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Kanchan Chitaley, PhD
and Hunter Wessells, MD
>> Kanchan
Chitaley bio
>> Hunter Wessells bio
Lab Members:
Lab Members (from left): Karen Engel, Hunter Wessells, Kanchan Chitaley, Ian Luttrell, Don Huynh, Stephen King
Karen Engel-- Research Technician
Don Huynh-- Research Scientist
Stephen King-- Urology Resident
Ian Luttrell-- Research Scientist
Diabetes-associated Erectile Dysfunction:
Vasculogenic Mechanisms
Research Interests Overall Goals:
Through basic science, epidemiological and clinical research, we aim to elucidate the mechanism(s) of vascular disease including penile vascular disease and the resultant erectile dysfunction (ED) associated with diabetes and general vascular inflammation associated with chronic air pollution exposure. Our ultimate goal is to identify potential new therapeutic avenues to restore vascular health. Our "bench to bedside" approach includes the use of a wide range of molecular, physiologic and epidemiological tools, as well as focused, local clinical studies.
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Active Basic Science Projects:
ED Related
- The role of elastin in veno-occlusive function and type II diabetic-ED
R01 NIH Pending (PI: Chitaley)
The outer layer of the corpus cavernosum, the tunica albuginea, is rich in elastic fibers and has the capacity to expand in response to the force of blood pressure, resulting in an increased length and diameter of the penis. However, the expandability of the tunica is finite, and ultimately the initial rise in intracavernosal pressure (ICP) along with the opposing force of the tunica albuginea activates a mechanical occlusion or “sandwiching” of the venous outflow. Thus, the combined inflow of blood following penile arteriole and sinusoidal dilation, as well as subsequent veno-occlusion, result in maintained elevation of ICP and erection. We recently found that db/db mice, a common mouse model of type II diabetes, have a veno-occlusive disorder that stems from a lack of tissue filling due, in part, to altered vasoreactivity consistent with impaired cavernosal relaxant ability. We also showed that these mice have may impairment in tissue distensability resulting from altered deposition of fibrillar collagen and elastin. Elastic fibers are assembled extracellularly and are comprised of elastin and specific microfibrillar proteins. In this project, we hypothesize that elastin deposition and fiber formation is critical for proper erectile function and that this process is altered in type II diabetic mice, resulting in impaired veno-occlusive function and erectile dysfunction. As elastin degradation is also known to occur in tissue following smoking and/or aging, this knowledge gained from this proposal may also have implications for erectile dysfunction associated with these risk factors as well. - Ceruloplasmin and Diabetic Vascular Endothelial Dysfunction R21 NIH
(PI: Chitaley)
Through microarray analysis, we found that ceruloplasmin (Cp), the predominant carrier of copper in the plasma, is up-regulated approximately 3-fold in the penile tissue from diabetic vs non-diabetic rats. Preliminary evidence suggests that the expression of Cp is similarly increased in the penile tissue in diabetic humans as well. Cp is reported to decrease the bioavailability of the potent vasodilator, nitric oxide, through various mechanisms. We are currently using the Cp-deficient (Cp-/-) mouse to determine the effect of the absence of Cp on penile vasodilation and erectile function. In addition, we are performing studies to examine whether the loss of Cp in these mice protects them from the development of erectile dysfunction following diabetic challenge. - Adiponectin and Type II Diabetes-Associated Erectile Dysfunction
R21 NIH (PI: Chitaley)
Adiponectin, an adipose-produced cytokine, is important for insulin sensitization, and is decreased in type II diabetic patients. Recent studies demonstrate that adiponectin has a vasoprotective role, primarily through direct endothelial and smooth muscle cell signaling. The general hypothesis of this study is that decreased adiponectin in type II diabetes contributes to poor penile vascular function and ED through the loss of nitric oxide-mediated function and vascular cell homeostasis.
General Vascular Disease
- Vascular Reactivity Following Chronic Air Pollution Exposure PO NIH
(PI: Kauffman; Project 3 PI: Chitaley)
Air pollution exposures are associated with cardiovascular disease, especially atherosclerotic disease such as myocardial infarction. Increasing evidence indicates that the major source of variation in air pollution's cardiovascular health effects is from exposure to traffic. The studies in our recently funded DISCOVER Center involve human, basic animal and epidemiologic evaluation. Specifically, our project (Project 3 of the Center) is in collaboration with Francis Kim (University of Washington) and Stephan VanEeeden (University of British Columbia) and involves examining mechanisms underling systemic and vascular inflammation following diesel exhaust exposure in mice.
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Active Clinical Research:
- Urological Complications of Diabetes – URO-EDIC
(PI: Wessells)
Type 1 diabetes has long been known to be associated with ED, but the role of glucose control and other complications such as nerve damage and microvascular disease remains unclear in human subjects. Through a unique collaboration with experts in diabetes research funded by the NIH, we are studying risk factors and the role of better glucose control on the development of ED. This ancillary study is part of EDIC, the Epidemiology of Diabetes Intervention and Complications Study. Men in EDIC have been followed for close to 17 years to determine the effect of intensive glucose control on complications of diabetes. URO-EDIC allows us to determine the risk and protective factors involved in the genesis of diabetes associated ED.
Active Clinical Trials
Prospective, Randomized, Controlled, Multicenter Trail of the Memokath 044TW Thermo-Expandable Stent for Maintaining Urethral Patency in Patients after Dilation of Internal Urethrotomy of Recurrent Stricture of the Bulbar Urethra
PI: Hunter Wessells, MD
Type: MVU20020001U, Engineers and Doctors, Inc. 1/1/05-12/30/07
The purpose of the study is to determine whether a novel stent is more effective than control in preventing stricture recurrence after internal urethrotomy.
Detection of Bladder Cancer by Microsatellite Analysis of Urinary Sediment: Multi-Institutional Study
PI: Hunter Wessells, MD
Type: MSA STUDY, Johns Hopkins University 9/1/06-8/31/07
The purpose of the study is to determine whether MSA can detect incident or recurrent superficial bladder cancer.
>> See other clinical trials.
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Current and Past Funding
Current Funding:
- Cardiovascular Disease and Traffic-Related Air Pollution: DISCOVER Center
PO NIH/NIEHS- Chitaley (PI Project 3) 6/08-5/13 - Disorganziation of Elastin Matrix Mediates Erectile Dysfunction
R01 NIH/NIDDK- Chitaley (PI) PENDING Anticipated 11/08-10/13 - Ceruloplasmin Mediated Penile Endothelial Dysfunction in Type I Diabetes
R21 NIH/NIDDK- Chitaley (PI) 7/07-6/09 - Erectile Dysfunction in Type II Diabetes: Role of Adiponectin
R21 NIH/NIDDK- Chitaley (PI) 1/06-2/09
Past Funding:
- Gene Therapy for Diabetic Penile Endothelial Dysfunction
RO1 NIH/NIDDK- Wessells (PI) 10/00-5/06 - Neural Melanocortin Signaling and Erectile Function
R21 NIH/NIDDK- Wessells (PI) 2/04-1/06 - Immortalized Human Cavernosal Endothelial Cells
R21 NIH/NIDDK- Wessells (PI) 9/04-8/06
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