Congratulations to the new 2016-2018 AUA/Urology Care Foundation Research Scholars!
Congratulations to the new 2016-2018 AUA/Urology Care Foundation Research Scholars!
Christina Ching, MD
Project Title: "Role of Reg3 and HIP/PAP on urothelial antimicrobial activity and barrier function against uropathogens"
Institution: The Research Institute at Nationwide Children's Hospital
Mentor: Kirk McHugh, PhD and Michael Becknell, MD
Sponsor: AUA North Central Section Research Scholar Fund I
Childhood urinary tract infections are common and can significantly impact the future health of a child’s urinary tract. The urinary tract possesses a highly specialized lining called the urothelium, which is important in defending the urinary tract against infection and preventing long-term injury of the underlying tissue. Dr. Ching’s research focuses on how the urothelium participates in fighting infection via a specific protein called Reg3γ or HIP/PAP. In particular, her research is investigating how Reg3γ or HIP/PAP could be used to treat various types of infection of the urinary tract and the impact it has on regeneration of the urothelium and its barrier function to outside pathogens.
Paul Dominguez Gutierrez, PhD
Project Title: "Characterization of the Immune Response within Renal Papillary Tips and Peripheral Blood Monocytes of Calcium Oxalate Stone Formers"
Institution: Department of Urology, University of Florida
Mentor: Saeed Khan, PhD and Benjamin Canales, MD, MPH
Sponsor: AUA Southeastern Section Research Scholar Fund III
The immune system is involved with keeping us healthy. It fights of colds and other infections, but it does so much more. It protects us from cancer and even foreign objects- a splinter in the finger is pushed out by the swelling cause by immune response to the splinter. Our group believes that the immune system is involved in keeping our kidneys free of stones by recognizing and destroying the stone in its infancy- the seed. When the immune system fails to destroy the seed, it develops into a kidney stone. We are studying how this seed is recognized and destroyed to eventually develop a therapy to help the immune system destroy the seed before it can become a kidney stone.
Ryan Flannigan, MD
Project Title: "Evaluation of Role of miRNA202-5p in Regulation of Spermatogenesis Using Lecithin:Retinol Acyltransferase (LRAT) Knockout Model"
Institution: Weill Cornell Medical College
Mentor: Darius Paduch, MD, PhD
Sponsor: AUA New York Section E. Darracott Vaughan, MD Research Scholar Fund
Infertility commonly affects 15% of the population worldwide. In half of these cases men are affected, but the etiology remains unknown in 60-75%. In the most severe form of male factor infertility, azoospermia, no sperm are found in the ejaculate. A recent study has identified that microRNA202-5p is significantly down regulated among sertoli cells in these men. The present study will utilize a sertoli cell-only animal model, Lethicin: Retinol Acyltransferase (LRAT) mouse, to evaluate if miRNA202-5p is the cause or result of absent germ cells, and subsequently evaluate mRNA targets of miRNA202-5p. We will then determine if intratesticular injection of a miRNA202-5p inhibitor will suppress spermatogenesis in a normal animal model. This research will aim to uncover important mechanisms of male infertility and provide new potential therapeutic options for infertile men.
Eugene Lee, MD
Project Title: "A carbohydrate restricted diet in patients with diabetes and non-muscle invasive bladder cancer"
Institution: University of Kansas Medical Center
Mentor: Shrikant Anant, PhD and Jeffrey Holzbeierlein, MD
Sponsor: AUA South Central Section Research Scholar Fund I
Patients with diabetes and superficial bladder cancer are at exceptionally high risk of recurrence. Bladder cancer is a tumor type that relies heavily on sugar to grow and multiply making diabetic patients a fertile environment. The goal of our study is to assess whether putting patients with diabetes and bladder cancer on a carbohydrate restricted diet will decrease blood and urine sugar levels translating to less risk of bladder tumor recurrence. At the same time, we will study whether the activity of pyruvate kinase M2, a marker of increased sugar consumption and aggressive cancer, can be changed with reducing sugar availability.
Suk Hyung Lee, PhD
Project Title: "Culture of Patient-derived Bladder Cancer Organoids"
Institution: Columbia University Medical Center
Mentor: Michael Shen, PhD
Sponsor: Society for Urologic Oncology Research Scholar Fund II
Bladder cancer is one of the most common types of cancer in the United States. Recent studies have shown that there is a remarkable variety of types of bladder cancer, suggesting that successful treatments will need to be developed for each individual type. To date, however, there are limited options for bladder cancer treatment, and it has been difficult to tailor therapy for individual patients and their specific bladder cancer types. In this application, I propose to use a new technique to grow tumor samples derived from the bladder tumors of individual patients. These tumor samples can be grown in the laboratory to form living organoids, which mimic key features of the tumors from which they are grown. These organoids will be used for analyses to determine their specific bladder cancer subtype and tested to determine which drugs might represent effective treatments. Thus, the long-term objective of this study is to provide the basis for developing personalized treatments for patients with bladder cancer.
Scott Manson, PhD
Project Title: "The Development of Peptide-based Therapies for Calcium Oxalate Stone Disease"
Institution: Washington University
Mentor: Paul Austin, MD
Sponsor: Endourological Society Research Scholar Fund
Kidney stone disease is a prevalent condition (~12% of the population) with significant adverse consequences, few effective therapeutic options, and a high likelihood for recurrence. The majority of kidney stones result from the formation of calcium oxalate crystals in the urine that subsequently adhere to proteins on the surface of renal epithelial cells, affording them time to grow into debilitating stones that impair kidney function. The goal of this project is to identify the precise biochemical mechanisms that mediate binding of calcium oxalate crystals to renal epithelial cells during stone formation. The proposed research is likely to have considerable implications for the treatment of stone disease by identifying a specific therapeutic target for the development of peptide-based therapies to inhibit stone formation/recurrence in at-risk individuals, limit stone growth in affected individuals, and prevent the deleterious, long-term effects of stone disease.
Laura Mike, PhD
Project Title: "Therapeutic strategies targeting uropathogenic Escherichia coli iron acquisition"
Institution: University of Michigan
Mentor: Harry Mobley, PhD
Sponsor: Dornier MedTech
Over 4 million women in the U.S. suffer from continual urinary tract infections (UTIs) annually. The long-term antibiotic regimens required to control UTIs has caused a rise in antibiotic resistant bacteria and highlights the need for novel therapeutic strategies. Overwhelming evidence indicates that preventing bacteria from acquiring the important nutrient metal, iron, may prevent or inhibit UTIs. The research outlined here focuses on identifying new strategies for blocking bacterial iron acquisition using pharmaceutical- and vaccine-based approaches.
Ranjith Ramasamy, MD
Project Title: "Leydig Stem Cell Autograft for Treatment of Hypogonadism in Klinefelter Syndrome"
Institution: University of Miami
Mentor: Joshua Hare, MD and Dipen Parekh, MD
Sponsor: Sexual Medicine Society of North America
Klinefelter Syndrome is the most common chromosomal abnormality in men. Characterized with an extra X chromosome, men with Klinefelter syndrome have testicular failure leading to infertility and low testosterone. Low testosterone can lead to adverse effects such as decreased bone density, delayed puberty, gynecomastia and poor sexual function. The current standard of care for men with Klinefelter syndrome and low testosterone is lifelong testosterone therapy. Testosterone therapy can lead to impaired fertility and assisted reproduction outcomes in men with Klinefelter syndrome. The project proposes developing a novel treatment modality: Leydig stem cell autograft for treatment of low testosterone. The stem cells can increase testosterone without affecting fertility outcomes. We also will identify the mechanism for low testosterone so novel therapeutic targets for increasing testosterone can be identified.
Mirja Rotinen, PhD
Project Title: "Onecut2: A Novel Master Regulator Transcription Factor Predicted to be Highly Active in Castration-resistant Prostate Cancer"
Institution: Cedars-Sinai Medical Center
Mentor: Michael Freeman, PhD
Sponsor: Chesapeake Urology Associates Research Scholar Fund
When prostate cancer progresses to resistance to current therapeutic options, the disease inevitably becomes fatal to patients. We have identified a novel protein, Onecut2 that is likely to be a master regulator of this phase of the disease. In this project I will try to understand how this protein operates. Identification of prostate tumors where Onecut2 activity is high may provide new means of patient stratification and novel therapeutic options.
Hosu Sin, PhD
Project Title: "Elucidating fundamental regulators of male meiosis"
Institution: Stanford Univsersity, School of Medicine
Mentor: Margaret Fuller, PhD
Sponsor: AUA Western Section Research Scholar Fund II
In sexually reproducing eukaryotes, meiosis is essential to convert a diploid cell to haploid gametes. Disruptions of this process result in a wide range of human diseases such as male infertility, spontaneous miscarriage, and birth defects including aneuploidy disorders. I am particularly interested in the mechanism underlying male germ cell development, which is an essential process to produce haploid gametes. In this proposal, I seek to discover key regulators that govern meiotic progression and differentiation of male gametes, which will provide basic knowledge and new insight to understand these diseases.
Geoff Sonn, MD
Project Title: "Metabolic Profiling of Aggressive Prostate Cancer Using Desorption Electrospray Ionization Mass Spectrometric Imaging"quot;
Institution: Stanford University
Mentor: Richard Zare, PhD and James Brooks, MD
Sponsor: Society for Urologic Oncology Research Scholar Fund I
Better tools are urgently needed to differentiate indolent from aggressive prostate cancer to enable personalized decision making about treatment. A new technique, called desorption electrospray ionization (DESI) mass spectrometry imaging (MSI), has been developed that can rapidly measure hundreds of molecules in fresh tissue specimens. This method can rapidly and accurately diagnose cancer in other tumor types but its utility has not been tested in prostate cancer. Dr. Sonn’s early results show the ability to identify aggressive human prostate cancer using DESI-MSI and he now proposes to build upon these results to develop DESI-MSI as a new tool to assess prostate cancer aggressiveness.
Adriana Vidal, PhD
Institution: Cedars-Sinai Medical Center
Mentor: Stephen Freedland, MD
Sponsor: Robert J. Krane, MD Research Scholar Fund
It is estimated, that 1 in every 6 men in the United States will be diagnosed with prostate cancer during their lifetime, and African American men have the highest incidence and mortality rates in the world. Recent evidence suggests that both systemic and prostatic inflammation may play a role in prostate carcinogenesis. However, most studies evaluating the association between prostate cancer risk and inflammation have been performed in Caucasian men. Given that an elevated PSA level in a healthy man is often the first sign of prostate cancer and higher levels correlate with greater risk, these data suggest systemic inflammatory markers may be linked with prostate cancer risk. In this proposal, I will expand these early observations using a multiethnic cohort, which includes ~45% African American men, to test the association between systemic inflammatory markers and prostate cancer risk and progression. This will fill a major gap in our knowledge given no studies to date have examined the association between markers of systemic inflammation and prostate cancer in men of African origin.
Kyle Wood, MD
Project Title: "Glyoxal: A Novel Source of Endogenous Oxalate Synthesis and Its Clinical Contribution to Kidney Stones"
Institution: University of Alabama at Birmingham
Mentor: Dean Assimos, MD and Ross Holmes, PhD
Sponsor: Boston Scientific, Inc., The Endourological Society, and the "Friends of Joe"
My research project is looking at a novel pathway in oxalate formation. Oxalate is a component of the most common type of kidney stone. Elucidating this pathway may lead to novel treatment options for individuals afflicted with kidney stone disease.