Education & Training
- Philadelphia. College of Pharm & Sci, Phila, PA BSc 06/1960 Pharmacy
- Philadelphia College of Pharm & Sci, Phila, PA MSc 06/1962 Pharmacology
- University of Pennsylvania, Phila, PA PhD 06/1965 Pharmacology
- University of Pennsylvania, Phila, PA postdoc 06/1966 Pharmacology
- Australian Nat Univ., Canberra, Australia postdoc 06/1967 Neurophysiology
A. Personal Statement
I have over 40 years of research experience in neurophysiologic, neuropharmacologic and neuroanatomical studies of the pelvic viscera. Currently my research focuses on the neural control of the lower urinary tract and the mechanisms underlying neurotransmission at central and peripheral autonomic synapses. My early electrophysiological studies provided the first direct evidence that reflex micturition in animals is activated by small myelinated (Aδ) bladder afferents which trigger a spinobulbospinal pathway passing through relay circuitry in the rostral brainstem. Subsequent experiments revealed that after spinal cord injury (SCI) this reflex is replaced by a spinal micturition reflex activated by capsaicin sensitive unmyelinated (C-fiber) bladder afferents which undergo plasticity and become sensitized in part by the actions of neurotrophic factors released in the bladder and spinal cord of paraplegic animals. I developed methods including axonal tracing in combination with patch clamp recording in dissociated sensory neurons that enabled us to examine the mechanisms of plasticity in identified bladder afferent neurons after SCI and other pathological conditions. In addition I identified properties of bladder epithelial cells that allow these cells to interact with afferent neurons and participate in bladder sensory mechanisms. I have also studied the maturation of bladder reflex pathways during postnatal development and the synaptic modulatory mechanisms in peripheral autonomic ganglia that regulate the transfer of information from the central nervous system to the pelvic visceral organs.
1. de Groat, W.C. and Ryall, R.W. The identification and characteristics of sacral preganglionic parasympathetic neurons. Journal of Physiology, 196:533-577, 1968.
2. de Groat, W.C. and Ryall, R.W. Reflexes to sacral parasympathetic neurons concerned with micturition in the cat. Journal of Physiology (Lond.), 200:87-108, 1969.
3. de Groat, W.C., Nadelhaft, I., Milne, R.J., Booth, A.M., Morgan, C. and Thor, K. Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. Journal of Autonomic Nervous System, 3:135-160, 1981.
4. Yoshimura, N., White, G., Weight, F.F., and de Groat, W.C. Different types of Na+ and A-type K+ currents in dorsal root ganglion neurons innervating the rat urinary bladder. Journal of Physiology, 494: 1-16, 1996.
5. de Groat, W. C. and Yoshimura, N. Afferent Nerve Regulation of Bladder Function in Health and Disease. IN: Pharmacology of Sensory Nerves, Handbook of Experimental Pharmacology, Eds. Canning B. J. and Spina, D., Springer, Heidelberg, Germany, 194: 91-138, 2009. PMC3383010
B. Positions and Honors
Positions and Employment
1967-1968 Visiting Research Fellow, Dept. Physiol., Australian National Univ
1968-1972 Assistant Professor, Dept. of Pharmacology, Univ. Pittsburgh, Pgh,
1972-1977 Associate Professor, Dept. of Pharmacology, Univ. Pittsburgh
1977- 2009 Professor, Dept. of Pharmacology, Univ. Pittsburgh
1978-1980 Acting Chairman, Dept. of Pharmacology, Univ. Pittsburgh
1984-1992 Director, Graduate Studies, Dept. of Pharmacology., Univ. Pittsburgh
1986-1992 Professor (2nd appoint.), Dept. of Neuroscience., Univ. Pittsburgh
2009 Distinguished Professor, Dept. of Pharmacology & Chemical Biology, Univ. Pittsburgh
Other Experience and Professional Memberships
1988-1990 Visiting Scientist, NIH/NIAAA, Rockville, MD
1998 Visiting Scientist, Univ. College London, London, UK
1983-1988 NIH Neurobiology Study Section
2000-2003 Executive Committee of NIH Bladder Research Progress Review Group and Member of Diabetes and Incontinence Subcommittees.
2003-2005 Scientific Advisory Board, Christopher and Dana Reeve Foundation
2008-2009 Faculty of 1000 Biology, Head of Section for the Genito-Urinary and Reproductive Pharmacology
2009 Interdisciplinary Functional Pain Consortium Steering Committee of the International Foundation for Gastrointestinal Disorders.
1966-1968 National Science Foundation Postdoctoral Fellowship
1972-1977 Research Career Development Award, NIH
1974, 78, 80, 83, 88 Student Amer. Med. Assoc. “Golden Apple” Awards for Excellence in Teaching
1990 Univ. Pittsburgh, President’s Distinguished Research Award
1991 DeLourme Distinguished Lecturer, Biennial IC-SCI Conference, Paris
1993 Sir Ludwig Guttman Lecturer, International Congress of Paraplegia, Ghent
1994-1995 Treasurer, Society of Neuroscience
1995 Lifetime Achievement Award, The Urodynamics Society.
1995 G. Heiner Sell Lecturer of the American Spinal Injury Association
1997 Executive Vice President, International Society for Autonomic Neuroscience
1997-2008 Neurophysiology and Neuropharmacology Subcommittees, World Health Organization
(WHO) 1st-4th International Consultations on Urinary Incontinence. Chairman of 1st Subcommittee.
2000-2010 MERIT Award, NIH
2000 Elsevier-JANS Lecturer at the Millennium Congress of the International Society for Autonomic Neuroscience, London
2001 Carl Ludwig Distinguished Lectureship of the American Physiological Society
2000, 01, 02, 03 Excellence in Education Awards from University of Pittsburgh Medical School Classes
2001 Fellow, American Association for the Advancement of Science
2001 National Kidney Foundation Lectureship at the American Academy of Pediatrics Meeting
2001 Dean’s Master Educator Award
2002 Honorary Member of the Japanese Urological Association
2002 University of Pittsburgh Chancellor’s Distinguished Teaching Award
2003 Pharmacia-ASPET Award for Experimental Therapeutics from the American Society for Pharmacology and Experimental Therapeutics
2003 Honorary Member of the American Urological Association
2007 Reeve-Irvine Research Medal for Research in the field of Spinal Cord Injury
2008 President of the 4th World Health Organization International Consultation on Incontinence
2009 State-of-the-Art Lecture at the 39th International Continence Society Meeting
C. Contribution to Science (Selected from over 490 papers and over 89 reviews)
1. We conducted some of the early anatomical studies of the visceral efferent and primary afferent pathways using modern neural tracing techniques.
a. de Groat, W.C., Nadelhaft, I., Morgan, C. and Schauble, T. The central origin of efferent pathways in the carotid sinus nerve of the cat. Science, 205:1017-1018, 1979.
b. Nadelhaft, I., Morgan, C. and de Groat, W.C. Location and morphology of parasympathetic preganglionic neurons in the sacral spinal cord revealed by retrograde axonal transport of horseradish peroxidase. Journal of Comparative Neurology, 193:265-281, 1980.
c. Morgan, C., Nadelhaft, I. and de Groat, W.C. The distribution of visceral primary afferents from the pelvic nerve within Lissauer's tract and the spinal gray matter and its relationship to the sacral parasympathetic nucleus. Journal of Comparative Neurology, 201:415-440, 1981.
d. Thor, K., Morgan, C., Nadelhaft, I., Houston, M. and de Groat, W.C. Organization of afferent and efferent pathways in the pudendal nerve of the female cat. Journal of Comparative Neurology, 288:263-279, 1989.
2. Electrophysiological and pharmacological experiments revealed the integrative function of pelvic ganglionic synapses and the ability of these ganglia to modulate the transmission of information from the spinal cord to the peripheral organs.
a. de Groat, W.C. and Saum, W.R. Adrenergic inhibition in mammalian parasympathetic ganglia. Nature New Biology, 231:188-189, 1971.
b. de Groat, W.C. and Saum, W.R. Sympathetic inhibition of the urinary bladder and of pelvic ganglionic transmission in the cat. Journal of Physiology, 220:297-314, 1972.
c. Saum, W.R. and de Groat, W.C. Parasympathetic ganglia: activation of an adrenergic inhibitory mechanism by cholinomimetic agents. Science, 175:659-661, 1972.
d. de Groat, W.C. and Saum, W.R. Synaptic transmission in parasympathetic ganglia in the urinary bladder of the cat. Journal of Physiology, 256:137-158, 1976.
3. Pharmacological experiments revealed the role of amino acids, monoamines and neuropeptides as neurotransmitters in central and peripheral autonomic pathways.
a. de Groat, W.C. and Ryall, R.W. An excitatory action of 5-hydroxytryptamine on sympathetic preganglionic neurons. Experimental Brain Research, 3:299-305, 1967.
b. de Groat, W.C. The effects of glycine, GABA and strychnine on sacral parasympathetic preganglionic neurons. Brain Research, 18:542-544, 1970. de Groat, W.C.
c. The actions of gamma-aminobutyric acid and related amino acids on mammalian autonomic ganglia. The Journal of Pharmacology and Experimental Therapeutics, 172:384-396, 1970.
d. Kawatani, M., Rutigliano, M. and de Groat, W.C. Depolarization and muscarinic excitation induced in a sympathetic ganglion by vasoactive intestinal polypeptide. Science, 229:879-881, 1985.
4. Neurochemical studies identified neuron-like properties of epithelial cells in visceral organs.
a. Birder, L.A., Apodaca, G., de Groat, W.C., and Kanai, A.J. Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. American Journal of Physiology, 275: F226-F229, 1998.
b. Knight, G.E., Bodin, P., de Groat, W.C., Burnstock, G. ATP is released from epithelium of the guinea pig ureter upon distension. American Journal Physiology- Renal Physiology, 282:F281-F288, 2002.
c. Birder, L.A., Nakamura, Y., Kiss, S., Nealen, M.L., Barrick, S., Kanai, A.J., Wang, E., Ruiz, G., de Groat, W.C., Apodaca, G., Watkins, S., Caterina, M.J. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nature Neuroscience, 5: 856-860, 2002.
d. Kullmann, A., Birder, L.A., Shah, M., and de Groat, W.C. Functional TRP and ASIC-like channels in cultured urothelial cells from the rat. American Journal Physiology- Renal Physiology, 296: F892-F901, 2009. PMC3973644
5. Pharmacological studies identified the mechanisms underlying neuromodulation of lower urinary tract function.
a. Tai, C., Shen, B., Mally, A.D., Zhang, F., Zhao, S., Wang, J Roppolo, J. R., and de Groat, W.C. Inhibition of micturition reflex by activation of somatic afferents in posterior femoral cutaneous nerve. Journal of Physiology (Lond.), 590: 4945-4955, 2012. PMC3487047
b. Matsuta, Y., Mally, A., Zhang, F., Shen, B., Wang, J., Roppolo, J., de Groat, W. C. and Tai, C., Contribution of opioid and metabotropic glutamate receptor mechanisms to inhibition of bladder overactivity by tibial nerve stimulation. American Journal of Physiology - Renal Physiology, 305: R126-133, 2013. PMC3726997
c. Tai, C., Larson, J.A., Ogagan, P.D., Chen, G., Shen, B., Wang, J., Roppolo, J.R. and de Groat W.C. Differential role of opioid receptors in tibial nerve inhibition of nociceptive and non-nociceptive bladder reflexes in cats. American Journalof Physiology- Renal Physiology, 302: F1090-F1097, 2012. PMC3362170
d. Tai, C., Shen, B., Chen, M., Wang, J., Roppolo, J., and de Groat, W.C. Prolonged post-stimulation inhibition of bladder activity induced by tibial nerve stimulation in cats. American Journal of Physiology- Renal Physiology, 300: F385-F392, 2011. PMC3044011