William D. Willis, M.D., Ph.D., Professor Emeritus

  • Affiliations: Department of Neuroscience & Cell Biology
  • Route: 1069, Medical Research Building (MRB)
  • Tel: (409) 747-2169
  • Fax: (409) 772-4687

William D. Willis, M.D., Ph.D.

General Information

Dr. Willis joined the staff of the Marine Biomedical Institute in 1970 as Chief of the Division of Comparative Neurobiology. From 1978-2003, he served as Director of the Institute. From 1986-2003, he was appointed Professor and Chairman of the Department of Anatomy & Neurosciences. He was honored as Cecil H. and Ida M. Green Distinguished University Chair in 1994-2003 and Cecil H. and Ida M. Green Distinguished Chair in Neuroscience from 2004 to the present. His research interest is the structure and function of the vertebrate spinal cord and brain stem.

A native of Dallas, Dr. Willis obtained his B.S. and B.A. degrees from Texas A. & M. University in 1956. In 1960, he received his M.D. degree from the University of Texas Southwestern Medical School at Dallas. Dr. Willis then earned his Ph.D. degree in 1963 from the Australian National University under the supervision of Sir John C. Eccles. Thereafter, he worked in Italy as an NINDS postdoctoral research fellow under Professor Giuseppi Moruzzi in the Institute of Physiology, University of Pisa. In 1963, Dr. Willis returned to the University of Texas Southwestern Medical School as an Assistant Professor of Anatomy. He became Professor and Chairman of Anatomy in 1964 and Professor of Physiology in 1969.

Dr. Willis has been President of the Society for Neuroscience (1984-5), the Association of Neuroscience Departments and Programs (1982-3), the Cajal Club (1982-3) and the American Pain Society (1982-3). He has also been on the Executive Committee of the American Association of Anatomists (1982-6) and the Council of the International Association for the Study of Pain (1984-90). Dr. Willis has been on several NIH review boards, including the Neurology B Study Section (1968-72, Chairman 1970-72), Neurological Disorders Program Project Review Committee (1972-76), National Advisory Neurological and Communicative Disorders and Stroke Council (1987-90) and NINDS Training Grant and Career Development Review Committee (1994-98). He has been appointed to a number of editorial boards and served as Chief Editor of the Journal of Neurophysiology (1978-83) and later Editor-in-Chief of the Journal of Neuroscience (1993-4). He has also served on the Physiology Test Committee (Chairman, 1986-8), Multidisciplinary Part I Task Force (1989-90), Step 1 Committee (1992-4) and Neuroscience Task Force (1994-98) of the National Board of Medical Examiners.

Dr. Willis has supervised the research programs of 24 Ph.D. students, 6 M.A. students and 64 postdoctoral fellows and visiting scientists. Recognition for the teaching efforts of Dr. Willis have included the Distinguished Teaching Award by the Freshman Class, University of Texas Southwestern Medical School (1970), the Distinguished Teaching Award of the Graduate Student Organization, UTMB (1977 and 1999), the Dean of Medicine's Teacher of the Year Award, UTMB (1978), the Alumni Appreciation Award for Excellence in Teaching (1998), and the Jimmy Doyle Dickens Memorial Faculty Award (1999). In 2008, he was made a Distinguished Teaching Professor in the Academy of Master Teachers and a Marie Hall Scholar; the Academy of Master Teachers gave him the 2008 Lifetime Achievement Award for Contributions to the Educational Missions of the GSBS.

Honors for research include the John Sinclair Award, UTMB (1978), the Jacob K. Javits Award by NINDS (1985-92), the Frederick W.L. Kerr Memorial Award by the American Pain Society (1986), and the Bristol-Myers Squibb Award for Distinguished Achievement in Pain Research (1993). Dr. Willis has also received the Nicholas and Katherine Leone Award for Administrative Excellence (1986). Dr. Willis became the first ever recipient of the Purdue Prize for Pain Research at the Spring Pain Research Conference April 26, 2002. This award recognizes outstanding contributions to pain research.

In 2002, the Institute for Scientific Information named Dr. Willis as one of the world’s most highly cited authors (top 0.5% of all publishing authors). In 2003 in Prague, he was presented the J.E. Purkinje Honorary Medal for Merit in the Biological Sciences by Dr. Helena Illnerovά, President of the Academy of Sciences of the Czech Republic. In 2005, he was given the Distinguished Faculty Research Award of the GSBS at UTMB.

 

Research Interests

The emphasis of work in the laboratory of Dr. Willis is on pain mechanisms. The basic goals are to learn how nociceptive information is signaled by the spinal cord to the brain and how to disrupt nociception. Behavioral responses in a rodent model to innocuous and noxious mechanical stimuli and to thermal stimuli provide evidence for the development of allodynia and hyperalgesia following a strong stimulus, such as intradermal injection of capsaicin or visceral inflammation. Parallel experiments are done in which electrophysiological recordings are made from nociceptive neurons in the spinal cord dorsal horn before and after intense stimulation. Synaptic receptor agonists/antagonists or signal transduction pathway activators/inhibitors are administered intrathecally or by microdialysis (to restrict drug action to the spinal cord). The effects of these agents provide evidence for the neurotransmitters and signaling cascades that are involved in the central sensitization of spinal cord neurons, leading to allodynia and hyperalgesia. Further evidence is provided by Western blots and immunohistochemistry. Identification of spinothalamic tract cells or postsynaptic column neurons is done by retrograde labeling using a tracer that is injected into the thalamus or into the dorsal column nuclei. The laboratory has also been engaged in collaborative studies 1) on a visceral pain pathway in the dorsal columns (with K.N. Westlund, E.D. Al-Chaer, and H.J. Nauta); 2) the role of dorsal root reflexes in neurogenic inflammation (with K.N. Westlund and with Q. Lin); 3) central sensitization of dorsal horn neurons in spinal cord injury (with C.E. Hulsebosch); and 4) several studies with faculty from other countries (R.F. Schmidt, Germany; J. Bagust, United Kingdom; Y. Feng, China; J. Palecek and V. Paleckova, Czech Republic; M. Tsuruoka, Japan; T. Ushida, Japan; Wang, J., China; H.Q. Zhang, Hong Kong), as well as with a number of pre- and postdoctoral trainees from this country and abroad.

Publications

Peer-reviewed Publications

Zhang, H.Q., Rong, P.J., Zhang, S.P., Al Chaer, E.D. and Willis, W.D. Noxious visceral inputs enhance cutaneous tactile response in rat thalamus. Neurosci. Lett. 336:109-0112, 2003.

Palecek, J., Paleckova, V. and Willis, W.D. Postsynaptic dorsal column neurons express NK1 receptors following colon inflammation. Neuroscience 116:565-572, 2003.

Feng, Y., Cui, M. and Willis, W.D. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology 98:729-733, 2003.

Lin, Q., Zou, X., Fang, L. and Willis, W.D. Sympathetic modulation of acute cutaneous flare induced by intradermal injection of capsaicin in anesthetized rats. J. Neurophysiol. 89:853-861, 2003.

Hains, B.C., Willis, W.D. and Hulsebosch, C.E. Serotonin receptors 5-HT1A and 5-HT3 reduce hyperexcitability of dorsal horn neurons after chronic spinal cord hemisection injury in rat. Exp. Brain Res. 149:174-186, 2003.

Hains, B.C., Johnson, K.M., Eaton, M.J., Willis, W.D. and Hulsebosch, C.E. Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat. Neuroscience 116:1097-1110, 2003.

Tsuruoka, M., Arai, Y.C., Nomura, H., Matsutani, K. and Willis, W.D. Unilateral hindpaw inflammation induces bilateral activation of the locus coeruleus and the nucleus subcoeruleus in the rat. Brain Res. Bull. 61:117-123, 2003.

Palecek, J., Paleckova, V. and Willis, W.D. Fos expression in spinothalamic and postsynaptic dorsal column neurons following noxious visceral and cutaneous stimuli. Pain 14: 249-257, 2003.

Sun, R.Q., Lawand, N. and Willis, W.D. The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin. Pain 104: 201-208, 2003.

Hains, B.C., Willis, W.D. and Hulsebosch, C.E. Temporal plasticity of dorsal horn somatosensory neurons after acute and chronic spinal cord hemisection in rat. Brain Res. 970:238-241, 2003.

Palecek, J. and Willis, W.D. The dorsal column pathway facilitates visceral responses to colorectal distention after colon inflammation in rats. Pain 104L501-507, 2003.

Feng, Y., Lai, M. and Willis, W.D. Effects of anticonvulsant gabapentin on visceral nociception and its relationship with amino acid neurotransmitters released from spinal cord Beijing Da Xue Xue Bao 35:307-310, 2003 (in Chinese).

Fang, L., Wu, J.m, Lin, Q. and Willis, W.D. Protein kinases regulate the phosphorylation of the GluR1 subunit of AMPA receptors of spinal cord in rats following noxious stimulation. Mol. Brain Res. 118:160-165, 2003.

Fang, L., Wu, J., Zhang, X., Lin, Q. and Willis, W.D. Increased phosphorylation of the GluR1 subunit of spinal cord AMPA receptor in rats following intradermal injection of capsaicin. Neuroscience 122:237-245, 2003.

Zhang, X., Wu, J., Fang, L. and Willis, W.D. The effects of protein phosphatase inhibitors on nociceptive behavioral responses of rats following intradermal injection of capsaicin. Pain 106::443-451, 2003. 2003

Lin, Q., Zou, X., Ren, Y., Wang, J., Fang, L. and Willis, W.D. Involvement of peripheral neuropeptide Y receptors in sympathetic modulation of acute cutaneous flare induced by intradermal capsaicin. Neuroscience 123:337-347, 2004.

Tu, Y., Sun, R.Q. and Willis, W.D. Effects of intrathecal injections of melatonin analogs on capsaicin-induced secondary mechanical allodynia and hyperalgesia in rats. Pain 109:340-350, 2004.

Singh, P., Cobb, S., Rengifo-Cam, W., Deng, X., Willis, W. and Li, Q. Locomotor activity and behavior of mutant mice deleted for gastrin gene expression. J. Physiol. Pharmacol. 55:269-278, 2004.

Sun, R.Q., Lawand, N.B. and Willis, W.D. Role of calcitonin gene-related peptide in the sensitization of dorsal horn neurons to mechanical stimulation after intradermal injection of capsaicin. J. Neurophysiol. 92:320-326, 2004.

Palecek, J., Neugebauer, V., Carlton, S.M., Iyengar, S. and Willis, W.D. The effect of a kainate GluR5 receptor antagonist on responses of spinopthalamic tract neurons in a model of peripheral neuropathy in primates. Pain 111:151-161, 2004.

Zou, X., Lin, Q. and Willis, W.D. Effect of protein kinase C blockade on phosphorylation of NR1in dorsal horn and spinothalamic tract cells caused by intradermal capsaicin injection in rats. Brain Res. 1020:95-105, 2004.

Wang, J., Ren, Y., Zou, X., Fang, L., Willis, W.D. and Lin, Q. Sympathetic influence of capsaicin-evoked enhancement of dorsal root reflexes in rats. J. Neurophysiol, 92: 2017-2026, 2004. 

Lawand, N.B., Reddig, W.J., Cashin, A.E., Westlund, K.N. and Willis, W.D. NMDA receptors and associated signaling pathways: a role in knee joint blood flow regulation. Eur. J. Pharmacol. 499:155-161, 2004.

Fang, L., Wu, J., Zhang, X., Lin, Q. and Willis, W.D. Calcium/calmodulin dependent protein kinase II regulates the phosphorylation of cyclic AMP-responsive element-binding protein of spinal cord in rats following noxious stimulation. Neuroscience Letters, 374:1-4, 2005.

Hoogerwerf, W., Gondesen, K.J., Xiao, S-Y., Winston, J.H., Willis, W.D. and Pasricha, J. The role of mast cells in the pathogenesis of pain in chronic pancreatitis. BMC Gastroenterology 5:8, 2005.

Bird, G.C., Lash, L.L., Heong, S.H., Zou, X., Willis, W.D. and Neugebauer, V. Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in amygdala neurons. Journal of Physiology, 564.3:907-921, 2005.

Ren, Y., Zou, X., Fang, L., Willis, W.D. and Lin, Q. Sympathetic modulation of activity in Aδ and C-primary nociceptive afferents after intradermal injection of capsaicin in rats. J. Neurophysiol., 93:365-377, 2005.

Zhang, X., Wu, J., Lei, Y., Fang, L. and Willis, W.D. Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following intradermal injection of capsaicin, Mol. Brain Res. 138:264-272, 2005.

Palecek J and Willis WD. Responses of neurons in the rat ventral posterior lateral thalamic nucleus to noxious visceral and cutaneous stimuli. Thalamus and Related Systems 3: 25-32, 2005.

Sun RQ, Tu YJ, Yan, JY and Willis WD. Activation of protein kinase B/Akt signaling pathway contributes to mechanical hypersensitivity induced by capsaicin. Pain 120:86-96, 2006.

Valencia de Ita, S, Lawand, NB, Lin, Q, Castañeda-Hernandez, G and Willis WD. Role of the Na+-K+-2Cl- cotransporter in the development of capsaicin-induced neurogenic inflammation. J. Neurophysiol. 95: 3553-3561, 2006.

Zhang, X., Wu, J., Lei, Y., Fang, L. and Willis, W.D. Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin. Molecular Pain 2:9-20, 2006.

Yan JY, Sun RQ, Hughes MG, McAdoo DJ and Willis WD. Intradermal injection of capsaicin induces acute substance P release from rat spinal cord dorsal horn. Neurosci. Lett. 410:183-186, 2006.

Bird GC, Han JS, Fu Y, Adwanikar H, Willis WD and Neugebauer V. Pain-related synaptic plasticity in spinal dorsal horn neurons: role of CGRP. Mol. Pain 2:31, 2006.

Zhang X, Wu J, Fang L and Willis WD. The effects of protein phosphatase inhibitors on the duration of central sensitization of rat dorsal horn neurons following injection of capsaicin. Mol. Pain 2:23, 2006.

Adwanikar H, Ji G, Li W, Doods H, Willis WD and Neugebauer V. Spinal CGRP1 receptors contribute to supraspinally organized pain behavior and pain-related sensitization of amygdale neurons. Pain 132: 53-66, 2007.

Sun RQ, Yan J and Willis WD. Activation of protein kinase B/Akt in the periphery contributed to pain behavior induced by capsaicin in rats. Neurosci. 144:286-294, 2007.

Recent Chapters, Edited Volumes, Monographs, Reviews

Willis WD Dorsal root potentials and dorsal root reflexes: a double-edged swrod. Exp. Brain Res. 124: 395-421, 1999.

Willis WD, Al-Chaer ED, Quast MJ and Westlund KN. A visceral pain pathway in the dorsal column of the spinal cord. In: The Neurobiology of Pain, NAS Colloquium, Irvine, CA, PNAS USA 96:7675-7679, 1999.

Willis WD, Zhang, X, Honda, CN and Giesler, GJ. A critical review of the role of the proposed VMpo nucleus in pain. J. Pain 3:79-94, 2002.

Willis WD Long-term potentiation in spinothalamic neurons. Brain Res. Rev. 40:202-214, 2002.

Willis WD Possible mechanisms of central neuropathic pain. In: Spinal Cord Injury Pain: Assessment, Mechanisms and Management. Yezierski RP and Burchiel, KJ (eds.), pp. 85-115, IASP Press, Seattle, 2002.

Chen J, Chen ACN, Han JS and Willis WD. Experimental pathological pain: from molecules to brain functions. Science Press, Beijing, 2003.

Willis WD. Thalamo-cortical system of nociception in animals. In: Chen et al., pp. 165-196, 2003.

Saab CY and Willis WD. The cerebellum: organization, functions and its role in nociception. Brain Res. Rev. 42:85-95. 2003.

Willis WD. Retrograde signaling in the nervous system: dorsal root reflexes. In: Handbook of cell signaling. Vol. 3, RA Bradshaw and EA Dennis, editors-in-chief, pp. 607-614, Academic Press, San Diego 2003.

Haevner JE and Willis WD. Pain pathways: anatomy and physiology. In: Pain medicine: a comprehensive review, 2nd edition, P.P. Raj (editor), pp. 10-15, Mosby, St. Louis, 2003.

Willis WD, Section II, The Nervous System. In: Physiology, RM Berne, MN Levy, MBM Koepper and BA Stanton (editors), 5th edition, pp. 79-220, Mosby, St. Louis, 2004.

Willis WD and Coggeshall RE. Sensory mechanisms of the spinal cord. 3rd edition, 2 volumes, Kluwer Academic/Plenum Publishers, New York, 950 pp., 2004.

Willis WD and Westlund KN. Pain System. In: The Human Nervous System, 2nd ed., Paxinos G and Mai JK (eds.), Elsevier Academic Press, San Diego, pp. 1125-1170, 2004.

Willis WD, Westlund KN and Carlton SM. Pain System. In: The Rat Nervous System, 3rd ed., Paxinos G (ed.), Elsevier, Amsterdam, pp. 853-890, 2004.

Willis WD. Central sensitization of spinothalamic tract cells is a spinal cord form of long-term potentiation. In: Hyperalgesia: Molecular Mechanisms and Clinical Implications. Progess in Pain Research and Management, Vol. 30, Brune K and Handwerker HO (eds.) IASP Press, Seattle, pp. 181-199, 2004.

Nauta HJW, Westlund KN and Willis WD. Midline myelotomy. In: Surgical Management of Pain. Burchiel, K.J. (ed.). Thieme Medical Publishers, Inc., New York, pp. 714-731, 2002.

Willis, WD John Eccles’ studies of spinal cord presynaptic inhibition. Prog. in Neurobiol., 78: 189-214, 2006.

Willis, WD The somatosensory system, with emphasis on structures important for pain. Brain Res. Rev., Special Issue on Golgi and Cajal, 55: 297-313, 2007.