Robert M. Weiss, MD, FACS, FAAP

Research Interests

Urinary Bladder Neoplasms; Pharmacology; Urology; Signal Transduction

Research Organizations

Urology

Faculty Research

Yale Cancer Center: Signal Transduction

Office of Cooperative Research

Research Summary

We are involved in using nano-particle delivery systems to diagnose and treat diseases of the urinary system with special emphasis on benign and malignant diseases of the bladder. These studies, which are presently focused on diagnosing and treating bladder and prostate cancer utilizing nano-particles loaded with specifically targeted siRNAs are directed by Darryl T. Martin, PhD. In addition we are studying the pharmacology and physiology on ureteral-vesical smooth muscle.

Specialized Terms: muscle pharmacology; Signal transduction; Bladder cancer; Drug delivery

Extensive Research Description

The Proof of Concept that we are testing is that intravesical instillation of small interference RNA (siRNA) packaged in biodegradable nanospheres provides wide opportunities for the treatment of urologic diseases including transitional cell carcinoma of the bladder (TCC), interstitial cystitis (IC), overactive bladder, and detrusor hyperreflexia.

Because of their robust, gene selective silencing of target protein expression, siRNA oligonucleotides are an attractive therapeutic option with high selectivity and specificity and minimal toxicity to neighboring cells. siRNAs, however, have a relatively short half-life and thus we are addressing the stabilization and intravesical delivery of siRNAs. To achieve this goal, we plan to create and test clinically viable, non-viral nanosphere siRNA complexes that are intravesically
instilled for treatment of diseases of the urinary tract.

We plan to develop and test a number of nanoparticle controlled release systems containing targeting proteins that will stabilize and deliver siRNAs and drugs and initially test these on bladder cancers

Using nanospheres that contain siRNAs to survivin in combination with chemotherapeutic agents to affect growth and spread of bladder cancer in in vitro and in vivo animal models

Use of nanoparticles for localization and treatment of prostatic carcinoma in a in vivo animal model.

Full List of PubMed Publications

• Hu SL, Chang A, Perazella MA, Okusa MD, Jaimes EA, Weiss RH, American Society of Nephrology Onco-Nephrology Forum.: The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma. J Am Soc Nephrol. 2016 Aug; 2016 Mar 9. PMID: 26961346
• Hser YI, Evans E, Huang D, Weiss R, Saxon A, Carroll KM, Woody G, Liu D, Wakim P, Matthews AG, Hatch-Maillette M, Jelstrom E, Wiest K, McLaughlin P, Ling W: Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial. Addiction. 2016 Apr; 2016 Jan 13. PMID: 26599131
• Schwantes-An TH, Zhang J, Chen LS, Hartz SM, Culverhouse RC, Chen X, Coon H, Frank J, Kamens HM, Konte B, Kovanen L, Latvala A, Legrand LN, Maher BS, Melroy WE, Nelson EC, Reid MW, Robinson JD, Shen PH, Yang BZ, Andrews JA, Aveyard P, Beltcheva O, Brown SA, Cannon DS, Cichon S, Corley RP, Dahmen N, Degenhardt L, Foroud T, Gaebel W, Giegling I, Glatt SJ, Grucza RA, Hardin J, Hartmann AM, Heath AC, Herms S, Hodgkinson CA, Hoffmann P, Hops H, Huizinga D, Ising M, Johnson EO, Johnstone E, Kaneva RP, Kendler KS, Kiefer F, Kranzler HR, Krauter KS, Levran O, Lucae S, Lynskey MT, Maier W, Mann K, Martin NG, Mattheisen M, Montgomery GW, Müller-Myhsok B, Murphy MF, Neale MC, Nikolov MA, Nishita D, Nöthen MM, Nurnberger J, Partonen T, Pergadia ML, Reynolds M, Ridinger M, Rose RJ, Rouvinen-Lagerström N, Scherbaum N, Schmäl C, Soyka M, Stallings MC, Steffens M, Treutlein J, Tsuang M, Wall TL, Wodarz N, Yuferov V, Zill P, Bergen AW, Chen J, Cinciripini PM, Edenberg HJ, Ehringer MA, Ferrell RE, Gelernter J, Goldman D, Hewitt JK, Hopfer CJ, Iacono WG, Kaprio J, Kreek MJ, Kremensky IM, Madden PA, McGue M, Munafò MR, Philibert RA, Rietschel M, Roy A, Rujescu D, Saarikoski ST, Swan GE, Todorov AA, Vanyukov MM, Weiss RB, Bierut LJ, Saccone NL: Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behav Genet. 2016 Mar; 2015 Sep 21. PMID: 26392368
• Yu D, Mathews CA, Scharf JM, Neale BM, Davis LK, Gamazon ER, Derks EM, Evans P, Edlund CK, Crane J, Fagerness JA, Osiecki L, Gallagher P, Gerber G, Haddad S, Illmann C, McGrath LM, Mayerfeld C, Arepalli S, Barlassina C, Barr CL, Bellodi L, Benarroch F, Berrió GB, Bienvenu OJ, Black DW, Bloch MH, Brentani H, Bruun RD, Budman CL, Camarena B, Campbell DD, Cappi C, Silgado JC, Cavallini MC, Chavira DA, Chouinard S, Cook EH, Cookson MR, Coric V, Cullen B, Cusi D, Delorme R, Denys D, Dion Y, Eapen V, Egberts K, Falkai P, Fernandez T, Fournier E, Garrido H, Geller D, Gilbert DL, Girard SL, Grabe HJ, Grados MA, Greenberg BD, Gross-Tsur V, Grünblatt E, Hardy J, Heiman GA, Hemmings SM, Herrera LD, Hezel DM, Hoekstra PJ, Jankovic J, Kennedy JL, King RA, Konkashbaev AI, Kremeyer B, Kurlan R, Lanzagorta N, Leboyer M, Leckman JF, Lennertz L, Liu C, Lochner C, Lowe TL, Lupoli S, Macciardi F, Maier W, Manunta P, Marconi M, McCracken JT, Mesa Restrepo SC, Moessner R, Moorjani P, Morgan J, Muller H, Murphy DL, Naarden AL, Nurmi E, Ochoa WC, Ophoff RA, Pakstis AJ, Pato MT, Pato CN, Piacentini J, Pittenger C, Pollak Y, Rauch SL, Renner T, Reus VI, Richter MA, Riddle MA, Robertson MM, Romero R, Rosário MC, Rosenberg D, Ruhrmann S, Sabatti C, Salvi E, Sampaio AS, Samuels J, Sandor P, Service SK, Sheppard B, Singer HS, Smit JH, Stein DJ, Strengman E, Tischfield JA, Turiel M, Valencia Duarte AV, Vallada H, Veenstra-VanderWeele J, Walitza S, Wang Y, Weale M, Weiss R, Wendland JR, Westenberg HG, Shugart YY, Hounie AG, Miguel EC, Nicolini H, Wagner M, Ruiz-Linares A, Cath DC, McMahon W, Posthuma D, Oostra BA, Nestadt G, Rouleau GA, Purcell S, Jenike MA, Heutink P, Hanna GL, Conti DV, Arnold PD, Freimer NB, Stewart SE, Knowles JA, Cox NJ, Pauls DL: Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am J Psychiatry. 2015 Jan; 2014 Oct 31. PMID: 25158072
• Crawford FW, Weiss RE, Suchard MA: SEX, LIES AND SELF-REPORTED COUNTS: BAYESIAN MIXTURE MODELS FOR HEAPING IN LONGITUDINAL COUNT DATA VIA BIRTH-DEATH PROCESSES. Ann Appl Stat. 2015. PMID: 26500711
• Gupta R, Dong Y, Solomon PD, Wettersten HI, Cheng CJ, Min JN, Henson J, Dogra SK, Hwang SH, Hammock BD, Zhu LJ, Reddel RR, Saltzman WM, Weiss RH, Chang S, Green MR, Wajapeyee N: Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proc Natl Acad Sci U S A. 2014 Jul 29; 2014 Jul 14. PMID: 25024194
• Martin DT, Steinbach JM, Liu J, Shimizu S, Kaimakliotis HZ, Wheeler MA, Hittelman AB, Mark Saltzman W, Weiss RM: Surface-modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer. Mol Cancer Ther. 2014 Jan; 2013 Nov 12. PMID: 24222663
• Martin DT, Hoimes CJ, Kaimakliotis HZ, Cheng CJ, Zhang K, Liu J, Wheeler MA, Kelly WK, Tew GN, Saltzman WM, Weiss RM: Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer. Nanomedicine. 2013 Nov; 2013 Jun 11. PMID: 23764660
• Weiss RM, Guo S, Shan A, Shi H, Romano RA, Sinha S, Cantley LG, Guo JK: Brg1 determines urothelial cell fate during ureter development. J Am Soc Nephrol. 2013 Mar; 2013 Feb 28. PMID: 23449535
• Verma A, Degrado J, Hittelman AB, Wheeler MA, Kaimakliotis HZ, Weiss RM: Effect of mitomycin C on concentrations of vascular endothelial growth factor and its receptors in bladder cancer cells and in bladders of rats intravesically instilled with mitomycin C. BJU Int. 2011 Apr; 2010 Aug 24. PMID: 20735383
• Yono M, Mane SM, Lin A, Weiss RM, Latifpour J: Differential effects of diabetes induced by streptozotocin and that develops spontaneously on prostate growth in Bio Breeding (BB) rats. Life Sci. 2008 Aug 1; 2008 Jun 20. PMID: 18619471
• Reiner E, Pollak JS, Henderson KJ, Weiss RM, White RI Jr: Initial experience with 3% sodium tetradecyl sulfate foam and fibered coils for management of adolescent varicocele. J Vasc Interv Radiol. 2008 Feb. PMID: 18341950
• Takizawa BT, Uchio EM, Cohen JJ, Wheeler MA, Weiss RM: Downregulation of survivin is associated with reductions in TNF receptors' mRNA and protein and alterations in nuclear factor kappa B signaling in urothelial cancer cells. Cancer Invest. 2007 Dec. PMID: 18058462
• Yono M, Foster HE Jr, Weiss RM, Latifpour J: Age related changes in the functional, biochemical and molecular properties of alpha1-adrenoceptors in the rat genitourinary tract. J Urol. 2006 Sep. PMID: 16890728
• Weiss RM, Tamarkin FJ, Wheeler MA: Pacemaker activity in the upper urinary tract. J Smooth Muscle Res. 2006 Aug. PMID: 17099294
• Tamarkin FJ, Kang WS, Cohen JJ, Wheeler MA, Weiss RM: A role for Akt in the rapid regulation of inflammatory and apoptotic pathways in mouse bladder. Naunyn Schmiedebergs Arch Pharmacol. 2006 Aug; 2006 Jul 11. PMID: 16832691
• Yono M, Pouresmail M, Takahashi W, Flanagan JF, Weiss RM, Latifpour J: Effect of insulin treatment on tissue size of the genitourinary tract in BB rats with spontaneously developed and streptozotocin-induced diabetes. Naunyn Schmiedebergs Arch Pharmacol. 2005 Nov; 2005 Oct 19. PMID: 16235050
• Renzulli JF 2nd, Shetty R, Mangray S, Anderson KR, Weiss RM, Caldamone AA: Clinical and histological significance of the testicular remnant found on inguinal exploration after diagnostic laparoscopy in the absence of a patent processus vaginalis. J Urol. 2005 Oct. PMID: 16148657
• Wheeler MA, Ayyagari RR, Wheeler GL, Weiss RM: Regulation of cyclic nucleotides in the urinary tract. J Smooth Muscle Res. 2005 Feb. PMID: 15855736
• Kang WS, Tamarkin FJ, Wheeler MA, Weiss RM: Rapid up-regulation of endothelial nitric-oxide synthase in a mouse model of Escherichia coli lipopolysaccharide-induced bladder inflammation. J Pharmacol Exp Ther. 2004 Aug; 2004 Apr 13. PMID: 15082754
• Yono M, Latifpour J, Takahashi W, Pouresmail M, Afiatpour P, Weiss RM: Age-related changes in the properties of the endothelin receptor system at protein and mRNA levels in the rat vas deferens. J Recept Signal Transduct Res. 2004 Feb. PMID: 15344879
• Hausladen DA, Wheeler MA, Altieri DC, Colberg JW, Weiss RM: Effect of intravesical treatment of transitional cell carcinoma with bacillus Calmette-Guerin and mitomycin C on urinary survivin levels and outcome. J Urol. 2003 Jul. PMID: 12796695
• Sheryka E, Wheeler MA, Hausladen DA, Weiss RM: Urinary interleukin-8 levels are elevated in subjects with transitional cell carcinoma. Urology. 2003 Jul. PMID: 12837459
• Afiatpour P, Latifpour J, Takahashi W, Yono M, Foster HE Jr, Ikeda K, Pouresmail M, Weiss RM: Developmental changes in the functional, biochemical and molecular properties of rat bladder endothelin receptors. Naunyn Schmiedebergs Arch Pharmacol. 2003 May; 2003 Apr 17. PMID: 12700883
• Walsh SA, Weiss RM: Case report: persistent dysuria and a suprapubic mass in a 3-year-old boy. Curr Opin Pediatr. 2002 Oct. PMID: 12352261
• Wheeler MA, Hausladen DA, Yoon JH, Weiss RM: Prostaglandin E2 production and cyclooxygenase-2 induction in human urinary tract infections and bladder cancer. J Urol. 2002 Oct. PMID: 12352459
• Yono M, Takahashi W, Pouresmail M, Johnson DR, Foster HE Jr, Weiss RM, Latifpour J: Quantification of endothelins, their receptors, and endothelin-converting enzyme mRNAs in rat genitourinary tract using real-time RT-PCR. J Pharmacol Toxicol Methods. 2002 Sep-Oct. PMID: 14565565
• Takahashi W, Afiatpour P, Jr Foster HE, Ikeda K, Wada Y, Weiss RM, Latifpour J: The effect of castration on endothelins, their receptors and endothelin converting enzyme in rat prostate. Naunyn Schmiedebergs Arch Pharmacol. 2002 Aug; 2002 May 24. PMID: 12122504
• Sharp JD, Hausladen DA, Maher MG, Wheeler MA, Altieri DC, Weiss RM: Bladder cancer detection with urinary survivin, an inhibitor of apoptosis. Front Biosci. 2002 Feb 1; 2002 Feb 1. PMID: 11815300

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