Molecular Mechanism and Biomarkers of Interstitial Cystitis (IC)
One of the major focus areas in the J. Kim Laboratory is the study of the molecular signature for the diagnosis of IC. The goal of our IC studies is to identify and validate sensitive and noninvasive diagnostic biomarkers using urine specimens that stratify IC patients from healthy subjects.
IC is a debilitating condition that presents with a constellation of symptoms including bladder pain, urinary urgency, frequency, nocturia and small voided volumes in the absence of other identifiable etiologies. Approximately 3 to 8 million women (up to 7 percent of women in the US) are diagnosed annually as IC, and over 80 percent of IC patients are women. There is no gold standard for IC diagnosis, and in general, it takes approximately four to five years from the first office visit to obtain a definitive diagnosis of IC. Thus, differentiating IC from other conditions is still a diagnostic challenge, and objective diagnostic markers are urgently needed to improve prospects for clinical care. Recently, we have obtained evidence that levels of specific metabolites are perturbed in urine specimens from IC patients.
Cisplatin Resistance of Muscle Invasive Bladder Cancer
The incidence of bladder cancer recurrence following chemotherapy is high, thus the poor survival rate. Therefore, bladder cancer biomarkers that could predict a patient response to chemotherapy and probable disease course would allow better treatment strategies for individual patients. The goal of our bladder cancer study is to develop such predictive markers of bladder cancer that identify patients who are poor chemotherapy candidates, as well as to identify potential mechanism for re-sensitizing nonresponsive bladder cancers to chemotherapy.
Cholesterol Metabolism in Urological Diseases
Although the public health burden is considerable, the etiology of benign prostatic diseases, such as benign prostatic hyperplasia (BPH), is poorly understood. Prostate health is highly controlled by genome and individual lifestyle. The cholesterol-enriched Western diet may be a risk factor for prostate health. Recent epidemiologic studies have suggested that cholesterol-lowering drugs (e.g., 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors) may lower prostate cancer progression; however, very limited studies have been performed on benign prostate diseases.
In a previous J. Kim Laboratory study, a global gene expression profile, using a novel method of raising and lowering circulating cholesterol in mice, has suggested that cholesterol can mediate reactive changes in the prostate, promoting disease. The functional analysis has revealed the molecular mechanism by which the normal prostate in situ, and prostatic epithelial cells in culture, sense and respond to the altered cholesterol levels. We also suggested that ATF3, an early responsive gene and a transcription factor, is a modulator of cholesterol response in prostate cells, thus triggering biological effects. Since several cholesterol-targeting agents (e.g., ezetimibe) are clinically available, the results from this study are of direct relevance to human prostate health, and the cholesterol-lowing drugs may be a tremendous health benefit, in particular, to prostate health.
Studies in the J. Kim Laboratory are supported by several active grants sponsored by the National Institutes of Health (e.g., NIDDK and NCI), the Spielberg Prostate Cancer Discovery Fund and the Interstitial Cystitis Association Research Fund. J. Kim is a former American Urologic Association Foundation Scholar (now Urology Care Foundation), Edwin Beer Scholar (New York Academy of Medicine), Eleanor and Miles Shore Scholar (Harvard Medical School) and the “Imagine No IC” Research Scholar (Interstitial Cystitis Association Research Foundation).