Luster Lab: Andrew D. Luster, MD, PhD

Overview

Chemokines, Resident Memory Effector and Regulatory Cells, and Tissue Immunity

Research in the Luster lab is varied and has historically focused on chemokines, immune cell trafficking, and resident memory effector and regulatory cells in regulating tissue immunity.  Areas of interest included the role of resident memory T cells in the lung in response to allergens in the asthmatic lung and to respiratory viral pathogens, such as SARS-CoV-2 and influenza, as well to vaccination.  The role of chemokines in regulating the immune response to tumors and cancer immunotherapy is also studied.  One unifying principle under investigation is determining the role of specific chemokine systems in establishing tissue niches for the differentiation and maintenance of specific T cell populations, such as resident memory T cells in the lung and stem-like CD8⁺ and CD4⁺ T cells in the tumor microenvironment.

Resident memory effector and regulatory cells and tissue immunity.  Distinct subsets of memory T cells that exhibit unique trafficking patterns and functions have been identified.  Recently, we and others have identified a memory T cell subset referred to as resident memory T cells (Trm) that do not recirculate but instead persist in previously inflamed nonlymphoid tissue.  Trm provide the first line of antigen-specific immunity in the tissue and enhanced local immune memory.  Studies in the lab are aimed at understanding the role of both CD4⁺ and CD8⁺ Trm cells in both type 1 responses, such as respiratory viral infections, and type 2 responses, such as allergic asthma.  For a type 2 response, we study the role of Th2-Trm in allergic asthma as we found that these cells drive many of the cardinal features of asthma following allergen re-encounter in the airway.  Projects in the lab are aimed at uncovering the factors and genetic programs that lead to Th2-Trm differentiation, function and maintenance in the tissue with a view to developing new therapies that dislodge these cells from the tissue.  For type 1 responses, we study the role of resident memory CD4⁺ and CD8⁺ T cells in protection from respiratory viral pathogens, such as influenza and SARS-CoV-2.  Projects are aimed at uncovering the factors and genetic programs that lead to CD8⁺ Trm differentiation, function and maintenance in the lung to develop new vaccination strategies to improve protective immunity at barrier surfaces.

We are also investigating tissue Tregs and have recently found important roles for these cells in regulating the early innate immune response in both type 1 and type 2 responses.  Projects in the lab are currently aimed at uncovering roles for antigen-specific tissue Tregs in regulating antigen-specific resident memory effector T cell responses in tissue.

T cell response to SARS-CoV-2.  Studies on SARS-CoV-2 in the lab focus on strategies to increase the breadth and cross-reactivity of the T and B cell response to vaccination to generate a pan coronavirus vaccine.  In addition, vaccine strategies are also being developed to generate more robust resident memory T cell populations in the lung that will offer better protection from infection. 

Cancer immunotherapy.  Chemokines play critical roles in the immune response to cancer and in cancer immunotherapy.  Levels of specific chemokines, such as the CXCR3 ligands CXCL9 and CXCL10, which are of particular interest to the lab, are some of the best predicators of robust and effective anti-tumor immune responses.  Studies are aimed at understanding the role of chemokines in the recruitment of immune cells into tumors as well as the role of chemokines in the interactions of immune cells once within the tumor microenvironment necessary to generate an effective anti-tumor immune response.  Strategies to induce the expression of specific chemokines, such as CXCL9 and CXCL10, in tumors are being pursued to improve the anti-tumor immune response and to jump start the immune response of “cold” tumors to turn them “hot”.

Tissue immune cell niches.  One unifying principle under investigation is determining the role of specific chemokine systems in establishing niches in lymphoid as well as non-lymphoid tissue, such as the lung and tumor microenvironment, for the differentiation, activation and maintenance of specific T cell populations, such as resident memory T cells in the lung and stem-like CD8⁺ and CD4⁺ T cells in the tumor microenvironment.

Research Positions

If you are interested in applying for a postdoctoral position, or are a Harvard PhD student interested in a laboratory rotation, please e-mail your CV (for student and postdoctoral) and reference letters (for postdoctoral) to aluster@mgh.harvard.edu.

Lab Members

Principal Investigator

Andrew D. Luster, MD, PhD Chief, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital Director, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital E. Alexandria and Michael N. Altman Chair in Immunology, Massachusetts General Hospital Persis, Cyrus and Marlow B. Harrison Professor of Medicine, Harvard Medical School

Research Team

Junior Faculty

• Jason Griffith, MD, PhD
• Ryan Nelson, MD
• Michelle Rengarajan, MD

Postdoctoral Fellows

• Juliana Barreto De Albuquerque, PhD
• Brandon Law, MD
• Mateus Lopes, PhD
• Jacquelyn Nestor, MD, PhD
• Amandine Selle, PhD

Lab Manager

• Amy Litman

Research Technicians

• Victoria Cottrell
• Thao Nguyen
• Enrique Rodriguez
• Michelle Yeung

Publications

View a list of publications from this investigator >.