GVN Center and Member Spotlight

David Topham

Department of Microbiology and Immunology
University of Rochester Medical Center, URMC
Rochester, USA

What are you and your institution currently working on regarding COVID-19?

The Topham Lab launched a coronavirus research study to understand how the immune system responds to acute COVID-19 infection, including how long immunity lasts once a person has been infected and recovered. We have evidence of pre-existing cross-reactive memory B cells and Original Antigenic Sin in infected subjects. We are also collaborating with researchers at New York University and University of Idaho to examine whether mothers can transmit COVID-19 through breast milk (they don’t) and whether the breast milk itself has immunological properties against the disease (it does). Funded by the Bill and Melinda Gates Foundation and the NIH, the study could result in critical guidance for current and soon-to-be mothers. Physicians at URMC and Rochester Regional Health are investigating a new coronavirus vaccine developed by Pfizer and BioNTech. The URMC Vaccines and Treatments Evaluation Unit is testing Remdesivir combined with other drugs, as well as a Phase III clinical trial of the Astra Zeneca ChAdOX-1 SARS-CoV-2 vaccine. Rochester engineers and medical scientists are collaborating closely with clinicians to develop tests to detect coronavirus. Projects include (1) research on a finger-stick test to detect and study immunity to COVID-19; (2) the creation of tiny sensor chips that use coronavirus proteins to "very quickly" detect the presence of antibodies that help humans fight against the virus; and (3) testing samples of sputum, nasal mucus, or blood using ultrathin silicon nanomembranes to "instantly" determine if an individual has been infected. The Lung Development Molecular Atlas Program (LungMAP) and the Human BioMolecular Atlas Program (HuBMAP) collaboratives received funding from the NIH to examine human lung tissue in order to determine why children seemingly contract COVID-19 at a lower rate and remain more asymptomatic than the older population. Gloria Pryhuber, professor of Neonatology, will lead URMC's involvement in this multi-institutional project. The New York State Emerging Infections Program (EIP) is part of the federal Centers for Disease Control & Prevention's national effort to provide population-based communicable disease data to identify disease patterns, to evaluate vaccine programs, and to identify at-risk populations. The URMC EIP will be performing laboratory and population-based surveillance for COVID-19 as a part of multi-site national study. The group will collect a variety of demographic and clinical data that will be reported to the Centers for Disease Control & Prevention and the Monroe County Department of Public Health.

Please describe your research involving antibodies, memory B-Cells and the S-Subunit?

Dr. Mark Sangster in the Topham Lab has been studying acute and memory B cell (MBC) responses to COVID-19. We found evidence of pre-existing cross-reactive MBC specific for the S2 subunit of the spike glycoprotein and seasonal beta coronaviruses. This cross-reactive MBC responds more rapidly to infection and may affect responses to other SARS-CoV-2 proteins. Antibodies to the S2 subunit can be neutralizing. We are now trying to understand whether this immune memory is correlated with disease outcomes. We are also beginning studies of T cell responses to SARS-CoV-2 in acute and convalescent subjects.

Professional Summary

David Topham joined the faculty at the University of Rochester Medical Center in 1999 and was appointed in 2009 as Vice Provost and Executive Director of the Health Science Center for Computational Innovation (HSCCI), a partnership between New York State, the University and IBM. As Executive Director of the HSCCI, Dr. Topham's responsibility is to support collaboration in biomedical research using High Performance Computational Resources. He will bring together academic biomedical and health-related Research Investigators, High Performance Computational Biologists, and HP Research Computing resources. Dr. Topham provides strategic direction to the HSCCI and facilitates the development of research projects between UR scientists and its corporate partners, as well as support from state and federal agencies.

Dr. Topham is a Professor of Microbiology and Immunology, a member of the David H. Smith Center for Vaccine Biology and Immunology, and directs the New York Influenza Center of Excellence--one of the five national Centers of Excellence in Influenza Research and Surveillance supported by the NIH.

Dr. Topham was recently appointed as the Founding Director of the UR Translational Immunology and Infectious Diseases Institute whose mission is to foster collaborative team based approaches to translational research on infectious diseases and immunology.

About Topham Lab

Viruses that infect the respiratory tract are responsible for extensive morbidity and mortality in human population worldwide. Influenza virus is a particular concern because of its ability to periodically cause deadly pandemics, most recently in 2009 after the spread of a swine-origin H1N1 virus to humans. Novel avian influenza viruses such as H5N1 and H7N9 continue to cause sporadic cases of severe disease in humans and are an ongoing pandemic threat. An understanding of how the immune system controls influenza and other respiratory viruses and provides long-term protection is critical for the rational development of effective vaccination and treatment strategies.

Studies in our lab are primarily aimed at understanding the multiple roles of virus-specific B and T cells in determining the outcome of viral infection of the respiratory tract. In particular, we are interested in the character, longevity, and protective capacity of B and T cell memory induced by infection and vaccination. A large component of work in the lab focuses on the response of the human immune system to infection and vaccination; other work uses a variety of animal model systems to investigate basic immunological mechanisms. A recent initiative in the lab is the identification of viral genes and host responses that influence the severity of respiratory virus infections. This work will identify strategies for engineering new antivirals and improving vaccines.

Many projects involve strong collaborative interactions within centers at the University of Rochester that focus on immunity to respiratory pathogens. These centers include the Respiratory Pathogens Research Center (RPRC), the New York Influenza Center of Excellence (NYICE), and the University of Rochester Genomics Research Center (URGRC).