Medoff Laboratory: Benjamin Medoff, MD

Overview

The Medoff Laboratory at Massachusetts General Hospital studies the pathogenesis of pulmonary inflammation, specifically the role of T cells in mediating inflammatory lung diseases. Using genetically modified mice in various models of lung disease, as well as translational studies in humans with various lung diseases, we study mechanisms of T cell activation and function in the context of these disorders. As a result of this work, we hope to delineate some of the molecular mechanisms involved in the development of lung inflammation. In addition, we hope to reveal novel aspects of lung immune biology and potential therapeutic targets for these disorders.

Research Projects

T Cell Activation/Regulation

Regulators of T cell activation and function. This research program has focused on the mechanisms that control T cell activation and effector functions in asthma, pulmonary infections and lung transplantation. Specifically, we have utilized murine models of disease, genetically modified mice, cellular immunology and translational human studies to characterize the role of effector and regulatory T cells in health and disease. This includes demonstrating the importance of CARMA1 in the development of allergic airway inflammation and regulatory T cell development, the role of Tim3 in modulating the response to influenza infection and transplant rejection, and the role of Mst1 in T cell development and activation.

Innate-Adaptive Immune Interactions

The role of epithelial cell and innate immune cells in airway inflammation. It is now clear that the airway epithelium is a key modulator of the immune response in the lung through its interactions with innate immune cells such as dendritic cells and innate lymphoid cells. My research program has looked at the role of the airway epithelium and dendritic cells in the establishment of the adaptive immune response in allergic airway inflammation. Using animal models of disease and in vitro assays we have established a critical role of CARMA3 for the immune response to allergens in the lungs. Specifically, CARMA3 mediates the production of inflammatory cytokines by airway epithelial cells in response to allergens and other mediators, leading to dendritic cell activation. In other work we have established the key role for dendritic cells and macrophages for the recruitment of neutrophils and T cells into the lung.

Translational Human Studies in Lung Immunology

For over 10 years, our lab had a translational research program that seeks to use human samples from the lung to determine the pathogenesis of various inflammatory lung disease. The program was initially focused on defining the mechanisms of T cell recruitment and activation in the lungs of human subjects with allergic asthma, HIV and COPD, and after lung transplantation. More recently we have started studies focused on defining the innate immune cell profile and changes in epithelial cell functions in the human lung in health and disease. Samples are obtained from human subjects using bronchoalveolar lavage and airway brushings, and the samples are studied using advanced flow cytometry, CyTOF, RNA sequencing and in vitro cellular assays. The subjects are further classified using advanced imaging techniques such as HRCT-PET and optical coherence tomography to better define their pulmonary anatomy and physiology.

Lab Members

Principal Investigator

Benjamin Medoff, MD Principal Investigator, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital Chief, Pulmonary and Critical Care Unit, Massachusetts General Hospital Associate Professor of Medicine, Harvard Medical School

Other Lab Members

Junior Faculty:
Katharine Black, MD
Rachel Knipe, MD

Postdoctoral Fellows:
Jehan Alladina, MD
Tristan Kooistra, MD
Yang Yang, PhD

Research Technicians:
Elizabeth Abe
Dilanjan Anketall
Amanda Logue
Gina Pronzati
Jillian Spinney

Publications

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