Professor, Director Paul G. Allen School for Global Animal Health
Room: Allen Center 101
General Research / Expertise
Our lab studies mechanisms by which zoonotic intracellular bacterial pathogens survive and thrive within host cells. We are specifically interested in understanding how these pathogens manipulate host cells to establish a hospitable environment that supports bacterial growth. Addressing these questions requires that we work with and understand many approaches and disciplines including microbial genetics, immunology cell biology and physiology.
We are also currently working to develop alternatives to antibiotics for treating bacterial infections. Specifically we are studying small molecules that inhibit intracellular pathogen growth by enhancing innate host antimicrobial responses, as well as molecules that inhibit host cell processes that transiently support bacterial intracellular growth. Pathogens are far less likely to develop resistance to such treatments. Also, treatments such as these target specific pathogens without impacting healthy microorganisms.
Results from our research lead us to clearer understanding of how bacteria cause disease. By definition successful pathogens somehow inhibit or overcome host immune responses. Therefore our research also informs us about successful and unsuccessful host immunity mechanisms. Knowledge of both of these processes, immune mechanisms and pathogen resistance mechanisms, is critical to developing successful treatment and vaccination strategies.
We work primarily with Francisella tularensis to examine intracellular pathogen virulence and pathogenesis strategies. F. tularensis naturally infects over 300 animal species and is one of the most virulent zoonotic pathogens known. Exposure to as few as 10 bacterial cells is sufficient to initiate lethal disease in humans. Exposure to 1 bacterial cell is sufficient to kill a mouse. In other words F. tularensis is an exceptionally talented pathogen. Upon initial transmission to a new host F. tularensis suppresses host innate immune responses that typically alert the host to pathogen exposure. The bacteria therefore essentially go undetected. The bacteria are taken up by macrophages where they rapidly replicate and within 24 hours inhabit nearly 70% of the macrophage cytoplasm. Bacterial interactions with the infected cell that drive this rapid intracellular growth is a significant research interest of our lab.
Interestingly, infected macrophages do not exhibit any signs of infection or distress. Thus the infected cells still appear to function essentially normally. In fact, we have observed that F. tularensis infected macrophages continue to be mobile and will travel through space, contact and deposit bacteria into previously uninfected cells. This observation demonstrates that this bacterial pathogen can be transmitted directly from cell to cell without becoming exposed to extracellular space where it could be susceptible to humoral immune responses. We recently found that this cell to cell transmission process is a host drive mechanism that is exploited by F. tularensis as well as other intracellular bacterial pathogens. We are currently studying this phenomenon that is related to, but distinct from, trogocytosis (cell nibbling), with the goal of understanding the mechanism of this process and how it contributes to pathogen growth and dissemination, as well as how it may be exploited to enhance the development of effective host immune responses to infection.
Dr. Kawula is an infectious disease microbiologist with research programs focusing on how intracellular bacterial pathogens evade host defenses and survive and thrive in hostile animal host environments. He started out majoring in Forestry at the University of Idaho, but switched to Bacteriology and Biochemistry after becoming fascinated with microbes in a sophomore microbiology course taught by the late Al Lingg. After obtaining a BS in Bacteriology in 1980 he completed a MS degree in 1982 at the University of Idaho where he was the first person to develop methodologies for genetically manipulating a fungus that was used to combat pea leaf weevil infestations. Tom married the day before defending his Masters Thesis, and the following week he and his wife Carol moved across the country to Chapel Hill, NC where he entered the Microbiology and Immunology doctoral program at the University of North Carolina. His doctoral research focused on how Neisseria meningitides (the bacteria that causes rapidly progressing fatal meningitis) evades detection by the host immune system.
After obtaining his Ph.D. Dr. Kawula continued his scientific training in genetics and molecular biology at North Carolina State University. He assumed his first faculty position at Cornell University, College of Veterinary Medicine. He and his growing family returned to the University of North Carolina in 1992 where he expanded his infectious disease research program and became deeply involved in interdisciplinary graduate training and in educating medical students. While at UNC Dr. Kawula served as director of the Microbiology and Immunology graduate program which averaged over 50 doctoral students per year, he was appointed to the Graduate School Board Advisory Board, and for 3 years he served as one of the founding Directors of a privately funded, institution wide interdisciplinary doctoral student society. After 24 years at UNC Washington State University presented Dr. Kawula with the opportunity to lead the Paul G. Allen School for Global Animal Health. The opportunities and challenges of this position encompassed everything that Dr. Kawula cherishes; building and supporting interdisciplinary international training programs, mentoring young scientists, conducting infectious disease research, and getting to do all of these activities at a world class institution.
I can’t claim to be one of those people who found a career calling early in life. Honestly I did whatever I could to avoid science classes in high school. I took the bare minimum to graduate while stacking my schedule with every literature and writing course I could find. But I did love the outdoors, specifically hiking and fishing, and I had some vague romantic notion of being a Park Ranger so I entered the University of Idaho as Forestry major. It was a good course of study with a balance of social and hard science classes. Surprisingly to me I thrived in the science classes so I started loading my electives with advanced biology courses. When we started covering infectious diseases in an introduction to microbiology course I was sold, and switched my major to Bacteriology and Biochemistry. When I graduated, which was the same year that Mt. St. Helens blew her top, very little was known about how bacteria or virus’s caused disease. At the same time recombinant DNA technologies were just being discovered and a new field of study was emerging where molecular biology approaches were applied to understanding both disease and host immune mechanisms. This truly was revolutionary, and I wanted to be a part of it. The University of North Carolina – Chapel Hill was one of the few institutions in the country where this type of research was taking place, another was the University of Washington. I just couldn’t bring myself to be a Husky so I headed southeast for my Ph.D. dissertation research. I have remained involved in infectious disease research for my 30 plus year career and it is as challenging and rewarding now as it was when I first started. Much of what I love about my research is how it allowed me to be engaged in training scientists at all levels, from undergrads to junior faculty.
Away from work I enjoy hiking, biking, and skiing with my wife Carol.
Education, Training and Awards
Postdoctoral Fellow, Microbiology, North Carolina State University (1987-1990)
Ph.D., Microbiology and Immunology, University of North Carolina, Chapel Hill, NC (1987)
M.S., Bacteriology and Biochemistry, University of Idaho, Moscow, ID (1982)
B.S., Bacteriology, University of Idaho, Moscow, ID (1980)
Deans Faculty Leadership Initiative (2009)
Departmental Award for Teaching Excellence (2001)
John E. Fogarty Senior International Fellowship Award (2000)
Kenan Faculty Research Scholar (2000)
Director (2012 – 2016), Research Experiences for Undergraduates (REU) Site: NSF-funded Summer Undergraduate Research Experience in Molecular Biosciences, University of North Carolina, Chapel Hill, NC
Professor (2010 – 2016), Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC
Director, University Fellows/Royster Society of Fellows (2006 – 2009), The Graduate School, University of North Carolina, Chapel Hill, NC