Laboratory of Andrew Luster, MD, PhD
Overview
Research in the Luster lab is varied and has historically focused on chemokines, immune cell trafficking, and resident memory effector and regulatory T cells in regulating tissue immunity. Areas of interest include the role of resident memory T cells in the lung in response to allergens and to respiratory viral pathogens as well to autoantigens in autoimmune disease. 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 resident memory effector and regulatory T cells in type 1 and type 2 immune responses and in autoimmunity.
Research Projects
Resident memory effector and regulatory T cells in type 1 and type 2 immune responses
Resident memory T cells (Trm) are a distinct subset of memory T cells that exhibit unique trafficking patterns and functions. Trm 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 Luster lab are aimed at understanding the role of 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 prevent their development and/or dislodge Th2-Trm from the tissue. For type 1 responses, we study the role of CD4+ and CD8+ Trm 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 CD4+ an CD8+ Trm differentiation, function and maintenance in the lung to develop new vaccination strategies to improve protective immunity at barrier surfaces.
The Luster lab is also investigating tissue regulatory T cells (Tregs) and have found important roles for these cells in regulating the early innate immune response in both type 1 and type 2 responses as well effector Trm in tissue. Projects in the lab are currently aimed at uncovering the roles for antigen-specific tissue Tregs in regulating antigen-specific resident memory effector T cell responses in tissue.
Respiratory viral exacerbations of asthma
Respiratory viral infections (RVI) are the most common trigger of asthma exacerbations, yet the mechanisms driving this clinically significant phenomenon remain poorly understood. Asthma is driven by dysregulated type 2 immunity whereas RVIs induce type 1 responses that are known to suppress type 2 inflammation. Paradoxically, antiviral responses to RVI amplify type 2 inflammation in patients with asthma. We are testing the novel hypothesis that RVI exacerbates allergic inflammation by reprogramming tissue resident Tregs and impairing their ability to suppress type 2 immune responses to allergens.
Trm in autoimmunity
Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by progressive immune cell infiltration of the salivary glands and lacrimal glands, leading to chronic dry eyes and mouth disorder. Recent studies have highlighted the potential role of Trm in driving glandular damage in SjD. We are using SjD as model to study the role of specific chemokine systems, such as CXCR3 and CXCR6, in organizing tissue niches tissues for the differentiation, activation and maintenance of autoimmune Trm.
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 using single cell spatial transcriptomics to determine the role of specific chemokine systems in establishing niches in tissue for the differentiation, activation and maintenance of resident memory effector and regulatory T cells.
Robert Ownbey, MD (1994-1996), Pathologist, Colorado
Eduardo Garcia-Zepeda, PhD (1995-1999), Universidad Nacional Autonoma de Mexico
Howard Kesselman, MD (1995-1997), Pulmonary and Critical Care Physician, Steward Health Care System
Michelle Dziejman, PhD (1996-1998), Associate Professor, University of Rochester School of Medicine and Dentistry
Sylvie Abi-Younes, MD (1996-2000), Allergist, Massachusetts
Alain Sauty, MD (1997-1999), University Hospital Lausanne, Switzerland
Andrew Tager, MD (1997-2005) (Deceased)
Robyn Klein, MD, PhD (1993-2003), Professor, Canada Excellence Research Chair in Neurovirology and Neuroimmunology, Western University in London, Ontario, Canada.
Anuja Mathew, PhD (1999-2002), Scientific Review Officer at the NIH
Fred Lee, M.D., Ph.D. (1999-2004), Clinical Instructor in Ambulatory Care and Prevention, Harvard Vangard Medical Associates.
Gabriele Campanella, PhD (1999-2010), Co-Founder, Wilberforce International School of Poverty Alleviation and Development
Jennifer Dufour, PhD (1999-2001)
Above Brands Medical Director, Global Medical Affairs - Inflammation, Pfizer
Mustapha Si-Tahar, PhD (2000), Director, CEPR, INSERM
Richard Colvin, MD, PhD (2000-2009), Senior Translational Medicine Expert, Novartis
Joseph El Khoury, MD (2000-2005), Associate Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Benjamin Medoff, MD (2000-2006), Chief Emeritus, Division of Pulmonary and Critical Care Medicine Associate Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Shannon Bromley, PhD (2001-2007), Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Terry Means, PhD (2001-2007), Principal Scientist, Immunology Cluster, Sanofi
Fumitaka Hayashi, MD, PhD (2001-2004), Psychiatrist, New York
Carolyn (Fleming) Fruci, MD, PhD (2001-2004), Chief, Pulmonary and Critical Care Division, PrimaCARE
Sabina Islam, MD (2001-2011), Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Christoph Hess, MD, PhD (2002-2004), Professor and Head of Medical Outpatient Department and Immunobiology Laboratory, University Hospital Basel; Professor of Experimental Medicine at the University of Cambridge.
Qian Yuan, MD, PhD (2002-2006), Associate Professor of Pediactirs, Massachusetts General Hospital and Harvard Medical School
Sandra Hong, MD (2002-2003), Chair, Department of Allergy and Immunology, Medical Director of the Food Allergy Center of Excellence, Cleveland Clinic
Peter La Camera, MD (2003-2006), Chief, Division of Pulmonary, Critical Care and Sleep Medicine, Steward Health Care System, Boston, MA
Mieko Fukui, M.D. (2002-2006)
Ed Seung, PhD (2003-2011), Senior Research Investigator, Global Biotherapeutics, Sanofi
Nancy Kim, MD (2003-2004; 2005-2012), Director, Clinical Research, Translational Pharmacology, Merck
Shaza Fadel, PhD (2004-2008), Assistant Professor, Dalla Lana School of Public Health, University of Toronto, Canada
Richard Chou, MD, PhD (2004-2009), Chief, Department of Rheumatology, Baystate Health, MA
Diana Brainard, MD (2004-2007), Senior Director, Clinical Research, Liver Diseases, Gilead Sciences
Zamaneh Mikhak, MD (2004-2011), Senior Director, Clinical Research and Development, Kiniksa Pharmaceuticals
Seddon Thomas, PhD (2005-2007), Staff Scientist. Thermo Fisher Scientific
Banu Karimi-Shah, MD (2005-2006), Medical Officer, Center for Drug Evaluation and Research, US Food and Drug Administration
Paul Hesterberg, MD (2005-2006), Instructor in Medicine, Massachusetts General Hospital and Harvard Medical School
Barry Shea, MD (2006-2009), Assistant Professor of Medicine, Massachusetts General Hospital, Harvard Medical School
Robert Friday, MD, PhD (2006-2011), Chief, Rheumatology, Newton-Wellesley Hospital
Yung Chung, MD (2007-2010), Associate Director, Global Medical Affairs, Genzyme
Manuela Funke, MD (2007-2009), Attending, Pulmonary Medicine, Universitatsklinik fur Pneumologie, Switzerland
Joanna Groom, PhD (2007-2011), Professor, Division Head, Immunology, Walter and Eliza Hall Institute of Medical Research, Australia
Roshi Afshar, PhD (2007-2013), Senior Principal Scientist, Johnson & Johnson
Flavia Castelino, MD (2008-2011), Associate Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Autumn Guyer, MD (2009-2010), Allergist & Immunologist, Memorial Sloan Kettering Cancer Center
Christian Sadik, MD (2009-2012), Professor, Department of Dermatology, Allergy and Venerology, University Hospital Lubeck, Germany
Maud Deruaz, Ph.D. (2009-2019), Associate Director Immunology, GlaxoSmithKline.
Sebastian Unizony, MD (2010-2011), Associate Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Nori Sakai, MD, PhD (2010-2013), Assistant Professor and Vice Chair, Division of Blood Purification, Department of Nephrology, Kanazawa University
Morris Ling, M.D.(2010-2021), Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Elizabeth Sorensen, PhD (2010-2018), Research Scientist, Moderna Therapeutics
Jillian Richmond, PhD (2011-2012), Assistant Professor, Tufts Cummings School of Veterinary Medicine
Anna Wolfson, MD (2015-2016), Instructor, Massachusetts General Hospital
Caroline Sokol, MD, PhD (2012-2018), Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Rachel Knipe, MD (2012-2020), Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Jeff Lian, PhD (2013-2019), Research Scientist, Takeda Pharmaceutical.
Isabella Hirako, PhD (2013-2014), Research Scientist, Instituto René Rachou, Fundação Oswaldo Cruz - Minas, Brazil
Lucas Faustino, PhD (2013-2022), Associate Director, Gastrointestinal & Inflammation Drug Discovery Unit, Takeda
Yoshishige Miyabe, MD, PhD (2013-2018), Professor & Division Chief, St. Marianna University School of Medicine, Japan
Chie Miyabe, MD, PhD (2013-2018), Associate Professor, St. Marianna University School of Medicine, Kawasaki, Japan.
Melvyn Chow, PhD (2014-2019), Senior Scientist, Inzen Therapeutics.
Ben Michael, MBChB, MRCP, PhD (2016-2017), Senior Clinical Research Fellow and Honorary Consultant Neurologist, Institute of Infection and Global Health, University of Liverpool
Rod Rahimi, MD, PhD (2015-2021), Assistant Professor of Medicine, Massachusetts General Hospital and Harvard Medical School
Ahmad Sedaghat, MD, PhD (2015-2016), Associate Professor of Otolaryngology, University of Cincinnati College of Medicine
Aleksandra Ozga, PhD (2016-2021), Marie Curie Research Fellow, ETH Zurich
Mazen Nasrallah, M.D. (2017-2019), Rheumatologist, North Shore Medical Center
Zaida Ramirez-Ortiz, Ph.D. (2017-2019), Assistant Professor, University of Massachusetts Medical School
Jehan Alladina, M.D. (2019-2022), Assistant Professor of Medicine of Medicine, Massachusetts General Hospital and Harvard Medical School
Laura Bricio Moreno, Ph.D (2018-2022), Senior Scientist - Moderna
Pritha Sen, M.D. (2019-2023), Instructor in Medicine, Brigham and Women’s Hospital and Harvard Medical School
Michelle Rengarajan, MD, PhD (2019-2024), Instructor in Medicine, Massachusetts General Hospital and Harvard Medical School
Song Chen, PhD (2021-2022), Principal Scientist at Quarry Thera
Ryan Nelson, MD, PhD (2019-2023), Assistant Professor Immunology, University of Minnesota Medical School.
Brandon Law, MD (2023-2025), Director, Early Clinical Development, Bristol Myers Squibb
Publications
Open 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.