Ph.D. in Pharmacology and Biochemistry, Baylor College of Medicine, 1975
Molecular Genetics and Biochemistry, Cellular Molecular Biology and Physiology, Molecular Genetics/Cell Physiology
Host: Pathogen relationships, innate immune defenses against zoonotic viruses, adaptive immune defense, including humoral and cellular defenses, virus pathogenesis, neuropathogenesis, neuroimmunology, neurogenomics, therapeutics (drug discovery) and vaccine designs, rapid pathogen identification, high-throughput diagnostics, models of natural versus foreign host infection, FTIR spectroscopy, and high-content screeing.
Pathogen Interactions in Natural and Foreign (Zoonotic) Hosts During Nonhuman Primate Alphaherpesvirus Infections of Primary Target Cells and Within the Cells of Peripheral and Central Nervous Systems. The principal focus of our laboratory is to increase our understanding of the dynamic interactions between B virus (Macacine herpesvirus 1) and the natural and foreign hosts it infects. The earliest host responses to virus infection consist of innate defenses, which ultimately result in a directed adaptive defense responses of host cells. Viruses can redirect or block these responses effectively particularly when virus and host species have not had the opportunity to co-adapt together. When there has been little or no co-evolution, there is often a lack of orchestrated activity essential for survival of both the host and the virus or successful endosymbiotic relationship. Scientific investigators often focus on such viruses because they generally result in the demise of the infected host and the concomitant negative economic impacts caused by morbidities and loss of lives. B virus is studied in our laboratory as the model of a foreign versus natural host infections. We have similarly studied baboon reovirus, an agent discovered in our laboratory and found to be the etiologic agent of encephalitic disease in baboons from both captive colonies and in the wild. Understanding the mechanisms by which viruses invade the central nervous system and host actions that control this invasion serves to inform the rational design of successful intervention strategies for therapeutics and vaccines. Our early studies were designed to better understand B virus structure and identify differences between this unique zoonotic virus and its relatively innocuous alphaherpesvirus family members. B virus is the only member of the genus Herpesviridae that causes zoonotic infections, killing up to 80% of untreated humans. Fortunately zoonotic infection is rare, observed primarily in occupational settings where humans have close contact with macaques but when these infections occur our laboratory collects isolates and studies pathogenesis utilizing peri-mortem and post mortem samples to better understand the pathways utilized by B virus to invade the human brainstem in cases when therapeutic intervention fails. Our laboratory also provides laboratory support for survivors of B virus zoonosis, which ultimately informs the mechanisms responsible for latency and reactivation differences in natural versus foreign hosts. For much of our research we utilize primary cell culture models as well as small animal models of disease to better characterize cell:virus (host:pathogen) interactions, including innate and adaptive defenses that are recruited/redirected during the course of infection. For these studies we utilize co-cultivation techniques, real-time microscopy, and high-content intracellular screening technologies. Additionally, we continue to design and study enhanced strategies for early identification of infection in both humans and nonhuman primates and mechanisms by which zoonotic infections can be successfully treated/prevented because B virus is a grave occupational hazard in research facilities using macaque monkeys for biomedical research. Further, application of novel diagnostic technologies provide critical insight about the challenges of identifying zoonotic virus infections in which standard defenses often fail, ultimately making dependence on standard technologies doomed, e.g., seen in the SARS outbreak in the past decade. Our unique work has allowed us to discover new nonhuman primate alphaherpesviruses in langurs, mangabeys, baboon, and patas monkeys and has led to the identification of a potentially effective drug for treatment of late-stage B virus zoonosis. Our laboratory, in its clinical capacity, serves as the home of the National B Virus Resource Center, which provides global diagnostic support for detection of B virus zoonotic disease as well as for maintenance of specific pathogen-free macaque colonies in support of NIH’s SPF HIV/AIDS Animals Models, which enables active collaborations with a wide number of commercial, academic, nonprofit research laboratories, zoos, and wild-life preserves. This part of our laboratory provides 24/7/365 emergency diagnostic testing performed by registered medical technologists who are dedicated to providing state-of-the art, high-throughput diagnostics for viruses requiring BSL-3 and BSL-4 containment. The Viral Immunology Center is home of the only BSL4 laboratory on the campus of a public university that trains both undergraduate and graduate students to be the future leaders in studies of special pathogens requiring the highest levels of biocontainment.