Research Specialty: Bacterial pathogenesis focusing on Chlamydia

The pathogen we study
Chlamydia spp. are Gram negative, obligate intracellular bacterial pathogens which cause disease in humans as well as economically important domestic animals. These bacteria mainly infect the mucosal epithelial layer lining the lung, ocular, digestive, and genital tracts eliciting damage primarily in the form of immunopathology. In humans, C. trachomatis is responsible for trachoma (the leading cause of preventable infectious blindness worldwide, WHO) and is the leading cause of reported bacterial sexually transmitted infections (STIs) in the United States (and worldwide) with over 1.6 million chlamydia cases reported in 2021 (CDC). Infections in women are of particular concern as they can lead to pelvic inflammatory disease, life-threatening ectopic pregnancy, or infertility. Chlamydia pneumoniae infects the respiratory tract causing pneumonia. While the incidence of chlamydial pneumonia is unknown, there are over 2 million reported cases of pneumonia in the United States each year (CDC). Furthermore, C. pneumoniae infections are a suspected risk factor for the development of cardiovascular disease and other chronic conditions. While antibiotics are relatively effective in treating chlamydial infections, treatment failure occurs and the current antibiotics of choice are broad spectrum leading to disruption of the normal microflora  of the patient. Development of narrow spectrum, Chlamydia-specific antibiotics would be a boon to public health. Concurrently, the high percentage of asymptomatic chlamydia infections (≥60%), and the link between these infections and chronic disease, illustrates the urgent need to develop vaccines and anti-infectives. And, of course, we need continued public outreach for prevention of all STIs.

Research Interests

Overview
My lab is broadly interested in how bacterial physiology and metabolism, acting as atypical virulence factors, contribute to pathogenesis. We use Chlamydia as a model system for our studies. These bacteria transition between two distinct developmental forms: the environmentally stable infectious form known as the elementary body (EB) and the intracellular replicative form known as the reticulate body (RB). For successful infection, the EB must bind to a eukaryotic cell and become internalized, transform into an RB, modify host-vesicular trafficking pathways to obtain nutrients and avoid destruction by innate and adaptive immune responses, replicate before transitioning back into an EB, and finally exit from the host cell. Despite the essentiality of the developmental cycle to infection, the mechanisms regulating and "mechanics" responsible for differentiation remain largely undefined. In addition, we have a limited understanding of how these bacteria survive stress imposed by the host immune response. To address these gaps in our knowledge, we study how protein phosphorylation, metabolism, and chaperones and proteases contribute to chlamydial growth, development, and stress responses. Understanding these processes will facilitate development of new methods to prevent and treat chlamydial infections, ideally through chlamydial specific approaches that avoid causing dysbiosis of the microbiome. Furthermore, variations of the systems we study in Chlamydia are also found in other important bacterial pathogens. I am also deeply committed to the training and mentoring of undergraduate and graduate students, which I find to be one of the most rewarding aspects of my profession.

Ongoing projects
Elucidating the function and regulation of the chlamydial protein kinases (Pkn1, PknD, and Pkn5) and phosphatase (CppA) during bacterial growth.

Exploring the role of the chlamydial partner switching mechanism in regulating chlamydial development and metabolism.

Developing small molecule inhibitors targeting the chlamydial kinases and phosphatases (in collaboration with the Plunkett lab).

Querying the role of the cytoplasmic and periplasmic proteases in chlamydial growth and development and identifying small molecule inhibitors/activators for select chlamydial proteases. These projects are collaborations with the Ouellette and Conda-Sheridan labs at UNMC.

Side projects
We continue tinkering with genetic approaches to expand the growing chlamydial molecular tool kit.

Non-Chlamydia projects:
We work with the Choudhary and Kohli labs at SIUC to develop edible, antimicrobial nanocoatings for fruit and vegetables.

Teaching

Courses Taught within Microbiology Undergraduate Degree Program
2012-present   Instructor, Biochemistry and Physiology of Microorganisms (MICR425, Fall)
2012-2019        Co-Instructor (33%), Molecular Biology of Microorganisms Laboratory (MICR480, Fall)
2013-2016        Instructor, Introduction to Molecular Biology (MICR302, Spring)
2017-present    Instructor, Medical Microbiology (MICR403, Spring)
2024-present    Instructor, Microbiology Junior-Senior Seminar (MICR495, Spring)
Undergraduate Research Participation (MICR490)

Molecular Biology, Microbiology and Biochemistry Graduate Program (PhD and MS)
2019-2020         Seminar and Professional Training (MBMB 597, Co-Instructor)