SUMMARY
The research goal of Jorg Goronzy, M.D., Ph.D., is to understand the effects of age on the immune system. Dr. Goronzy's laboratory studies how functional fitness and diversity of the T lymphocyte system are maintained over the course of a lifetime, how T cell memory is generated after infection and vaccination, and how immune aging makes people susceptible to cancer, infection and chronic, low-grade (smoldering) inflammation. In addition, his research team is defining mechanisms by which immune aging contributes to autoimmune diseases such as rheumatoid arthritis and giant cell arteritis.
Dr. Goronzy's studies start with ex vivo systems of human peripheral blood cells to identify age-associated molecular and epigenetic signatures in T cell responses. Then, his team uses in vivo models to determine the mechanisms and functional relevance of these signatures. Ultimately, he aims to identify molecular pathways that scientists can target to delay T cell aging or to improve immune responses to viral infections and vaccinations in older age.
Focus areas
- Mechanisms controlling the size and functionality of the T cell system. Adaptive immune responses depend on a T cell repertoire that is functionally balanced and has a diverse set of T cell receptors. However, T cell generation peaks at puberty and then rapidly declines. Additionally, T cell homeostasis can be threatened by T cell loss and oligoclonal T cell expansion in response to persistent pathogens. For example, some people have massively inflated T cell responses due to latent infection with cytomegalovirus. Dr. Goronzy's team is defining mechanisms that maintain T cell numbers, diversity and functional fitness despite aging or chronic infection.
- Regulation of T cell activation and differentiation with age. Dr. Goronzy examines how age-associated changes in signaling and metabolic pathways interfere with T cell epigenetics. He also investigates how such changes shape the differentiation into functional T cell subsets, including T follicular helper cells that are needed for antibody production, T effector cells that cause inflammation and long-lived memory T cells that that protect the body.
- Mechanisms supporting longevity of immune memory. Dr. Goronzy's lab examines the epigenetic and transcriptional properties of virus-specific memory T cells at the single-cell level. Such properties allow the cells to be long-lived, a prerequisite for lasting immune protection from vaccinations.
- Inflamm-aging. Aging is associated with a systemic low-grade inflammatory state — referred to as inflamm-aging — that causes widespread organ dysfunction. Dr. Goronzy's team studies how T cell defects contribute to inflamm-aging.
- Age as a risk factor for autoimmune disease. Dr. Goronzy's research team investigates how age-associated changes in the genome and epigenome of T cells prevent the immune system from protecting the body from autoimmune diseases such as rheumatoid arthritis.
Significance to patient care
By advancing the understanding of how the immune system ages, Dr. Goronzy aims to identify ways to delay immune aging or compensate for age-associated immune defects.
Professional highlights
- Immune Aging Award, for “Divergent Effect of p16 and p21 on the SASP and T-Cell Surveillance of Senescent Cells,” Department of Immunology and Robert and Arlene Kogod Center on Aging, Mayo Clinic, 2024.
- Professor of Medicine, Stanford University School of Medicine, 2010-2021.
- Director, Division of Rheumatology, Emory University School of Medicine, 2007-2009.
- Director, Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, 2004-2009.
- Mason I. Lowance, M.D., Professor of Medicine, Emory University School of Medicine, 2004-2009.
- Elected to the Association of American Physicians, 2002.
- Outstanding Investigator Award, Department of Medicine, Mayo Clinic, 1998.
- Department of Medicine Outstanding Investigator Award, Mayo Clinic Foundation for Medical Education and Research, 1998.
- Elected to the American Society for Clinical Investigation, 1994.
- Henry Kunkel Young Investigator Award, American College of Rheumatology, 1992.