Primary Faculty

Jimmy Ballard, PhD

Professor and Chairman

PI/Director, Oklahoma Center for Microbial Pathogenesis and Immunity, CoBRE


Research Interests:

The Ballard lab studies fundamental aspect for Clostridioides difficile physiology and mechanisms of pathogenesis.  C. difficile is a leading cause of hospital-acquired infections and routinely infects patients undergoing antibiotic treatments.   Though C. difficile is a strict anaerobe, disease is initiated through environmental exposure to inert spores that germinate once within the gastrointestinal tract.  After colonization, C. difficile produces bacterial toxins that further promote interations with the colonic epithelium, trigger inflammation, and damage cells.  As part of a longstanding project in our lab, we are studying the effects of C. difficile TcdB, a potent cytotoxin.  In a more recent project, we’ve studied a peptide-based regulatory system that appears to influence sporulation, motility, and toxin expression in C. difficile

C. difficile TcdB.  TcdB is a member of the large clostridial toxin family (LCT) that damage host cells by altering cell structure and cell survival.   LCTs transverse target cell membranes and enter the interior of the cell.  Once inside the targeted cell, LCTs glycosylate small GTPases, which are upstream regulators of transcription and cell structure.  To enter cells, TcdB binds to cell surface receptors and triggers endocytosis.  Following endosomal acidification, TcdB translocates into the cytosol of the cell where it hydrolyzes UDP-Glucose and transfers the liberated sugar moiety to Rho, Rac, and Cdc42.  This process of substrate glucosylation renders the targets inactive and causes cells to lose critical functions needed for survival.  Of particular interest to our group over the past decade is the fact that particular strains of C. difficile produce variant forms of TcdB.  We have termed the two major forms as TcdB1 and TcdB2.   The toxins differ in the receptor-binding profiles, efficiency of autoprocessing, rates of cell entry, and overall antigenicity. We are currently funded by the NIH to elucidate how these differences in TcdB1 and TcdB2 ultimately affect the outcome of disease.  We use a variety of genetic approaches to engineer strains of C. difficile and the recombinant toxins.  This is combined with cellular assay and in vivo infection models that allow us to probe the molecular details of TcdB1 and TcdB2 activities.

 

Autoinducing peptide based quorum sensing in C. difficile.   Similar to other gram-positive bacterial pathogens, C. difficile encodes an accessory gene regulator (Agr) system that produces an extracellular peptide used for density-dependent regulation of various activities.  In the prototypical Agr system, the autoinducing peptide is secreted from the cell and once it accumulates to a critical concentration the peptide interacts with a sensor histidine kinase to promote changes in gene expression via a response-regulator.   Interestingly, the Agr1 system in C. difficile contains the machinery for peptide expression and secretion but lacks a recognizable sensor kinase.  In a recent publication we showed that the Agr1 system influences sporulation and motility, as well as toxin expression. However, by using a combination of genetic approaches and mutants of C. difficile, we found that the Agr1 peptide may have intracellular activities not dependent on the peptide’s release from the cell.  This is a novel and previously undescribed aspect of an Agr system.  Studies are currently underway to determine how the intracellular peptide influences gene expression in C. difficile

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Darrin Akins, PhD

Professor, Associate Vice President for Health Sciences Research


Research Interests:

Pathogenic spirochetes, Lyme disease pathogenesis, host-parasite relationships.

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Kevin Brown, PhD

Assistant Professor


Research Interests:

Cellular and molecular biology of apicomplexan parasites. Areas of special interest include parasite motility, protein secretion, second messenger signaling, genetics, and pathogenesis.

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Michelle C. Callegan, PhD

George Lynn Cross Research Professor


Research Interests:

Molecular Pathogenesis of Bacterial Ocular Infections

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Daniel J.J. Carr, PhD

George Lynn Cross Research Professor


Research Interests:

Neuroimmunology; Mucosal Immunology with an emphasis on the eye; herpes simplex virus type 1-induced lymphangiogenesis and encephalitis, vaccine development

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Maureen Cox, PhD

Assistant Professor


Research Interests:

The intersection of the immune and nervous systems during infection and tumorigenesis.

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Madeleine W. Cunningham, PhD

George Lynn Cross Research Professor


Research Interests:

Molecular mimicry, Autoimmunity and Infection 

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Zachary Dalebroux, PhD

Assistant Professor


Research Interests:

Bacterial pathogenesis, innate immunity, antimicrobial resistance, membrane lipid remodeling, biochemistry of transmembrane proteins, bacterial glycerophospholipids.

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David Dyer, PhD

Professor


Research Interests:

Microbial genomics, bacterial iron transport, bacterial regulatory networks, microbial pathogenesis

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Kevin Fuller, PhD

Assistant Professor


Research Interests:

Fungal pathogenesis, fungal genetics, signal transduction, antifungal therapy

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Lori Garman, PhD

Assistant Professor, Graduate Student Liaison In-Training

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William Hildebrand, PhD

George Lynn Cross Research Professor


Research Interests:

The major histocompatibility complex (MHC) class I and class II molecules.

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Molly Hill, PhD

Professor, Graduate Student Liaison

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Mark Lang, PhD

Professor, Presbyterian Health Foundation Presidential Professor


Research Interests:

NKT cells and regulation of humoral immune responses

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Rodney Tweten, PhD

George Lynn Cross Research Professor


Research Interests:

Structural biology and biochemistry of bacterial protein toxins

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Lauren Zenewicz, PhD

Assistant Professor


Research Interests:

Inflammation, mucosal immunology, cytokines

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