Robert M. Weiss
MD, FACS, FAAP
Donald Guthrie Professor of Urology
Research & Publications
Biography
News
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.
Coauthors
Research Interests
Urinary Bladder Neoplasms; Pharmacology; Urology; Signal Transduction
Selected Publications
- Anaerobic urinary infections: Bacteroides fragilis bacteremia from the urinary tract.Bagley D, Kliger A, Weiss RM. Anaerobic urinary infections: Bacteroides fragilis bacteremia from the urinary tract. The Journal Of Urology 1980, 124:160-1.
- Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin.Carpenter TO, Imperato-McGinley J, Boulware SD, Weiss RM, Shackleton C, Griffin JE, Wilson JD. Variable expression of 5 alpha-reductase deficiency: presentation with male phenotype in a child of Greek origin. The Journal Of Clinical Endocrinology And Metabolism 1990, 71:318-22.
- Effect of experimental diabetes on rat prostate endothelin receptors.Saito M, Nishi K, Foster HE, Weiss RM, Latifpour J. Effect of experimental diabetes on rat prostate endothelin receptors. European Journal Of Pharmacology 1996, 310:197-200.
- Urinary nitric oxide synthase activity and cyclic GMP levels are decreased with interstitial cystitis and increased with urinary tract infections.Smith SD, Wheeler MA, Foster HE, Weiss RM. Urinary nitric oxide synthase activity and cyclic GMP levels are decreased with interstitial cystitis and increased with urinary tract infections. The Journal Of Urology 1996, 155:1432-5.
- Nitric oxide synthase induction with renal transplant rejection or infection.Smith SD, Wheeler MA, Zhang R, Weiss ED, Lorber MI, Sessa WC, Weiss RM. Nitric oxide synthase induction with renal transplant rejection or infection. Kidney International 1996, 50:2088-93.
- Bacterial infection induces nitric oxide synthase in human neutrophils.Wheeler MA, Smith SD, García-Cardeña G, Nathan CF, Weiss RM, Sessa WC. Bacterial infection induces nitric oxide synthase in human neutrophils. The Journal Of Clinical Investigation 1997, 99:110-6.
- Pseudoexstrophy of the bladder: case report and literature review.Swana HS, Gallagher PG, Weiss RM. Pseudoexstrophy of the bladder: case report and literature review. Journal Of Pediatric Surgery 1997, 32:1480-1.
- Bladder instillation and intraperitoneal injection of Escherichia coli lipopolysaccharide up-regulate cytokines and iNOS in rat urinary bladder.Olsson LE, Wheeler MA, Sessa WC, Weiss RM. Bladder instillation and intraperitoneal injection of Escherichia coli lipopolysaccharide up-regulate cytokines and iNOS in rat urinary bladder. The Journal Of Pharmacology And Experimental Therapeutics 1998, 284:1203-8.
- Gene expression, localization, and pharmacological characterization of endothelin receptors in diabetic rat bladder dome.Saito M, Wada Y, Ikeda K, Wang Z, Smith SD, Foster HE, Nishi K, Weiss RM, Latifpour J. Gene expression, localization, and pharmacological characterization of endothelin receptors in diabetic rat bladder dome. European Journal Of Pharmacology 2000, 387:253-63.
- Age-related changes in contractile responses of rabbit lower urinary tract to endothelin.Wada Y, Latifpour J, Sanematsu H, Afiatpour P, Wang Z, Saito M, Nishi K, Weiss RM. Age-related changes in contractile responses of rabbit lower urinary tract to endothelin. The Journal Of Urology 2000, 164:806-13.
- Urine detection of survivin and diagnosis of bladder cancer.Smith SD, Wheeler MA, Plescia J, Colberg JW, Weiss RM, Altieri DC. Urine detection of survivin and diagnosis of bladder cancer. JAMA 2001, 285:324-8.
- Regulatory effect of experimental diabetes on the expression of endothelin receptor subtypes and their gene transcripts in the rat adrenal gland.Ikeda K, Wada Y, Sanematsu H, Foster HE, Shin D, Weiss RM, Latifpour J. Regulatory effect of experimental diabetes on the expression of endothelin receptor subtypes and their gene transcripts in the rat adrenal gland. The Journal Of Endocrinology 2001, 168:163-75.
- Case report: persistent dysuria and a suprapubic mass in a 3-year-old boy.Walsh SA, Weiss RM. Case report: persistent dysuria and a suprapubic mass in a 3-year-old boy. Current Opinion In Pediatrics 2002, 14:647-8.
- Quantification of endothelins, their receptors, and endothelin-converting enzyme mRNAs in rat genitourinary tract using real-time RT-PCR.Yono M, Takahashi W, Pouresmail M, Johnson DR, Foster HE, Weiss RM, Latifpour J. Quantification of endothelins, their receptors, and endothelin-converting enzyme mRNAs in rat genitourinary tract using real-time RT-PCR. Journal Of Pharmacological And Toxicological Methods 2002, 48:87-95.
- Bladder cancer detection with urinary survivin, an inhibitor of apoptosis.Sharp JD, Hausladen DA, Maher MG, Wheeler MA, Altieri DC, Weiss RM. Bladder cancer detection with urinary survivin, an inhibitor of apoptosis. Frontiers In Bioscience : A Journal And Virtual Library 2002, 7:e36-41.
- Prognostic value of urodynamic testing in myelodysplastic patients. 1981.McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. 1981. The Journal Of Urology 2002, 167:1049-53; discussion 1054.
- The effect of castration on endothelins, their receptors and endothelin converting enzyme in rat prostate.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-Schmiedeberg's Archives Of Pharmacology 2002, 366:166-76.
- Prostaglandin E2 production and cyclooxygenase-2 induction in human urinary tract infections and bladder cancer.Wheeler MA, Hausladen DA, Yoon JH, Weiss RM. Prostaglandin E2 production and cyclooxygenase-2 induction in human urinary tract infections and bladder cancer. The Journal Of Urology 2002, 168:1568-73.
- Effect of intravesical treatment of transitional cell carcinoma with bacillus Calmette-Guerin and mitomycin C on urinary survivin levels and outcome.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. The Journal Of Urology 2003, 170:230-4.
- Developmental changes in the functional, biochemical and molecular properties of rat bladder endothelin receptors.Afiatpour P, Latifpour J, Takahashi W, Yono M, Foster HE, Ikeda K, Pouresmail M, Weiss RM. Developmental changes in the functional, biochemical and molecular properties of rat bladder endothelin receptors. Naunyn-Schmiedeberg's Archives Of Pharmacology 2003, 367:462-72.
- Urinary interleukin-8 levels are elevated in subjects with transitional cell carcinoma.Sheryka E, Wheeler MA, Hausladen DA, Weiss RM. Urinary interleukin-8 levels are elevated in subjects with transitional cell carcinoma. Urology 2003, 62:162-6.
- Rapid up-regulation of endothelial nitric-oxide synthase in a mouse model of Escherichia coli lipopolysaccharide-induced bladder inflammation.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. The Journal Of Pharmacology And Experimental Therapeutics 2004, 310:452-8.
- Age-related changes in the properties of the endothelin receptor system at protein and mRNA levels in the rat vas deferens.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. Journal Of Receptor And Signal Transduction Research 2004, 24:53-66.
- A survivin gene signature predicts aggressive tumor behavior.Salz W, Eisenberg D, Plescia J, Garlick DS, Weiss RM, Wu XR, Sun TT, Altieri DC. A survivin gene signature predicts aggressive tumor behavior. Cancer Research 2005, 65:3531-4.
- Regulation of cyclic nucleotides in the urinary tract.Wheeler MA, Ayyagari RR, Wheeler GL, Weiss RM. Regulation of cyclic nucleotides in the urinary tract. Journal Of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi 2005, 41:1-21.
- Clinical and histological significance of the testicular remnant found on inguinal exploration after diagnostic laparoscopy in the absence of a patent processus vaginalis.Renzulli JF, 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. The Journal Of Urology 2005, 174:1584-6; discussion 1586.
- Effect of insulin treatment on tissue size of the genitourinary tract in BB rats with spontaneously developed and streptozotocin-induced diabetes.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-Schmiedeberg's Archives Of Pharmacology 2005, 372:251-5.
- Age related changes in the functional, biochemical and molecular properties of alpha1-adrenoceptors in the rat genitourinary tract.Yono M, Foster HE, Weiss RM, Latifpour J. Age related changes in the functional, biochemical and molecular properties of alpha1-adrenoceptors in the rat genitourinary tract. The Journal Of Urology 2006, 176:1214-9.
- Pacemaker activity in the upper urinary tract.Weiss RM, Tamarkin FJ, Wheeler MA. Pacemaker activity in the upper urinary tract. Journal Of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi 2006, 42:103-15.
- A role for Akt in the rapid regulation of inflammatory and apoptotic pathways in mouse bladder.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-Schmiedeberg's Archives Of Pharmacology 2006, 373:349-59.
- 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.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 Investigation 2007, 25:678-84.
- Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra.Wada Y, Takahashi W, Latifpour J, Yamada G, Kai N, Honda J, Nakanishi J, Weiss RM. Regional differences in the functional and biochemical properties of endothelin receptor subtypes in the rabbit prostatic urethra. BJU International 2007, 100:430-7.
- Initial experience with 3% sodium tetradecyl sulfate foam and fibered coils for management of adolescent varicocele.Reiner E, Pollak JS, Henderson KJ, Weiss RM, White RI. Initial experience with 3% sodium tetradecyl sulfate foam and fibered coils for management of adolescent varicocele. Journal Of Vascular And Interventional Radiology : JVIR 2008, 19:207-10.
- Differential effects of diabetes induced by streptozotocin and that develops spontaneously on prostate growth in Bio Breeding (BB) rats.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 Sciences 2008, 83:192-7.
- Prostate expression of endothelins and their receptors in rat growth.Wada Y, Takahashi W, Latifpour J, Weiss RM, Matsumoto K, Matsui K, Yamada G, Imamura T. Prostate expression of endothelins and their receptors in rat growth. Reproduction, Fertility, And Development 2008, 20:750-9.
- 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.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 International 2011, 107:1154-61.
- Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer.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 : Nanotechnology, Biology, And Medicine 2013, 9:1124-34.
- Brg1 determines urothelial cell fate during ureter development.Weiss RM, Guo S, Shan A, Shi H, Romano RA, Sinha S, Cantley LG, Guo JK. Brg1 determines urothelial cell fate during ureter development. Journal Of The American Society Of Nephrology : JASN 2013, 24:618-26.
- Surface-modified nanoparticles enhance transurothelial penetration and delivery of survivin siRNA in treating bladder cancer.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. Molecular Cancer Therapeutics 2014, 13:71-81.
- Legends in Urology.Weiss RM. Legends in Urology. The Canadian Journal Of Urology 2018, 25:9296-9299.
- Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target.Martin DT, Shen H, Steinbach-Rankins JM, Zhu X, Johnson KK, Syed J, Saltzman WM, Weiss RM. Glycoprotein-130 Expression Is Associated with Aggressive Bladder Cancer and Is a Potential Therapeutic Target. Molecular Cancer Therapeutics 2019, 18:413-420.
- Synergistic inhibition of GP130 and ERK signaling blocks chemoresistant bladder cancer cell growth.Li X, He S, Tian Y, Weiss RM, Martin DT. Synergistic inhibition of GP130 and ERK signaling blocks chemoresistant bladder cancer cell growth. Cellular Signalling 2019, 63:109381.
- Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis.He S, Li G, Schätzlein AG, Humphrey PA, Weiss RM, Uchegbu IF, Martin DT. Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis. Cellular Signalling 2021, 81:109931.
- Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles.Li G, He S, Schätzlein AG, Weiss RM, Martin DT, Uchegbu IF. Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles. Journal Of Controlled Release : Official Journal Of The Controlled Release Society 2021, 332:210-224.
- Genome-wide association analysis reveals regulation of at-risk loci by DNA methylation in prostate cancer.Liu Q, Liu G, Martin DT, Xing YT, Weiss RM, Qi J, Kang J. Genome-wide association analysis reveals regulation of at-risk loci by DNA methylation in prostate cancer. Asian Journal Of Andrology 2021, 23:472-478.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Children's Health; Diseases of the Kidney & Urinary Tract | OnabotulinumtoxinA for the Treatment of Urinary Incontinence Due to Overactive Bladder in Pediatric Patients |