Carol Ann Podlasek

Carol Ann Podlasek, PhD
Assistant Professor
Urology

Sonic hedgehog (SHH) signaling in penile development and erectile dysfunction

Research clusters: Cellular and Molecular Biology
Reproductive Science

E-mail:   
cap325@northwestern.edu  

Significantly increased smooth muscle and endothelial apoptosis accompanies both diabetes progression and cavernous nerve (CN) injury.  These penile morphology changes play a critical role in the development of erectile dysfunction (ED).  The protein Sonic hedgehog (Shh) is significantly decreased in both of these impotence models.  We propose that decreased Shh protein observed in these rat models may cause significantly elevated apoptosis observed post CN injury.  Animal studies are in progress, which examine the potential of Shh to be developed as a treatment for CN injury induced apoptosis.  Future studies will focus on the mechanism of how Shh suppresses CN injury induced apoptosis and how the apoptosis signal is transduced. 
Nano-technology for the targeted delivery of Shh as a treatment for ED has been initiated as a collaborative study with Daniel Harrington, Ph.D. at RICE, Samuel Stupp, Ph.D. in the Bionanotechnology Department at Northwestern University and Kevin McKenna in the Department of Physiology at Northwestern University.  These studies will characterize the distribution of the nanoparticles upon injection into the penis, strength of the scaffold and immunogenic response of the rat corpora cavernosa in vivo.  These studies are translational since PA’s for human Shh protein will be developed that can be injected at the time of prostatectomy to prevent apoptosis and penile morphology changes that cause ED when the cavernous nerve is injured.
Studies are in progress that will examine how Shh signaling is regulated in the penis.  We believe from preliminary experiments that neural input plays a crucial role in this process.  Future studies will investigate the role that the pelvic ganglia plays in maintaining Shh signaling and smooth muscle morphology in the corpora cavernosa.

Selected Publications:
Angeloni NL, Bond CW, Monsivais D, Tang Y, Podlasek CA.  The Role of Hedgehog-interacting Protein in Maintaining Cavernous Nerve Integrity and Adult Penile Morphology.  J Sexual Medicine 2009; 6: in press.

Podlasek CA.  Sonic hedgehog, Apoptosis and the Penis.  J Sexual Medicine 2009; 6 (suppl 3): 334-339.  PMID: 19267857.2.

Modder J, Podlasek CA, McVary KT.  Pathophysiology of Erectile Dysfunction Following Radical Prostatectomy.  In: Sexual Function in the Prostate Cancer Patient, Mulhall J (Ed), Humana Press, Totowa, NJ, 2009; 268: 34-47.  ISBN: 978-1-60327-554-5.

 Bond C, Tang Y, Podlasek CA.  Neural Regulation of Sonic Hedgehog and Apoptosis in the Penis.  Biol. Reprod 2008; 78: 947-956.  PMID: 18256331.

Podlasek CA, Meroz CL, Tang Y, Wood D, McKenna KE, McVary KT.  Regulation of cavernous nerve injury-induced apoptosis by Sonic hedgehog.  Biol Reprod 2007; 76:19-28.  PMID: 16988214.

 Podlasek CA, Meroz CL, Korolis H, Tang Y, McKenna KE, McVary KT.  Sonic Hedgehog, the Penis and Erectile Dysfunction: A Review of Sonic hedgehog Signaling in the Penis.  Current Pharmaceutical Design 2005; 11 (31): 4011-4027.  PMID: 16378507.

Podlasek CA, Zelner DJ, Harris JD, Meroz CL, Tang Y, McKenna KE, and McVary KT.  Altered Sonic Hedgehog Signaling Is Associated with Morphological Abnormalities in the Penis of the BB/WOR Diabetic Rat.  Biol Reprod 2003; 69: 816-827.  PMID: 12748119.

Podlasek CA, Zelner DJ, Jiang HB, Tang Y, Houston J, McKenna KE, McVary KT.  Sonic hedgehog Cascade is Required for Penile Postnatal Morphogenesis, Differentiation and Adult Homeostasis.  Biol. Reprod 2003; 68: 423-438.  PMID: 12533405.


PubMed website

View Publications by Carol Podlasek listed in the National Library of Medicine (PubMed).