4501A Thomas Hall
919.515.2391 (dept office)
Jennifer C. Miller
Borrelia Burgdorferi pathogen-host interactions
Jennifer C. Miller was born in Lexington, KY, but spent her formative years in White Plains, MD (a smaller entity, but still part of the burgeoning Washington D.C. suburbs). As an undergraduate biology major at James Madison University in Harrisonburg, VA, she became fascinated by the inherent tug of war between infectious microorganisms and the human immune system. As the daughter of a primary care physician, this curiosity initially led to a desire to attend medical school. Jennifer was well on her way to conquering JMU’s pre-med curriculum until she enrolled in a microbiology course that changed the course of her professional development. Bacteriology piqued her interest, and undergraduate research on compost-dwelling bacteria nurtured a love for benchwork and independent study. Now hooked, Jennifer received her B.S. in biology in 1997 and decided to pursue a Ph.D. in microbiology, but not before life intervened. While at JMU, Jennifer had met and fallen in love with her future husband, Chris, who had recently accepted a job offer in Syracuse, NY. Jennifer agreed to move to Syracuse with Chris and postponed attending graduate school. While in Syracuse, Jennifer performed laboratory benchwork, first as an intern, then as a technician, for the Departments of Anethesiology and Surgery at the SUNY Health Science Center. It was here that she was first exposed to and gained experience in, the use of animal models in biomedical research. Jennifer’s work as a technician intensified her desire to obtain a Ph.D., and one year later, in the Summer of 1998, she enrolled in the University of Kentucky’s Ph.D. program in microbiology. She received her Ph.D. in 2003. Both Jennifer’s doctoral work and her first two years of post-doctoral training were conducted under the supervision of Dr. Brian Stevenson. This work focused on the characterization of Borrelia burgdorferi (the Lyme disease spirochete) lipoproteins and their contribution to mammalian infection. During the course of these studies, Jennifer became interested in B. burgdorferi ‘s interactions with the host’s immune system and desired to learn more about working with mouse models. This led to a post-doctoral fellowship in Dr. Janis Weis’ laboratory at the University of Utah, where Jennifer worked to elucidate mechanisms that regulate B. burgdorferi-induced arthritis development in inbred mice destined to develop severe arthritis. After almost 4 years in Utah, Jennifer wanted to return to the southeastern U.S. and eagerly relocated to North Carolina. She joined the Department of Microbiology at NCSU in September of 2009.
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted via the bite of hard ticks to humans and numerous other animals. The clinical characteristics of Lyme disease in humans are highly variable and difficult to diagnose, but can include a skin rash called erythema migrans, flu-like symptoms, neurological impairment, carditis and arthritis. Although curable with appropriate antibiotic therapy, 60% of untreated human patients develop a subacute arthritis in a large joint, such as a knee or elbow, and is associated with the presence of bacteria within joint tissue. The mechanisms underlying subacute Lyme arthritis development are largely unknown, but studies utilizing mouse models of Lyme arthritis have implicated both host genetics and innate immune responses in disease development. Further elucidation of the innate immune components involved in Lyme arthritis development and of the signal transduction pathways utilized by these effector molecules will contribute to the development of improved theraupeutic agents for Lyme arthritis patients. In addition, knowledge obtained from studying Lyme arthritis, which has a defined trigger because it is caused by B. burgdorferi infection, can be applied to other forms of debilitating arthritis for which defined triggers have not been identified, such as Rheumatoid arthritis.
My research focuses on the interaction between Borrelia burgdorferi and the innate immune system. My laboratory utilizes tissue culture and mouse models to examine both the bacterial and host-derived mechanisms driving the induction of Lyme arthritis. While a post-doc, I uncovered a novel and previously unappreciated role for Type I Interferon (IFN) in the development of severe Lyme arthritis within genetically susceptible inbred C3H mice by demonstrating that blockage of the Type I IFN receptor (IFNAR1) prior to B. burgdorferi-infection prevented the development of severe arthritis within the rear ankle joints of these mice. I also demonstrated that induction of IFN-profile genes did not depend upon B and T cell infiltration into joint tissue, as these genes were transcribed within the joints of infected C3H scid mice at levels equivalent to those seen in wild-type C3H mice. These data indicated that cells of the innate immune system govern induction of IFN-responsive gene transcripts within infected joint tissue.
Utilizing murine bone marrow derived macrophages (BMDMs) as a model cell type, I discovered that B. burgdorferi-mediated induction of Type I IFN-responsive transcripts by these cells does not require TLRs 2,4, 9 or the adapter molecule MyD88.
My laboratory is currently focused on the identification of B. burgdorferi ligands that trigger IFN-profile induction in macrophages, and the continued elucidation of innate immune components, and mechanistic pathways that drive both Type I IFN production and the development of Lyme arthritis. These studies will provide further insight into the mechanisms driving Lyme arthritis development, and lead to the development of improved theraupeutic interventions for Lyme disease patients.