David A Moscatelli

Biosketch / Results /

David Moscatelli

Professor, Department of Cell Biology
Instructor-Cell Biology & Histology

Contact Info

Address
550 First Avenue
New York, NY 10016

David.Moscatelli@nyumc.org

Research Summary

My research explores the interplay between the prostate and its vasculature and how the balance of signals between these two compartments is disturbed in prostate cancer. The prostate is an androgen-sensitive organ: it regresses upon androgen withdrawal (e.g. castration) and regenerates after androgen repletion. One of the first cell compartments to respond to androgen withdrawal is the vascular endothelium. Prostate capillary endothelial cells begin to undergo apoptosis within 24 h after androgen ablation. Similarly, the blood vessel endothelium is one of the first cell compartments to initiate DNA synthesis after androgen repletion. These observations led us to propose that endothelial cell growth factors may be under androgen regulation in the prostate. We have found that the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) is regulated by androgen in prostate. We have also found that blocking VEGF signals inhibits expansion of the vasculature in castrated animals given androgen and blocks the regeneration of the organ. Similarly, overexpression of VEGF in androgen-regulated prostate tumor cells can convert them to androgen-independent growth. These findings suggest that VEGF is one of the key modulators of the prostate response to androgen. We are also exploring the role of another class of signaling molecules, the angiopoietins, in prostate growth. Angiopoietin-1 binds to the tie-2 receptor, which is restricted to endothelial cells, and promotes vascular maturation. A related molecule, angiopoietin-2, also binds to tie-2 but does not transmit a signal, thereby acting as a competitive inhibitor of angiopoietin-1. Although angiopoietin-1 has been thought to act primarily on endothelial cells, we have found that it can directly affect the growth of prostate epithelial cells. We are currently exploring the interaction between angiopoietin-1 and angiopoietin-2 in the regulation of prostate epithelial growth and prostate vascular growth. Finally, we are examining the relationship between the prostatic vasculature and prostatic stem cells. We have found that vascular density is highest in the proximal region of the prostate, where the stem cells reside. Current research explores the signals from the stem cells that might regulate the vascular density in this region. In addition, we will determine if altering the vascular supply in the proximal region alters its ability to harbor stem cells.

Research Interests

Regulation of Vascular Growth Factors in the Prostate

Bmi-1, stem cells and prostate carcinogenesis
Moscatelli, David; Lynette Wilson, E. Bmi-1, stem cells and prostate carcinogenesis. Asian journal of andrology. 2011 Feb 21;13(3):353-354 (131955)

Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways. L
Blum, Roy; Gupta, Rashmi; Burger, Patricia E; Ontiveros, Christopher S; Salm, Sarah N; Xiong, Xiaozhong; Kamb, Alexander; Wesche, Holger; Marshall, Lisa; Cutler, Gene; Wang, Xiangyun; Zavadil, Jiri; Moscatelli, David; Wilson, E Lynette. Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways. L. PLoS one. 2010 Sep 30;5(9):?-? (113814)

PINing Down the Origin of Prostate Cancer
Moscatelli, David; Wilson, E Lynette. PINing Down the Origin of Prostate Cancer. Science translational medicine. 2010 Aug 4;2(43):43ps38-43ps38 (111550)

Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer
Blum, Roy; Gupta, Rashmi; Burger, Patricia E; Ontiveros, Christopher S; Salm, Sarah N; Xiong, Xiaozhong; Kamb, Alexander; Wesche, Holger; Marshall, Lisa; Cutler, Gene; Wang, Xiangyun; Zavadil, Jiri; Moscatelli, David; Wilson, E Lynette. Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. PLoS one. 2009 May 29;4(5):e5722-e5722 (99241)

High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem/progenitor cells
Burger, Patricia E; Gupta, Rashmi; Xiong, Xiaozhong; Ontiveros, Christopher S; Salm, Sarah N; Moscatelli, David; Wilson, E Lynette. High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem/progenitor cells. Stem cells. 2009 Sep ;27(9):2220-2228 (948112)