Associate Professor, Department of Urology
Associate Professor, Department of Physiology & Biophysics
My laboratory is interested in understanding urogenital pathology at the molecular level. The ultimate goal of these investigations is to develop new treatments for, or methods to diagnose, urogenital disease.
Our research is focused on the role of two very different proteins, the MaxiK channel and opiorphins, in urogenital smooth muscle tissue function.
The Slo gene encodes the MaxiK potassium channel, which plays an important role in regulating smooth muscle tone. We have shown the Slo gene is differentially spliced in smooth muscle tissue when animals age or are diabetic- two conditions that result in urogenital pathology. We have found that animals with erectile or bladder dysfunction can be treated using naked gene therapy of vectors expressing the MaxiK channel. These vectors are in clinical trials for the treatment of human erectile or bladder dysfunction.
The other proteins under investigation are opiorphins. The rat homologue of opiorphin (sialorphin) can cause relaxation of corporal smooth muscle tissue, by a mechanism involving inhibition of neutral endopeptidase. We recently discovered that sialorphin can affect GPCR expression and we are determining the relevance of this observation to urogenital physiology- particularly its involvement with erectile dysfunction and priapism.
Publications since 2008
1) Melman, A., Biggs, G., Davies, K.P., Zhao, W.Z., Tar, M.T. and Christ, G.J. (2008) Gene transfer with a vector expressing Maxi-K from a smooth muscle-specific promoter restores erectile function in the aging. Gene Therapy, 15 364-370.
2) Tong, Y., Tiplitsky, S.I., Tar, M.T., Melman, A. and Davies, K.P. (2008) Transcription of G-protein coupled receptors in corporal smooth muscle is regulated by sialorphin (an endogenous neutral endopeptidase inhibitor). J. Urology. 180, 760-766.
3) Yohannes, E., Chang, J., Christ, G.J., Davies, K.P. and Chance, M.R. (2008) Proteomics analysis identifies molecular targets related to diabetes mellitus associated bladder dysfunction. Mol Cell Proteomics, 7, 1270-1285.
4) Melman, A. and Davies, K.P. Gene therapy of the urogenital system (Chapter 91) (2008) Textbook of reconstructive urologic surgery. Ed. Montague, D., Gill, I., Angermeier, K. and Ross, J. Published by Informa Healthcare
5) Davies, K.P. and Melman, A. (2008) Markers of Erectile Dysfunction. Indian J. Urol. 24, 269-274.
6) Tong, Y., Tar, M.T., Melman, A. and Davies, K.P. (2008) The Opiorphin gene (ProL1) and its homologues function in erectile physiology. BJU lnt., 102, 736-740.
7) Davies, K.P. (2009) The Role of Opiorphins (Endogenous Neutral Endopeptidase Inhibitors) in Urogenital Smooth Muscle Biology. J Sex Med.;6 Suppl 3:286-91.
8) Chua, R.G., Calenda, G., Zhang, X., Siragusa, J., Tong, Y, Tar, M., Aydin, M., DiSanto, M.E., Melman, A. and Davies, K.P. (2009) Testosterone Regulates Erectile Function and Vcsa1 Expression in the Corpora of Rats. Mol Cell Endocrinol. 303(1-2):67-73.
9) Calenda, G., Tong, Y, Tar, M., Lowe, D., Siragusa, J., Melman, A. and Davies, K.P. (2009) Vcsa1 acts as a marker of the recovery of erectile function following both gene therapeutic and pharmacological interventions improving erectile function. J Urol. 181(6):2806-15.
10) Sorin, M., Cano, J., Das, S., Mathew, S., Wu, X., Davies, K.P., Shi, X., Cheng, S.W., Ott, D, Kalpana G.V. (2009) Recruitment of a SAP18-HDAC1 complex into HIV-1 virions and its requirement for viral replication. PLoS Pathog. 5(6):e1000463.
11) Melman, A., Zotova, E, Kim, M., Arezzo, J, Davies, K.P., DiSanto, M. and Tar, M. (2009) Longitudinal studies of time dependent changes in both bladder and erectile function after STZ-induced diabetes in the same F344 male rats. BJU Int. 104(9):1292-300.
12) Kanika, N., Tar, M., Tong, Y., Kuppam, D., Melman, A and Davies, K.P. (2009) The mechanism of opiorphin-induced experimental priapism in rats involves activation of the polyamine synthetic pathway. Am J Physiol Cell Physiol. 297(4):C916-27
13) Melman, A and Davies, K.P. (2009) Gene Therapy in the Management of ED; Past, Present and Future. In Press: The Scientific World Journal. 9, 846-54.
14) Christ, G.J., Andersson. K.E., Williams, K., Zhao, W., D’Agostino, R., Kaplan, J., Aboushwareb, T., Yoo, J., Davies, K.P., Calenda, G., Sellers, R. and Melman, A. (2009) Smooth muscle-specific gene transfer with the human Maxi-K channel improves erectile function and enhances sexual behavior in atherosclerotic cynomolgous monkeys. Eur. Urol. 56(6), 1055-1066.
15) Han, G., Tar, M., Kuppam, S., Friedman, A., Melman, A., Friedman, J. and Davies, K.P. (2010) Nanoparticles as a novel delivery vehicle for therapeutics targeting erectile dysfunction. J. Sexual Med. 7, 224-33.
16) Yohannes, E., Chang, J., Tar, M.T., Davies, K.P., and Chance, M.R. (2010) Molecular Targets for Diabetes Mellitus Associated Erectile Dysfunction. Molecular and Cellular Proteomics. 9 (3), 565-78.
17) Melman A, Davies K.P. (2010) Gene therapy for erectile dysfunction: what is the future? Curr Urol Rep;11(6):421-6.
18)Kanika, N.D., Melman, A. and Davies, K.P. (2010). Experimental priapism is associated with increased oxidative stress and activation of protein degradation pathways in corporal tissue. Int J Impot Res;22(6):363-73.
19) Kanika, N., Chang, J., Tong, Y., Tiplitsky, S., Lin, J., Yohannes, J., Tar, M., Chance, M., Christ, G., Melman, A. and Davies, K.P. (2011). Oxidative Stress Status Accompanying Diabetic Bladder Cystopathy Results in the Activation of Protein Degradation Pathways. BJU Int. 2011 May;107(10):1676-84.
20) Calenda, G., Suadicani, S., Iglesias, R., Spray, D., Melman, A., and Davies, K.P. (2011) Silencing MaxiK activity in corporal smooth muscle cells initiates compensatory mechanisms to maintain calcium homeostasis. Aug;8(8):2191-204.
21) Calenda, G., Tong, Y., Kanika, N.D., Tar, M.T., Suadicani, S.O., Xhang, X., Melman, A,, Rougeot, C., Davies, K.P. (2011) Reversal of Diabetic Vasculopathy in a Rat Model of Type 1 Diabetes by Opiorphin-Related Peptides. Am J Physiol Heart Circ Physiol. 301(4):H1353-9.
22) Calenda, G., Strong, T.D., Pavlovich, C.P., Schaeffe,r E.M., Burnett, A.L., Yu, W., Davies, K.P., Bivalacqua, T.J. (2012) Whole genome microarray of the major pelvic ganglion after cavernous nerve injury: new insights into molecular profile changes after nerve injury. BJU Int. 2012 Feb 2. doi: 10.1111/j.1464-410X.2011.10705.x. [Epub ahead of print]
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 742
Bronx, NY 10461
BBC features research by Kelvin Davies, Ph.D., and Joel Friedman, M.D., Ph.D., that highlights using nanoparticles to treat erectile dysfunction.
The Sunday Times (UK) interviews Kelvin Davies, Ph.D., on his involvement in a study that used an innovative new drug-delivery system—nanoparticles infused with nitric oxide and applied topically---to successfully treat erectile dysfunction in animals. The nanoparticle technology was developed by Joel M. Friedman, M.D., Ph.D., professor of physiology & biophysics and of medicine at Einstein and his son, Adam Friedman, M.D., a resident in dermatology in Einstein’s department of medicine. The findings received extensive press coverage at the annual meeting of the American Urological Association on April 26, 2009.