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Infections, Inflammation and Pain

Developing new agents and interventions to improve outcomes and quality of life for patients with chronic pelvic pain and benign urologic conditions.

 David Klumpp Lab

Molecular Mechanisms Of Bladder Inflammation and Pelvic Pain

Research Description

Our laboratory employs state-of-the-art cell culture and animal models to pursue multi-disciplinary projects in bacterial pathogenesis and neuro-immune interactions in a crippling pain syndrome.  A key to our success is the rich training environment resulting from the close collaboration between clinical and basic scientists.

Urinary tract infection (UTI) is both a major medical issue and a fascinating problem of bacterial pathogenesis.  We investigate all aspects of host pathogen interactions, from the immediate biochemical signaling evoked in bladder cells, to the associated inflammation, to the development of adaptive immune responses.  We recently identified a novel signaling response of bladder cells induced by binding of uropathogenic E. coli (UPEC) that mediates the mutually exclusive processes of epithelial cell apoptosis and bacterial invasion of bladder epithelial cells; how this occurs is an active area of study.  We have also identified a candidate live-attenuated UTI vaccine based on a UPEC mutant.  We find that the UPEC mutant vaccine induces protective responses 100-fold greater than wild type UPEC.  We are now determining the mechanism of this enhanced response by testing the hypothesis that the UPEC mutant skews the normal immune response and thus generates a more effective immunity.

Although pelvic pain can result from acute infection, interstitial cystitis (IC) is a debilitating chronic pelvic pain syndrome of unknown origin that is often considered a chronic bladder inflammation. We utilize a herpesvirus to induce an IC-like condition in mice  Using this model, we have identified the mechanisms that result in both bladder pathophysiology and pelvic pain. Interestingly, while both pain and bladder damage require mast cell activation, pelvic pain results from the release of mast cell histamine, whereas bladder pathology is driven by mast cell release of tumor necrosis alpha (TNF). Current studies include the genetic basis of pain susceptibility, the spinal regulation of histamine and TNF release and the viral basis of pain. In addition, we recently were awarded a prestigious NIH center grant to study pelvic pain syndromes. The center award will extend our bladder pelvic pain studies to prostate- and bowel-associated pelvic pain and determine the mechanisms of pelvic organ crosstalk and signal integration in the spinal cord in mice. Our center collaborators will examine cortical and cognitive changes in pelvic pain patients using a combination of functional MRI and behavioral tests and develop novel quality-of-life tests to characterize pelvic pain non-invasively within populations. Thus, this center will illuminate pelvic pain mechanisms in clinical, epidemiologic and basic animal studies.

For more information, visit Dr. Klumpp's faculty profile.


See Dr. Klumpp's publications in PubMed.


Dr. Klumpp

 Praveen Thumbikat Lab

Studying benign prostate diseases, chronic prostatitis/chronic pelvic pain syndrome

Research Description

The focus of research in the laboratory is to understand the pathogenesis of genitourinary diseases with emphasis on benign prostate disease in humans. Inflammation is a significant finding in a variety prostate diseases including prostatitis, BPH and prostate cancer. We study microbial and autoimmune mediated inflammation and innate and adaptive immune mechanisms in prostate disease. A particular area of interest is chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a debilitating medical condition characterized by dysuria and pain.  Projects in the lab use a combination of in vitro studies, animal models and clinical specimen assays to examine questions of interest such as the role of chemokines and T-cells in chronic pelvic pain.

For more information, see the faculty profile of Praveen Thumbikat, PhD.


View Dr. Thumbikat's publications at PubMed


Email Dr. Thumbikat

Phone 312-503-1050

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