Throughout the laboratories of the Department of Urology and its collaborators, basic research is under way to better understand the origins and progression of urologic disease and to develop potential new therapies.
- Urothelial biology
- Bladder cancer
- Urinary stone disease
- Genitourinary development
- Prostate cancer & the androgen receptor
The Sun Laboratory and collaborators focus on understanding the structure and function of epithelial cells, which line the surface of the entire lower urinary tract where they are known as urothelium. The Sun laboratory identified a group of urothelial membrane proteins, called uroplakins, that are made by mammalian bladder urothelium as major differentiation products. These molecules are useful markers for bladder cancer, and the uroplakin promoter can be used to generate transgenic models of bladder tumorigenesis. In addition, uroplakin defects may lead to a number of important urinary tract abnormalities.
Dr. Xue-Ru Wu’s laboratory focuses on the molecular pathogenesis of bladder cancer. The group studies uroplakins, a bladder-specific marker found on the surface of cells lining the lower urinary tract. Dr. Wu and colleagues have found that two uroplakins can serve as major urothelial receptors for the variety of E. coli that cause 85% of urinary tract infections. In addition, the group has developed transgenic mouse models of bladder tumorigenesis by specifically expressing activated oncogenes and mutated tumor suppressor genes in bladder epithelium.
Urinary stone disease
Dr. Xue-Ru Wu leads a group of researchers investigating the role of several key urinary macromolecules in defending against the formation of urinary stones (kidney stones). Hypothesizing that physiological defects may have a role in the recurrent development of kidney stones, the group has found recently that deficiency in Tamm-Horsfall protein, the most abundant urinary protein made by renal epithelial cells, and that osteopontin, a regulator of bio-mineralization in bone, can lead to increased production of renal calcium crystals in mice. These studies have great potential implications for a molecular approach to diagnose recurrent urinary stone disease and for devising preventive strategies for this exceedingly common and important disease.
Dr. Ellen Shapiro and Dr. Irina Grishina, in partnership with Dr. Harry Ostrer and Dr. Susan Logan, are exploring the mechanisms of developing genitourinary organs, particularly the prostate, bladder and testis. The group has explored the role of signaling molecules, receptors and growth factors in the development of the fetal prostate, including BMP7, androgen receptor and Notch1. These studies have provided important insights related to the regulation of prostatic growth and, ultimately, into the regulation of prostate diseases. In a related project, Dr. Grishina and Dr. Shapiro are using knockout mice deficient in BMP7 to gain insights into human urogenital abnormalities.
Regulation of the androgen receptor in prostate cancer
NYU Urology researchers and their colleagues in other departments at NYU School of Medicine are working to uncover the role of androgen receptor (AR) signaling in prostate cancer. Their work includes evaluating the role of AR cofactor ART-27 in prostate cancer growth; examining the role of an AR cofactor called ARA70 beta; and investigating AR phosphorylation as a potential new diagnostic and therapeutic tool.