Environmental Influences on the Immune System
Dr. Paige Lawrence
Wright Family Research Professor and Chair, Department of Environmental Medicine
Director, Environmental Health Science Center
Professor of Microbiology & Immunology
University of Rochester School of Medicine & Dentistry
There is considerable evidence that the environment we live in, the foods we consume, the water we drink, the air we breathe, and perhaps even what our parents and grandparents experienced, influences our health and contributes to disease. Yet, how environmental factors do this remains a mystery. Recent studies of an environment sensing transcription factor called the aryl hydrocarbon receptor (AHR) provide several clues about how environmental exposures influence the immune system. Activation of the AHR changes the function of the immune system in human populations and animal models, and some of these alterations persist long after molecules that bind to the AHR are gone. However, the cellular mechanisms that drive these changes remain poorly defined. Using mouse models, we are delineating the root cause of variations in antiviral immune defenses. For example, using conditional knockout mice, bone marrow transplantation, and adoptive transfers, we show that critical changes are due to direct effects in specific types of immune cells, while others are indirect, reflecting alterations to intercellular communication. To delineate causal mechanisms, we combine multidimensional flow cytometry, next generation RNA sequencing, and whole genome assessments of DNA methylation. These approaches have yielded novel information about the cellular pathways affected by early life AHR signaling, including changes in metabolism and mitochondrial function. Functional studies suggest that the AHR influences T cell responsive capacity by promoting a new phenotype in T cells that blends features of senescence and exhaustion. Ongoing studies seek to reveal mechanisms by which early life AHR signaling produces durable changes in immune cell functional capacity, which will provide new insight into approaches to modify immune responses later in life.
B. Paige Lawrence, PhD is the Wright Family Research Professor and Chair of Environmental Medicine, Director of the Rochester Environmental Health Science Center, and Professor of Microbiology and Immunology.
She earned a PhD in Biochemistry, Molecular and Cell Biology, with a minor in Immunology, from Cornell University in 1993. She then joined Dr. Nancy Kerkvliet’s lab at Oregon State University, and embarked on the study of how the environment influences the immune system. Immunotoxicology has remained her passion ever since her postdoc. In 1998, she accepted a tenure track appointment in the College of Pharmacy at Washington State University. She received tenure at WSU in 2004, and was recruited to the University of Rochester in 2006. She was promoted to full professor with tenure in 2012. In 2017, she was selected from a competitive national search to become the new Chair of Environmental Medicine and Director of the Rochester Environmental Health Science Center. She received an endowed professorship in 2019.
Current research in her laboratory focuses on understanding how environmental signals influence the development and function of the immune system. Some of her work focuses on defining how exogenous chemicals shape immunity to infectious agents, including influenza viruses and other respiratory pathogens. Another goal is to discover how environmental signals modify stem cell fate and function, and influence the responsive capacity of the immune system via changes in transcriptional and epigenetic regulatory mechanisms. Central to research by her group is deepening our understanding of how an environment-sensing transcription factor called the aryl hydrocarbon receptor (AHR) regulates the immune system. Yet, her scientific contributions are not limited to the AHR, and include uncovering how endocrine active chemicals modulate the function of the immune system, and how premature birth and hyperoxia impinge on pulmonary immune defenses.
She is very involved in education, research, and service within the institution and nationally. The importance of her contributions is reflected in her publications and awards. For instance, she was recently elected as Fellow in the American Association for the Advancement of Science (AAAS) for her leadership in research to understand how environmental factors influence the developmental programming of the immune system. Also, three different papers from her research group have been selected as Best Paper of the Year by the Immunotoxicology Specialty Section, and another paper was selected as the Best Paper of the Year by the Reproductive and Developmental Toxicology Specialty Section. Moreover, she has had several papers selected as Paper of the Month by the NIEHS, and others selected for editorial highlights by the journal in which they were published.
Her multidisciplinary expertise is highly sought after. For example, she was appointed to a team assembled by the U.S. Institute of Medicine of the National Academies to evaluate the weight of evidence regarding adverse events of 8 different vaccines, which culminated in a report of about 160 vaccine-adverse event relationships. She is an Associate Editor for Toxicological Sciences, and serves on the editorial boards of several other journals, including The Journal of Toxicology and Environmental Health, Toxicology, and The American Journal of Physiology Lung Cellular and Molecular Physiology. She is also very active in the peer review of papers and grants, and also in the Society of Toxicology, holding both elected and appointed positions.
She teaches and mentors undergraduates, graduate students and fellows, and is an active participant in the NIH National Research Mentoring Network, as well as several mentoring programs in Rochester, including an innovative new Mentoring Up program. She is the recipient of three different mentoring awards, as well as a recent award for outstanding leadership of a graduate training program. Moreover, many of the students and fellows who have trained in her lab have received the ‘Best Presentation’ award from the Immunotoxicology, Reproductive and Developmental Toxicology and Molecular Biology Specialty Sections of the SOT, and five graduate students from her lab have received “Young Investigator Awards” from the American Association of Immunologists.
When and Where
1:00 PM-1:50 PM
Thomas Gosnell Hall
Open to the Public