Massachusetts General Hospital

Basic & Translational Research Opportunities

The optimal training for a career that will encompass both funded research and clinical service is to combine the required 2-1/2 years of AP or CP clinical training with a two or three year fellowship in basic or translational research. The department aims to encourage, mentor and support trainees committed to this career path through the Specialized Pathologist-Laboratory Investigator (SP-LIT) Program.

Residents interested in laboratory research consult with Dr. Louis or Dr. Frosch early in their training to obtain advice on selecting a laboratory and a research mentor. Research may be done in any of the Pathology Department research laboratories, in other laboratories at MGH, Harvard, or M.I.T. They work with the mentor to develop a research plan and typically apply for an individual NIH fellowship. Research may begin after 2-1/2 –3-1/2 years of AP, CP or AP/CP training; a program can also be developed to include training in one of the departmental ACGME-accredited subspecialty fellowship programs.

Residents are supported by the departmental NIH T32 Training Grant (7 positions) or individual fellowships. Residents and fellows regularly present their research results at national and international meetings and publish their studies in respected peer-reviewed journals, e.g., Cell, Science, Nature, Cancer Cell, Developmental Cell, Molecular Cell, Nature Genetics, Current Biology and PNAS. The Molecular Pathology and Research (MPR) Conference provides weekly updates on research issues, particularly those that relate to pathology. Pathology Grand Rounds highlights the research opportunities at MGH and at other institutions by visiting faculty.

Research Facilities

The department is currently in the process of major expansion of its research space and program. The department has over 20,000 square feet of research laboratory space, primarily divided among two major facilities in MGH-East/Lawrence A. Martin Research Laboratories in Charlestown (10 minutes by shuttle bus) and the Simches building on the main MGH campus. The department is currently expanding its research portfolio extensively, with over 10,000 square feet of research space slated to be filled with new scientific recruits over the next few years. The laboratories are well-equipped for molecular, biochemical, animal modeling, genomic, immunological and ultrastructural studies. Current Pathology research is supported by an annual budget of approximately $8,000,000 in research and training grants, principally from the NIH, awarded to members of the department. The program is expanding rapidly, with a number of new RO1-level grants over the past two years alone. The research faculty now includes over 20 faculty and numerous postdoctoral fellows. Additional clinical investigations are carried out in the Anatomic and Clinical Pathology units of the department.

Primary Research Interests

Major areas of investigation include the molecular pathogenesis of neoplasia, including clinical-pathologic correlation, molecular genetics, and cell biology of malignant lymphomas, breast cancer and CNS tumors; the classification and evaluation of prognostic factors in breast cancer, ovarian carcinoma, lymphoproliferative diseases, bladder cancer, pulmonary tumors, bone and soft tissue malignancies, and malignant melanomas; oncogene expression and flow cytometric analysis of human tumors; immunological mechanisms in diseases of the kidney and gastrointestinal tract; the pathogenesis and therapy of allograft rejection; T cell differentiation pathways; function of adhesion molecules, and other T cell surface components; the biologic function of dendritic cells, Kupffer cells, and alveolar macrophages; lipid metabolism in platelets; ethanol induced esterification; biology of cell junctions; the use of molecular biological probes to study human disease (in situ hybridization, polymerase chain reaction, laser capture microdissection, expression array analysis); cell biology of lung cells and accessory cell function of dendritic cells; molecular etiology and pathogenesis of Alzheimer's and Huntington's diseases. These programs often involve collaborative research with investigators in other departments at the MGH, Harvard Medical School or the Massachusetts Institute of Technology.

Recent high-profile publications from Molecular Pathology include:

• Smith AC, Raimondi AR, Salthouse CD, Ignatius MS, Blackburn JS, Mizgirev IV,Storer NY, de Jong JL, Chen AT, Zhou Y, Revskoy S, Zon LI, Langenau DM.High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia. Blood. 2010 Apr 22;115(16):3296-303.

• Adli M, Zhu J, Bernstein BE. Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors. Nat Methods. 2010 Jul 11. [Epub ahead of print] PubMed PMID: 20622861.

• Aiden AP, Rivera MN, Rheinbay E, Ku M, Coffman EJ, Truong TT, Vargas SO, Lander ES, Haber DA, Bernstein BE. Wilms tumor chromatin profiles highlight stem cell properties and a renal developmental network. Cell Stem Cell. 2010 Jun 4;6(6):591-602.

• Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallace E, Sander JD, Müller-Lerch F, Fu F, Pearlberg J, Göbel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB Jr, Cathomen T, Voytas DF, Joung JK. Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell. 2008 Jul 25;31(2):294-301.

Clinicopathologic Research

Residents are presented with numerous opportunities for clinically oriented and translational research in all fields of pathology, as they work and learn with our staff of sub-specialized academic pathologists; our program strongly encourages residents to be involved in such projects. Often such involvement arises in the context of clinical cases encountered in the course of clinical training. Alternatively, a resident may be approached by a staff pathologist who has a project that seems to correspond to an area of mutual interest. Residents are frequently the driving force behind such projects and deservedly become the primary investigators. They work closely with the staff member in discussing the goals of the project, aggregating the materials and developing the methods, reviewing the findings and drawing the conclusions that will lead to the final manuscript. In many instances, these projects are presented as a platform or poster by the resident at national or international meetings and often result in publications in highly regarded, peer-reviewed journals. Many of these publications involve collaborations with other departments within MGH and at other institutions. Senior residents and fellows have been presenters and authors in the Case Records of the MGH, which are published in the New England Journal of Medicine.

Recent high-profile clinicopathologic publications by MGH residents and fellows (residents/fellows' names in boldface):

• Turbiner J, Amin MD, Humphrey PA, Srigley JR, De Leval L, Radhakrishnan A, Oliva E. Cystic nephroma and mixed epithelial and stromal tumor of the kidney: are they one and the same entity? A clinicopathologic study of 34 cases. Am J Surg Pathol. 31:489-500, 2007.
• Farris AB, Hasserjian RP, Zukerberg LR, Amrein PC, Greene RE, Mark EJ, Kradin RL. Diffuse Cellular and Fibrosing Insterstitial Pneumonitis with Desquamative Interstitial Pneumonitis-like Features Associated with Myeolid Neoplasia. Am J Surg Pathol. 2009 Aug 3.
• Kim JY, Lewandrowski KB. Point-of-case testing informatics. Clin Lab Med. 29:449-461, 2009.
• Staropoli JF, Van Cott EM, Makar RS. Membrane autoantibodies in systemic lupus erythematosus: a case of autoimmune hemolytic anemia, antiphospholipid antibodies, and transient acquired activated protein C resistance. Transfusion. 48:2435-2441, 2008.

Updated 11/18/2010
Navigation 12/13/2011