2012 - 2013 Research Scholars
Thomas Chi, MD
2012 Joseph Segura, MD Scholarship in Endourology and Stone Management
Project Title: "Drosophila Melanogaster as a Novel, Genetically-Based Model of Urinary Stone Disease"
Institution: University of California, San Francisco
Mentor: Marshall Stoller, MD
Sponsor: Boston Scientific Corporation, The Endourological Society, and the "Friends of Joe."
Symptomatic kidney stones can be a significant source of severe pain, infection, and morbidity, affecting up to 12% of Americans and generating more than $2 billion in healthcare costs annually. Despite multiple studies extending over many years, the process of kidney stone formation remains poorly understood. One consequence of this lack of insight has been the limited progress made in developing medical or dietary interventions that prevent the occurance or recurrance of stones. Though several animal models have been developed for these purposes, all have significant limitations, as they mostly depend on non-physiological chemical treatments to induce stone formation. Dr. Chi's research will employ the fruit fly (Drosophila melanogaster) as an animal model because the species develops stones. Dr. Chi's laboratory work has shown that the stones from these flies contain hydroxyapatite, the primary component of early human stones.
Dr. Chi has also identified multiple gene knockdowns that suppress the formation of stones in the Drosophila model system. Given the similarities in tubule physiology between Drosophila and humans and the availability of powerful genetic tools in the fly, the fruit fly is an ideal system for examining the molecular basis of early stone formation. Dr. Chi's research hypothesizes that Drosophila melanogaster can be a meaningful model to improve understanding the initiation of kidney stone disease and to identify novel therapeutics.
Dr. Chi's Research Scholar Award is sponsored by Boston Scientific Corporation, The Endourological Society, and "Friends of Joe."
Christopher Long, MD
Project Title: "Calcineurin and NFAT Modulate ctaf Following Partial Bladder Outlet Obstruction and Offer Potential Therapeutic Targets"
Institution: Children's Hospital of Philadelphia
Mentor: Stephen Zderic, MD
Sponsor: AUA Mid-Atlantic Section Research Scholar Endowment Fund
Bladder wall hypertyophy may develop in patients with either anatomic bladder outlet obstruction (such as benign prostatic hypertrophy in adult men or posterior urethral valves in the male fetus or neonate), or in patients with neurogenic bladders (due to spina bifida or following spinal cord injury). Up to 30% of patients will have persisting complaints of lower urinary tract symptoms despite sucessful surgical correction of the anatomical obstruction. Thickening of a person's bladder can occur in response to stress, or to resistance or blockage of urinary flow. When this occurs, increased pressure within the bladder, which is the storage unit of the urinary system, can result in damage to the kidney. The wall of the bladder is composed of muscle, and it is enlargement of this muscle that ultimately results in thickening of the bladder wall. Dr. Long's research will look at components of this mechanism, specifically the interaction of calcium and the muscle itself. His research goal is to develop a compound that can be placed within the bladder, which will block or slow the process of bladder thickening.
Ferenc Rick, MD PhD
Project Title: "Investigation of Effects of Antagonist of Bombesin/gastrin-releasing Peptide (BN/GRP) and its Combination with Antagonists of GHRH or LHRH on Experimental Benign Prostatic Hyperplasia"
Institution: University of Miami Miller School of Medicine
Mentors: Andrew Schally, PhD & Norman Block, MD
Sponsor: AUA Southeastern Section Research Scholar Endowment Fund
Benign prostatic hyperplasia (BPH), is a common, age-related condition, characterized by prostate enlargement and bothersome lower urinary tract symptoms. The disease affects over 75% of men above 50 years of age. Currently, there is no completely effective treatment for BPH. Despite the vast burden of BPH on public health, its pathogenesis remains undetermined. The need for novel treatments for BPH has prompted the study of unique features of prostate physiology with the goal of uncovering potentially new therapeutic targets. Dr. Rick's research will study neurohormones and neurohormone receptors present in the prostate, to elucidate a more complete understanding of the role of peptide growth factors in BPH development, ultimately to develop new therapeutic strategies for the treatment of BPH.
2012 - 2014 Research Scholars
Peter Chang, MD
Project Title: "Measuring Patient-Reported Prostate Cancer Outcomes at the Point of Care"
Institution: Beth Israel Deaconess Medical Center
Mentors: Martin Sanda, MD; Andrew Wagner, MD & Donna Berry, PhD, RN
Sponsor: Dornier MedTech
Quality of care is a complex entity that can be evaluated from the perspective of the provider and the patient. Examples of the patient perspective of care quality include health-related quality of life (HRQOL), anxiety, and regret. Patient-reported outcome (PRO) evaluation is the cornerstone of assessing care quality from the patient perspective, but its use in prostate cancer has predominantly been limited to the research realm, and their adoption in routine clinical care processes has lagged because validated instruments for measuring patient-reported outcomes are too onerous to enable real-time measurement at the point of care. Dr. Chang's research goal is to better enable the integration of PRO measures into the routine clinical care of prostate cancer patients by adapting validated PRO instruments for use at the point of care. The feasibility of Dr. Chang's work lies in the observation that as the increasing prevalence of digital devices may be expanding the clinical setting into the comfort of patients’ homes, the use of digital PRO instruments may widen PRO dissemination. Accomplishing the aims of this study would provide future recommendations to patients and physicians on how to optimize PRO instrument use in the routine clinical practice, with the overall goal of promoting patient-centered care and improving care quality.
Dr. Chang's Research Scholar Award is sponsored by Dornier MedTech.
Timothy Daskivich, MD
Project Title: "The Impact of Age and Comorbidity on Survival and Treatment Decision Making in Men with Early-Stage Prostate Cancer"
Institution: University of California, Los Angeles
Mentor: Mark Litwin, MD, MPH
Sponsor: AUA Western Section Research Scholar Endowment Fund
While early-stage prostate cancer is a common disease, tumors are often slow-growing and take a long time to cause symptoms or affect survival. Aggressive treatment of early-stage disease often causes side effects such as erectile dysfunction, urinary incontinence, and bowel dysfunction that can significantly affect quality of life. As a result, current treatment guidelines recommend that men with multiple major medical conditions who have a high risk of dying from other causes should not be treated aggressively for localized prostate cancer. However, because there is very little information on how other medical conditions and age relate to life expectancy, it is hard to counsel men for or against aggressive treatment. In fact, studies have shown that men with multiple major medical conditions are being overtreated with aggressive therapy despite a low likelihood of long-term benefit. Dr. Daskivich's research aims to study men insured by Medicare and United Health Care to determine the impact of age and comorbid conditions on long-term risk of death from other-causes, so that men can be better informed about their likelihood of benefit before committing to aggressive treatment. His research will also analyze how many men are being overtreated for early-stage disease based on their comorbid conditions, and then determine the medical and financial costs of overtreatment.
2012 Urology Care Foundation Research Scholar Funded by the Allergan Foundation
Nirmal Jayabalan, PhD
Project Title: "Functional Role of Organic Cation Transporters (OCTs) in Bladder Physiology and Pharmacology"
Institution: Oakland University William Beaumont School of Medicine
Mentors: Ananias Diokno, MD; Michael Chancellor, MD & Pradeep Tyagi, PhD
Sponsor: The Allergan Foundation
The urinary bladder is a unique organ in our body responsible for temporary storage of unwanted liquid waste (urine) prior to its voluntary exit from the body at a socially acceptable time. Dr. Jayabalan's research is aimed at determining how the bladder erects such a water tight barrier to push away the toxins and ions contained in urine and prevent them from mixing with blood perfusing through the organ. The human genome sequencing project has highlighted the role of specialized outward/inward-facing membrane proteins called transporters in establishing barrier function of cells, such as multidrug resistance proteins, multidrug resistance-associated proteins, and organic cation transporters. Dr. Jayabalan hypothesizes that uptake and efflux membrane transporters play a significant role in determining which drugs gain access into the bladder tissue from the urine. It is the goal of his research to identify key drug transporters in the urothelium and to use this information to gain an understanding of pharmacokinetic and pharmacodynamics of most widely used drugs to alter bladder function (anti-muscarinic drugs) using known transporter inhibitors.
Dr. Jayabalan's Research Scholar Award is sponsored by The Allergan Foundation.
2012 Urology Care Foundation Research Scholar Award Funded by the Allergan Foundation
Shankar Parajuli, PhD
Project Title: "Pharamacological Activation of Small and Intermediate Conductance Calcium Activated Potassium Channels: A Novel Approach to Control Urinary Bladder Smooth Muscle Function"
Institution: University of South Carolina
Mentor: Georgi Petkov, PhD
Sponsor: The Allergan Foundation
Dr. Parajuli’s research is associated with urinary bladder disorders such as overactive bladder (OAB) and urinary incontinence (UI). Structural and functional change in bladder function can damage the upper urinary tract, and these bladder impairments result in increased bladder contractility characterized by involuntary and frequent urination. The elderly population and especially women are frequently affected with these problems and, as a result, often experience social discomfort and embarrassment. A balance in bladder contraction and relaxation by which urine is expelled from the bladder and stored in the bladder respectively, is necessary for healthy urinary bladder functions. The cause of urinary disease is principally due to the alteration in urine storage and micturation mechanism. The physiological function of the urinary bladder is regulated by the opening and closing of ion channels existing in cell membrane, and a malfunction in this mechanism results in urinary diseases. Dr. Parajuli’s research proposes to study these channels and generate findings that will ultimately help to develop new pharmacological approaches for the treatment of urinary bladder disorders such as OAB and UI.
Dr. Parajuli's Research Scholar Award is sponsored by The Allergan Foundation.
Sargurunathan Subashchandrabose, PhD
Project Title: "The Identification of Genes Expressed in Uropathogenic Escherichia coli During Human Infection"
Institution: University of Michigan
Mentor: Harry Mobley, PhD
Sponsor: AUA North Central Section Research Scholar Endowment Fund
Bacterial infections of the urinary tract are major public health problems. In the United States alone, around 11 million cases of urinary tract infections occur annually. The majority of these infections are caused by a group of bacteria known as the uropathogenic Escherichia coli. These bacteria contain approximately 5,000 genes. Some of these gene products are required to cause urinary tract infections in humans, and Dr. Subashchandrabose's research is aimed at identifying these gene products. The research goal would be to enable the development of new treatment options for urinary tract infections.
Joshua Steffan, PhD
Project Title: "Modulation of Prostate Cancer Metastasis by Prostate Derived ETS Factor (PDEF)"
Institution: University of Colorado School of Medicine
Mentor: Hari Koul, PhD
Sponsor: AUA South Central Section Research Scholar Endowment Fund
The spread of prostate cancer from the prostate is the leading cause of death from prostate cancer. Therefore, the ability for physicians to predict which patients are more likely to have their prostate tumors spread to another organ would influence the selection of treatment options. Dr. Steffan's research will focus on a protein in prostate cells called PDEF (Prostate-Derived ETS Factor), which is progressively lost the more aggressive the prostate tumors become. Therefore, understanding how the PDEF protein decreases in the worst cases of prostate cancer, researchers may be able to one day prevent that decrease and in turn decrease the number of deaths from prostate cancer. Therefore, Dr. Steffan's proposed research asks 1) whether or not different amounts of PDEF can influence the spread of prostate tumors to other organs and 2) how PDEF is either increased or decreased in prostate tumor cells. Understanding these two concepts will significantly contribute to the understanding of the role PDEF plays in the spread of prostate cancer and may one day lead to the use of PDEF as a clinically useful prognostic indicator.
Flaminia Talos, MD, PhD
Project Title: "Directed Differentiation and Transdifferentiation to Prostate and Bladder Epithelia"
Institution: Columbia University Medical Center
Mentor: Michael Shen, PhD
Sponsor: AUA New York Section Research Scholar Endowment Fund
In recent years, the field of stem cell biology became extremely interesting through the breakthrough discovery that only four factors known to maintain embryonic stem cells in an undifferentiated state are also able to "reprogram" terminally differentiated adult cells, such as cells derived from skin connective tissue to a pluripotent state similar to embryonic stem cells. This discovery eliminates the ethical problems related to harvesting and manipulating embryonic stem cells and opens new possibilities for regenerative personalized medicine. However, in order to be used in organ rehabilitation, the induced pluripotent stem cells have to be re-differentiated into desired target tissue, a process which is lengthy and inefficient. Dr. Talos' research proposes to use the same type of approach, i.e., to load tissue-specific master regulator factors into easily accessible cell types in order to re-direct their functionality towards other type of tissues which are not so readily accessible. Specifically, Dr. Talos proposes to convert connective cells from the skin into bladder and prostate epithelium. This would generate new model systems to study prostate epithelial pathologies and would be directly beneficial for patients with bladder exstrophy or who need cystoplasty following surgery for bladder cancer.
Dan Wang, PhD
Project Title: "Role of PRP8 in Regulating AR Intracellular Trafficking in Prostate Cancer Cells"
Institution: University of Pittsburgh
Mentor: Zhou Wang, PhD
Sponsor: AUA Northeastern Section Research Scholar Endowment Fund
The goal of Dr. Wang's research is to identify novel proteins regulating androgen receptor localization and prostate cancer progression to castration-resistance. Prostate cancer is the second most common cause of cancer deaths among men in the U.S., and the androgen receptor (AR) is a key protein in prostate cancer development and progression. In early stage prostate cancer, AR localization is androgen dependent, and the patients are favorably responsive to androgen ablation treatment. As prostate cancer progresses, AR localization becomes androgen-independent and the cancer becomes castration-resistant. Dr. Wang's research will utilize the latest molecular biology techniques to investigate novel proteins regulating AR localization, and examine whether these proteins can restore androgen dependence in advanced prostate cancer. This study is expected to provide insights on mechanisms underlying prostate cancer development and may provide novel therapeutic targets for castration-resistant prostate cancer.
