The NYU Urology research team is comprised of two basic molecular scientists with primary appointments in Urology, three basic scientists with secondary appointments in Urology, a medical oncologist, a medical geneticist, a uropathologist, five clinician scientists and ten basic scientists collaborating with our department.

Paul Walden, Ph.D., Associate Professor of Urology and Biochemistry directs laboratory research studying prostate growth regulation. Dr. Walden’s research, which is funded by the NIH, DOD and private industry, currently focuses on two lines of investigation. One project addresses the regulation of prostate growth by the sympathetic and sensory nervous systems. Using animal models and human tissue and cell lines, they are studying the growth promoting signaling pathways activated in prostate by sympathetic and sensory neurotransmitters. The second project is concerned with identifying the molecular events involved in the initiation and progression of prostate cancer that represent putative therapeutic targets. Dr. Walden has identified BTG2 as a tumor suppressor lost due to increased protein degradation as an early event in prostate carcinogenesis. BTG2 fulfils a significant component of the p53-dependent DNA damage repair pathway as evidenced by the observation that in contrast to control cells BTG2 null cells continue to proliferate in the presence of DNA damaging agents. Thus loss of BTG2 in prostate cells has important implications for accrual of genetic damage and disease progression. Dr. Walden’s group is examining the cellular mechanisms that regulate BTG2 protein levels as well as identifying therapeutic approaches to increase BTG2 levels in prostate cancer.

Dr. Tung-Tien Sun, Professor of Dermatology, Pharmacology and Urology
Tung-Tien Sun, PhD, is Professor of Urology and Pharmacology, Rudolf L. Baer Professor of Dermatology, and Director of the Epithelial Biology Unit of the Department of Dermatology at NYU School of Medicine. He is interested in the growth and differentiation of mammalian epithelia. He and his collaborators have established keratins as molecular markers for different pathways and stages of epithelial differentiation; identified corneal epithelial and hair follicular epithelial stem cells; and discovered uroplakins as the major differentiation products of mammalian urothelium. He and his collaborators are currently studying the structure, function and disease implications of uroplakins using cell and molecular biologic approaches. He has received the Alcon Award in Vision Research and Montagna Lectureship of the Society of Investigative Dermatology, and he has given the the SC Liu Lecture at Stanford Medical School, the Susan Swerling Lecture at Harvard Medical School, the William W. Scott Lecture at Johns Hopkins Medical School, and the Dean’s Lecture at NYU Medical School.

Dr. Xue-Ru Wu, Associate Professor of Urology and Microbiology, has been studying urinary bladder biology and diseases for the past 15 years. He and his collaborator, Dr. Tung-Tien Sun, Professor of Dermatology, Pharmacology and Urology, discovered a group of proteins that they named uroplakins. These proteins are the only bladder-specific markers, and can be used not only for understanding bladder growth and differentiation, but also for better diagnosing bladder cancer. Dr. Wu is an integral member of a 6.6 million dollar program project supporting bladder research at NYU. This is the largest bladder project supported by the NIH. Dr. Wu's laboratory has recently generated the first transgenic mouse models of bladder tumorigenesis. These models can serve as important in vivo platform for studying the molecular pathways of bladder cancer formation and for testing novel preventive and therapeutic strategies. In addition, Dr. Wu's group has demonstrated that uroplakins Ia and Ib, two major protein subunits of urothelial apical plaques, can serve as the receptors for type 1-fimbriated E. Coli. Dr. Wu, in collaboration with David Hasty of University of Tennessee, Memphis, showed that a uropathogenic FimH variant, but not a fecal FimH variant, preferentially binds to the uroplakin I receptors, indicating that these receptors provide a selective advantage for specific group of E. Coli in the urinary tract. Finally, Dr. Wu is actively pursuing the functional roles of Tamm-Horsfall protein, the most abundant protein in human urine, in defending the urinary tract against bacterial infections and stone formation. His group developed a gene knockout model for this protein and is in the process of a series of biological and genetic studies aiming at elucidating the function of this protein in urinary physiology and diseases. Dr. Wu's research is being supported by a Veterans Administration's merit review grant, NIH grants, and departmental research fund.

Dr. Samir Taneja's laboratory focuses on delineating the mechanism by which androgens initiate prostate cancer growth. Although the growth dependence of prostate cancer upon androgens has long been understood, very little is known in regard to the specific molecular mechanism by which mitogenic action occurs. Androgens act through binding of the androgen receptor (AR), a ligand-activated transcription factor capable of either transcriptional activation or repression of specific target genes. Upon binding dihydrotestosterone, the AR dimerizes into an active form, crosses the nuclear membrane, and binds to specific DNA sequences, termed androgen response elements (ARE), within the promoter region of target genes. Binding of the ARE by AR results in activation of transcription at the promoter site. Ultimately, in the case of prostate cancer, the activation and/or repression of specific target genes results in cellular growth through undefined signaling pathways.

Dr. Taneja's research is focused upon the delineation of AR's growth signaling pathway. Dr. Taneja was recently awarded a KO-8 grant by the NIH to support his laboratory research. This, to date, has resulted in three specific projects: 1) identification and characterization of AR coactivators involved in transcriptional activation; 2) characterization of the response of cell cycle regulatory molecules to androgen stimulation in prostate cancer; and 3) identification of AR target genes. Initial studies resulted in the identification of several putative coactivator proteins interacting with the N-terminal region of the AR. Characterization of these proteins, along with an assessment of their role in prostate growth and differentiation, is ongoing. The second project has identified a unique pattern of cell cycle regulation in malignant prostate cells. This implicates specific cell cycle regulators as the mediators of androgen-dependent prostate cancer growth. Current studies focus upon the delineation of a mechanism to explain the observed findings.

Finally, gene therapy remains one of Dr. Taneja’s research interests. Current projects in the laboratory focus upon the characterization unique viral vectors that can be used to administer such therapies. These studies attempt to address the longstanding problems of viral vectors such as tissue targeting and immune tolerance.

It is beyond the scope of this residency brochure to summarize the other urology related research programs at NYU. The list of NIH funding provides a reference to these projects.

Susan Logan, PhD., Assistant Professor of Urology and Pharmacology studies the androgen receptor signal transduction pathway. The specific goals of the lab are to: 1) uncover the role of androgen receptor binding proteins (coactivators and corepressors) in androgen-mediated prostate cell growth 2) develop new mouse models of prostate cancer progression and 3) utilize phosphorylation site-specific androgen receptor antibodies to define the functional role of androgen receptor in androgen-dependent and androgen-independent prostate cancer. One study recently completed in the laboratory describes Androgen Receptor Trapped clone-27 (ART-27) a transcriptional coactivator of the androgen receptor (AR) N-terminus. During prostate development in humans, ART-27 is expressed in differentiated luminal epithelial cells but is not detected in undifferentiated epithelial cell precursors, suggesting a role for ART-27 in AR-mediated growth suppression and differentiation. Consistent with a growth suppressive function, ART-27 expression levels are negligible in human prostate cancer and regulated expression of ART-27 in the androgen sensitive LNCaP prostate cancer cell line inhibits androgen-mediated cellular proliferation. Moreover, a somatic alteration in AR associated with prostate cancer (AR P340L) shows a diminished capacity to enhance ART-27 mediated AR-transcriptional activation. Thus, ART-27 is a novel AR cofactor that interacts with the AR N-terminus, where it plays a role in facilitating receptor-induced transcriptional activation and, interestingly, displays both cell type and developmental regulation in humans suggestive of a role in AR-dependent differentiation. Congressionally Directed Medical Research Program in Prostate Cancer, The Concern Foundation and an NYU Cancer Center Translational Research Grant currently support Dr. Logan’s research.

Chuan-Guo Xiao, M.D., Assistant Professor of Urologic Research, is a graduate of Tongji Medical University of China and is a AUA fellow of Neurology & Reconstructive Urology from Eastern Virginia Medical School, Norfolk, VA. He is actively engaged in pioneering research regarding creation of a somatic-autonomic reflex pathway for treatment of neurogenic bladder in patients with spinal cord injury.