inhibiting CD8+ T cell function, including detailed investigation of several TNF receptor superfamily molecules including CD154, membrane lymphotoxin, 4-1BB, and LIGHT. These experiments not only suggested potential targets for intervention in the immune response to intestinal allografts, but also provided more basic insights into the behavior of CD8+ T cells that may be applicable to other disease processes, such as cancer. Recently, Dr. Lian has analyzed a series of 113 sequential biopsies of full facial transplants, providing findings of potential translational significance as well as biological insights that could prompt reexamination of conventional paradigms of effector pathways in skin allograft rejection. Surprisingly, during active rejection, immune cells spatially associated with target cell injury consisted abundantly or predominantly of lymphocytes of donor origin with an immunophenotype typical of the resident memory T-cell subset. Current dogma assumes that skin allograft rejection is mediated by recipient T cells that attack epidermal targets, and the association of donor T cells with sites of target cell injury raises questions regarding the potential complexity of immune cell interactions in the rejection process. A more histopathologically refined and immune-based biomarker approach to assessment of rejection of facial transplants is now indicated based on this study. Overall, by providing morphological evidence and functional insights into possible mechanisms of highly immunogenic allografts involving intestine and skin, this combined body of work underscores the critical role for further refinements in histopathology and biomarker application to the accurate diagnosis, therapeutic monitoring, and mechanistic understanding of vascular composite tissue transplantation in the future.
In 2005, Dr. Lian also initiated collaborative interactions with Dr. Yujiang Shi at Harvard focused on identification of epigenetic pathways in cancer. This work has pioneering the role of 5-hydroxymethylcytosine (5-hmC) in melanoma biology via a breakthrough study published in 2012 in Cell showing loss of 5-hmC as a functionally-relevant, epigenetic hallmark of human melanoma. Because loss of 5-hmC was shown to regulate melanoma virulence and is reversible through manipulation of the TET pathway, the study has significant translational ramifications. Aside from paradigm-shifting implications for melanoma therapy through epigenetic manipulation, loss of 5-hmC has already has shown translational value as a biomarker relevant to assessing melanocytic dysplasia and identifying melanoma micrometastases in lymph nodes. Dr. Lian has recently reviewed the field of melanoma epigenetics that has rapidly emerged since the Cell paper, and is actively combining studies of melanoma stem cell biology with those concerned with regulation of the cancer stem cell phenotype through DNA methylation. These efforts form the foundation of the Lian Laboratory in the BWH Program in Dermatopathology, one with close thematic alliance with the goals and directives of the Murphy Laboratory.
Complete List of Published Work in MyBibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/collections/public/1-WNnKZ8fJ_RaM4IVdoTrW-Q0/?sort=date&direction=ascending
Fellows & Alumni
About Fellows & Alumni
Camilla Borges Ferreira Gomes, DMD, MS.
Sasha Girouard, MD.
John Huang, MD.
Alvaro Laga, MD.
Allison Larson, MD.
Chung-wei Lee, MD, PhD.
Cecilia Lezcano, MD.
Christine Guo Lian, MD.
Ana Carolina Fragosa Motta, DMD.