Professional Summary:
Dr. Ruggieri received the Ph.D. degree in Pharmacology from the University of Pennsylvania in 1984. Upon completion of his Ph.D degree he was awarded a New Investigator award (R23) from the NIH and accepted Research Associate then Research Assistant Professor faculty positions at the University of Pennsylvania. He moved to Temple University in 1990 as Research Associate Professor and Director of Urologic Research. Dr. Ruggieri received 21 consecutive years of NIH funding and has recently been awarded two new, 5 year RO1 grants. The fist grant is titled “Bladder, Urethral and Anal Sphincter Reinnervation” and the aims are to determine whether transfer of the genitofemoral (GF) nerve to the anterior vesicle branch of the pelvic nerve by end to end anastomosis reinnervates the internal sphincter smooth muscle as well as the detrusor muscle and determine whether both autonomic ganglia, smooth muscle or both become functionally reinnervated. An additional aim is to determine whether unilateral GF to anterior vesicle nerve transfer provides as much functional reinnervation for bladder emptying as bilateral nerve transfer does. The other grant is titled “Lower Esophageal Antireflux Mechanisms”. One of the aims will test the hypothesis that there is a difference in contractility of the gastric sling/clasp muscle fiber complex between subjects with and without reflux. Funding is also derived from the AstraZeneca corporation to determine the cellular location of the nicotinic receptor subunits present in the human gastric sling/clasp muscle fiber complex by immunohistochemistry and to determine the pharmacologic specificity of the nicotinic receptor mediated relaxation. All studies are in human tissue from whole gastroesophageal specimens obtained from organ transplant donors.
Abstract:
Gastro esophageal reflux disease (GERD) affects at least 40% of the population. Current treatments for GERD do not prevent reflux of gastric contents. Problems associated with GERD include the minor inconveniences of heartburn to the lethal complications of aspirational pneumonia in infancy and esophageal adenocarcinoma in adulthood. Our central hypothesis is that a defect in the gastric clasp/sling muscle fiber complex is the underlying etiology of GERD. Our objectives are to identify receptors on the muscles and the nerves innervating these muscles that are implicated as causing GERD. Our focus is to use this information to develop new pharmacologic treatments targeting these receptors and impacting positively on the public health and health care expenditures. The first aim is to test the hypothesis that GERD patients have different responses of the gastric sling/clasp muscle fiber complex than normal volunteers without GERD and that these responses result in reflux. The second aim is to test the hypothesis that both complete (Nissen) and 270º (Toupet) fundoplication procedures reduce reflux by strengthening the defective sling/clasp muscle fiber complex through tonic muscarinic receptor mediated tension of the gastric smooth muscle in the wrap of the fundoplication. The third aim is to test the hypothesis that there is a difference in contractility of the gastric sling/clasp muscle fiber complex between subjects with and without GERD. We compare the neurotransmitters and receptors responsible for in-vitro contraction and relaxation of smooth muscle strips from whole gastro esophageal specimens obtained from organ transplant donors with and without GERD. We compare responses between the following muscle strips: gastric sling muscle fibers, gastric clasp muscle fibers, lower esophageal circular muscle fibers, mid esophageal circular muscle fibers, and longitudinal esophageal muscle fibers.
Recent publications on this subject you may wish to review:
ACADEMIC:
| 1990-present |
Research Associate Professor, School of Medicine, Temple University Department of Urology, Secondary Appointment, Department of Pharmacology. |
| 2005-present |
Research Associate Professor, College of Engineering, Temple University Department of Computer and Electrical Engineering. |
| 1988-1989 |
Adjunct Assistant Professor of Pharmacology, Philadelphia College of Pharmacy and Science. |
| 1986-1990 |
Research Assistant Professor of Urology, School of Medicine, University of Pennsylvania Division of Urology. |
| 1985-1986 |
Research Associate, School of Medicine, University of Pennsylvania Division of Urology. |
Grant review Committees:
| 1994-2009 |
Ad-hoc reviewer, NHLB, NIDDK, NGMS |
| 2005-2009 |
NIDDK Special Emphasis Panel Loan Repayment Program |
| 1995-2007 |
external reviewer, Veterans Administration Merit Review |
| 2003, 2005, 2006, 2008 |
United States Army Medical Research and Material Command Peer Reviewed Medical Research Program, Chairperson Program on Interstitial Cystitis, NIH George M. O’Brien Center Grant Review |
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2003, 2008, 2009 |
Chair |
Honors and Awards:
| 1983 |
Klingstein Fellow Cold Spring Harbor Symposium “Neurobiology of Human Disease”. |
| 1989, 1993 |
Jack Lapides Essay Contest in Urodynamic and Neurourology Research of the American Urological Association; Bladder Purinergic Receptors, Human Prostate Muscarinic Receptor Subtypes |
| 2004-2007 |
Member of the $1 Million Research Awards Club, Temple University. |
Selected peer-reviewed publications (from 114 publications, 156 abstracts)
Peer Reviewed Publications:
| Ruggieri, M.R. Mechanisms of Disease: role of purinergic signaling in the pathophysiology of bladder dysfunction. Nature Clinical Practice: Urology, 3 (4), 206-215, 2006. |
Ruggieri, M.R. and Braverman, A.S. Regulation of bladder muscarinic receptor subtypes by experimental pathologies. Autonomic & Autocoid Pharmacology, 26, 311-325, 2006. |
Braverman, A.S., LeBed, B., Linder, B.S. and Ruggieri, M.R. M2 mediated contractions of human bladder from organ transplant donors is associated with an up-regulation of urothelial muscarinic receptors. Neurourology and Urodynamics, 26, 63-70, 2007. |
Ruggieri MR, Sr., Braverman AS, D'Andrea, L., McCarthy, J. and Barbe, MF Functional reinnervation of the canine bladder after spinal root transection and immediate somatic nerve transfer. J. Neurotrauma, 25, #3, 214-224, 2008. |
Ruggieri MR, Sr., Braverman AS, D'Andrea, L., Betz, R. and Barbe, MF Functional reinnervation of the canine bladder after spinal root transection and genitofemoral nerve transfer one and three months after denervation. J. Neurotrauma, 25, #4, 398-406, 2008. |
Pontari, M.A. and Ruggieri, M.R. Mechanisms in prostatitis/chronic pelvic pain. J. Urol., 179 (5) Suppl., S61-S67, 2008 (reprinted from Journal of Urology 172 (3): 839-845, 2004). |
Braverman, A.S., Miller, L.S., Vegesna, A.K., Tiwana, M.I., Tallarida, R.J., and Ruggieri, M.R. Quantitation of the contractile response mediated by two receptors: M2 and M3 muscarinic receptor mediated contractions of human gastroesophageal smooth muscle. J. Pharmacol. Exp. Ther., 329:218-224, 2009 Published Online January 6, 2009; doi: 10.1124/jpet.108.148106. |
Pontari, M.A., Mohammed, F., Lebovitch, S., Moonat, S., Lebed, B., Ruggieri, M.R., Sr. and Faro, S. Brain functional magnetic resonance imaging (fMRI) during bladder filling and emptying in patients before and after treatment with anticholinergic medication. J. Urol., in press, 2010. |
Vegesna, A.K., Braverman, A.S., Tallarida, R.J., Miller, L.S., Tiwana, M.I., Khayam, U., and Ruggieri, M.R., Sr. Comparison of Human and Porcine Gastric Clasp and Sling Fiber Contraction by M2 and M3 Muscarinic Receptors. Am. J. Physiol., February 4, 2010. doi:10.1152, in press, 2010. |
Ruggieri, M.R., Sr. Cannabinoids: Potential targets for bladder dysfunction. Handbook Exp. Pharmacol. In press, 2010. |
Selected Abstracts:
| Braverman, A.S., Kreitman, Y., and Ruggieri, M.R. The effect of knock out of urothelial M3 receptors on mouse bladder contractility. American Urological Association, San Francisco, 2010. |
| Vegesna, A., Braverman, A.S., Miller, L., Tiwana, M., Miller, E. and Ruggieri, M.R. Gastric clasp and lower esophageal circular muscle fibers from GERD patients with Barrett’s esophagitis have a decreased contractile response to cholinergic stimulation. Accepted for presentation Digestive Diseases Week, 2010. |
| Ruggieri, M.R., Vegesna, A.K., Braverman, A.S., Tiwana, M., Gotimukkla, S. and Miller, L. Pharmacologic specificity of nicotinic receptor mediated relaxation of muscarinic receptor pre-contracted human gastric clasp and sling muscle fibers. Accepted for presentation Digestive Diseases Week, 2010. |
| Barbe, M.F., Braverman, A.S., Vegesna, A. Miller, L. and Ruggieri, M.R. Immunofluorescent localization of nicotinic receptor subunits to specific cell types in human clasp fibers. Accepted for presentation Digestive Diseases Week, 2010. |
| Vegesna, A., Tiwana, M., Braverman, A.S., Miller, L., and Ruggieri, M.R. Contractile response of porcine esophageal muscularis mucosa to carbachol. Accepted for presentation Digestive Diseases Week, 2010. |
Research Support - Ongoing Research Support:
As Principal Investigator:
| Animal Models for Investigation of Urothelial Muscarinic Receptor Function.2007 Pfizer OAB-LUTS Competitive Grants Program |
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Total costs, 2 years: $75,000 |
2007-2009 |
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| Feasibility of Somatic Nerve Transfer for Urinary Bladder Reinnervation: A Prelude for Restoration of Bladder Emptying with Functional Electrical Stimulation. Shriner’s Hospital for Children project number 8510 |
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Total costs, 2 years: $440,490 |
2008-2009 |
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| Role of M2 and M3 Receptor Internalization in Human Bladder Sensitivity to Cholinergic Stimulation. 2009 Pfizer OAB-LUTS Competitive Grants Program |
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Total costs, 2 years: $75,000 |
2009-2011 |
As Co-Principal Investigator:
| Urothelial Derived Inhibitory Factor. 2008 Pfizer OAB-LUTS Competitive Grants Program PI: Alan S. Braverman, Ph.D. |
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Total costs, 2 years: $75,000 |
2008-2010 |
Completed Research Support (Selected, as Principal Investigator):
| Urinary Bladder Muscarinic Receptor Subtypes DK43333-04 |
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Total: $997,776 |
1991-2006 |
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| Interstitial Cystitis: Human and Animal Studies DK39086 |
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Total: $4693,375 |
1993-1996 |
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| Antibacterial Defense Factors of Urinary Bladder Mucosa DK42890 |
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Total: $501,975 |
1991-1996 |
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| Experimental cystoplasty: In-vitro and in-vivo studies DK40579 |
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Total $434,508 |
1992-1996 |
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| Purinergic innervation of the rabbit urinary bladder R23 NS22087 |
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Total: $156,327 |
1985-1989 |
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