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MAPP (Multidisciplinary Approach to Pelvic Pain Research Network)

The UI Department of Urology is proud to have been selected as one of only six sites in the nation for this groundbreaking five-year study of the etiology and natural history of urological chronic pelvic pain syndromes (UCPPS). Dr. Karl Kreder, Professor and Head of the UI Department of Urology, serves as Site Director, overseeing the four inter-related studies here at the UI, and coordinating these investigations with off-site researchers in the MAPP network.

As with many chronic pain disorders, UCPPS are poorly understood and characterized, and treatment is mostly empirical and unsatisfactory. The findings from this epidemiological study will provide insight into whether the various UCPPS syndromes in men and women represent a single heterogeneous diagnostic entity, or several separate problems. In addition, this Trans-MAPP EP Study will provide insights about whether psychosocial variables play a significant role in symptom persistence, resolution, or exacerbation, as well as healthcare utilization and whether UCPPS patients can be sub-grouped based on longitudinal symptom patterns. Finally, the careful and comprehensive phenotyping battery used in this study will serve as the core assessment for all participants in MAPP-related studies, including those examining biomarkers, infectious agents, brain imaging and other clinical hypotheses.

Dr. Yi Luo is currently working to establish a cystitis model with concomitant bowel inflammation, to determine the potential impact of bowel inflammation on local cystitis. Because a high prevalence of irritable bowel syndrome (IBS) has been observed in patients with chronic pelvic pain syndromes, this work is aimed at establishing a murine model to examine the inflammatory and gene expression profiles for localized cystitis and cystitis with IBS, and to explore possible responses to intravesical agents.

Dr. Michael O’Donnell is seeking to characterize the chemokine repertoire of the urothelium, identify patterns of aberrant chemokine/cytokine expression in patients with IC and develop a transgenic murine model of cystitis susceptibility by bladder-specific overexpression of MCP-1. Given the significant role of MCP-1 in other chronic human inflammatory diseases, it is likely that it also plays a central role on at least some forms of inflammatory cystitis. Completion of this study could lead to the opportunity to test treatment strategies for forms of cystitis that manifest aberrancies in chemokine expression.

Dr. Susan Lutgendorf’s project focuses on the role of the neuroendocrine stress response in the pathophysiology of cystitis and the related chronic pain syndromes of IBS and fibromyalgia. Her studies include the examination of levels of HPA activity and glucocorticoid receptor sensitivity, the relationships between HPA activity, inflammatory mediators and symptoms at baseline, as well as the relationships between early childhood adversity, current life stress and HPA dysfunction and inflammatory biomarkers.

Dr. Catherine Bradley is pursuing studies to estimate cross-sectional prevalences and evaluate associations among baseline characteristics of subjects with UCPPS, including interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis (CP). She is also investigating long-term profiles of symptoms, fluctuation of symptoms, risk factors for worsening of symptoms, and impact of symptoms on healthcare seeking and quality of life.

Immunotherapy Studies

Dr. Yi Luo is investigating new immunotherapeutic strategies for urinary bladder cancer. His laboratory recently demonstrated that systemic administration of anti-IL-10 receptor 1 (anti-IL-10R1) mAb could enhance intravesical BCG induction of Th1 immune responses and anti-bladder cancer immunity in a preclinical animal model (PubMed). The combination therapy appeared to be more effective than BCG monotherapy in treating localized bladder cancer and preventing cancer metastasis to the lung. Currently, Dr. Luo’s lab is identifying the mechanisms underlying the enhanced effect of this combination therapy.

Dr. Lyse Norian’s investigations focus on using cellular and molecular techniques to explore the nature of tumor-derived dendritic cell and T cell functional deficiencies. Immunotherapy is a promising approach for the treatment of advanced solid tumors, but progress in this area is impeded by the fact that growing tumors suppress protective immunity in a variety of ways. Dr. Norian’s laboratory uses cellular and molecular techniques to explore the nature of tumor-derived dendritic cell (DC) and T cell functional deficiencies. Long-term goals are to develop novel, immune-based therapies for advanced solid tumors, using the knowledge gained from pre-clinical studies. Since the goal is to ultimately apply laboratory findings to the clinical setting, Dr. Norian’s team is also interested in understanding how co-morbidities such as obesity impact protective immune responses in the presence and absence of tumor growth. They recently found that obesity impairs protective anti-tumor immune responses, and are now identifying the mechanistic basis for this failure.

Basic research in Dr. Norian’s laboratory is performed in a variety of murine models, and her team is now translating these findings into studies on samples from cancer patients. Murine tumor models routinely used include metastatic renal cell carcinoma (Renca), localized and metastatic prostate cancer (RM-11), spontaneous breast cancer (NeuT), metastatic breast cancer (4T1), and localized fibrosarcoma (CMS5). The use of multiple models helps to substantiate findings across tumor models, to determine if findings are specific to one type of cancer, or are broadly applicable.