Pediatric Pharmacology Research Unit

Michael T. Williams, PhD

Appointment

Associate Professor, University of Cincinnati College of Medicine

Email

michael.williams@cchmc.org

Phone

513-636-4222

Fax

513-636-1888

Credentials

AA: Psychology, Belleville Area College
BS: Psychology, Wright State University
PhD: Biomedical Sciences, Wright State University
Post-doctoral Fellow: Psychonueroimmunology, Ohio State University
Post-doctoral Fellow: Teratology, Children's Hospital Research Foundation

Position History

Associate Professor: Neurology, Cincinnati Children's Research Foundation, September 2006-present
Associate Program Director: Cincinnati Children's Research Foundation, November 2004-present
Faculty Member: University of Cincinnati graduate program, Molecular Developmental Biology, October 2002-present
Faculty Member: University of Cincinnati graduate program, Neuroscience, July 2001-present
Assistant Professor: Neurology, Cincinnati Children's Research Foundation, September 2003-August 2006
Instructor: Pharmacology Research Center, Cincinnati Children's Research Foundation, December 2000-2003
Adjunct Instructor: Psychology, Sinclair Community College, September 2000-2002
Adjunct Assistant Professor: Psychology, Wright State University, September 1997-June 2000

Awards and Honors

Pediatric Research Loan Repayment Program Recipient July 2006-2007, NIH
Pediatric Research Loan Repayment Program Recipient July 2004-2006, NIH
Pediatric Research Loan Repayment Program Recipient July 2002-2004, NIH
Post-doctoral Travel Fellowship to attend International Behavioral Neuroscience Society meeting, June 1999
Travel award to attend Midwest Teratology Association, May 1996
Omnitech Travel Fellowship to attend Society of Neuroscience, November 1995
Travel Fellowship to attend International Behavioral Neuroscience Society, April 1993
Graduated (B.S.), Magna Cum Laude, Wright State University, December 1990
Outstanding Achievement in Psychology, Belleville Area College, May 1987

Research Grants and Contracts

Effects of lead, maganese and stress during development. Principal Investigator. National Institute of Health: National Institute of Environmental Health Sciences, Sep 2006- June 2011. #R01 ES015689-01.

Effects of neonatal MDMA on brain and behavior. Co-investigator. National Institute of Health: National Institute on Drug Abuse, Apr 2006- Mar 2011. #R01 DA021394.

Developmental effects of methanphetamine-like stimulants. Co-investigator. National Insitute of Health: National Institute on Drug Abuse, Apr 2005- Mar 2010. #R01 DA06733-10.

Publications, Most Recent

Skelton, M. R., Williams, M. T., McInturf, S.A., Rossi III, J., Aronow, B. J., Vorhees, C. V. (in preparation). Neonatal exposure to ±3,4-methelynedioxymethamphetamine alters NMDA receptor subunit 1, nNOS and PSD95 expression and LTP in adult rats.

Williams, M. T., Skelton, M. R., Longacre, I.D., Thompson, K.N., Maple, A.M., Vorhees, C. V., Brown, R.W. (in preparation). Neuronal reorganization of the nucleus accumbens, dentate gyrus, and entorhinal cortex in adult rats that received (±)-3,4-methylenedioxymethamphetamine as neonates.

Braun, A. A., Skelton, M. R., Vorhees, C.V., Williams, M. T. (in preparation). A comparison of the elevated plus maze and elevated zero maze under baseline conditions and following anxiolytic or anxiogenic treatments in Sprague-Dawley rats.

Vorhees, C. V., Morford, L.R., Skelton, M. R., Graham, D. L., Williams, M. T. (awaiting Eli Lilly approval). Periadolescent effects of fluoxetine and paroxetine compared on tests of anxiety, acoustic startle and forced swim in rats.

Grace, C. E., Schaefer, T.L., Graham, D. L., Skelton, M. R., Williams, M.T., Vorhees, C.V. (submitted 11-11-2009, IJDN). Effects of inhibiting neonatal methamphetamine-induced corticosterone release in rats by adrenal autotransplantation on later learning, memory, and plasma corticosterone levels.

Grace, C. E., Schaefer, T.L., Gudelsky, G. A., Williams, M.T., Vorhees, C.V. (submitted 10-27-2009, JNC). Neonatal adrenal autotransplantation in rats attenuates methamphetamine-induced increases in corticosterone without differentially altering brain monoamine reductions.

Schaefer, T.L., Grace, C. E., Gudelsky, G. A., Vorhees, C.V., Williams, M.T. (submitted 10-16-2009, Stress). Suppression of methamphetamine-induced corticosterone increases in neonatal rats with metyrapone, ketoconazole, or adrenalectomy: paradoxical and/or interactive effects are alleviated by adrenalectomy with autotransplantation.

Hemmerle, A.M., Dickerson, J.W., Herring, N.R., Schaefer, T.L., Vorhees, C.V., Williams, M.T., Seroogy K.B., (in revision JCN). (±)-3,4-Methylenedioxymethamphetamine (Ecstasy) treatment modulates expression of neurotrophins and their receptors in multiple regions of adult rat brain.

Herring, N. R., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (accepted with revision, Synapse). Dissociation of dopaminergic neurotoxicity and path integration learning deficits from hyperthermia after (+)-methamphetamine treatment in adrenalectomized rats.

Grace, C. E., Schaefer, T.L., Herring, N. R., Graham, D. L., Skelton, M. R., Gudelsky, G. A., Williams, M. T., Vorhees, C. V. (accepted with revision, NTT). The effects of a neurotoxic dose of (+)-methamphetamine on spatial and path integration learning, object recognition memory, motor performance, corticosterone, and monoamines in the adult C57BL/6 mouse.

Zhu, H., Mingler, M., McBride, M.L., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Williams, M.T., Vorhees, C.V., Rothenberg, M.E. (accepted with revision). NPSR1 is involved in stress reactivity and required for NPS induced hyperlocomotion and anti-anxiety activity. Psychoneuroendocrinology.

Sun, Y, Ran, H., Zamzow, M., Kitatani, K., Skelton, M.R., Williams, M.T., Vorhees, C.V., Witte, D.P., Hannun Y.A., Grabowski, G.A. (accepted with minor revision 8-13-2009, resubmitted 10-13-2009). Specific saposin C deficiency: CNS impairment and acid -glucosidase effects in the mouse. Human Molecular Genetics.

Sun, Y, Liou, B., Ran, H., Skelton, M.R., Williams, M.T., Vorhees, C.V., Kitatani, K., Hannun Y.A., Witte, D.P., Xu, Y.-H., Grabowski, G.A. (accepted with minor revision 8-13-2009 resubmitted 10-13-2009). Neuronopathic Gaucher disease in the mouse: Viable combined selective saposin C deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits. Human Molecular Genetics.

Graham, D. L., Herring, N. R., Schaefer, T.L., Vorhees, C.V., Williams, M.T. (in press). Glucose and corticosterone changes in developing and adult rats following exposure to (±)-3,4-methylendioxymethamphetamine or 5-methoxydiisopropyltryptamine. Neurotoxicology and Teratology.

Schaefer, T.L., Vorhees, C.V., Williams, M.T. (2009). Pet-1 deficient mice exhibit anxiety with hypoactivity and defensiveness but no cognitive deficits. Neuroscience, 164:1431-1443.

Vorhees, C. V., Skelton, M. R., Grace, C. E., Schaefer, T.L., Graham, D. L., Braun, A. A., Williams, M. T. (2009). Effects of (+)-methamphetamine on path integration and spatial learning, but not locomotor activity or acoustic startle, align with the stress hyporesponsive period in rats. International Journal of Developmental Neuroscience 27(3): 289-298.

Skelton, M. R., Schaefer, T.L., Herring, N. R., Vorhees, C.V., Williams, M.T. (2009). Comparison of the developmental effects of 5-methoxy-n,n-diisopropyltryptamine (foxy) to (±)-3,4-methylenedioxymethampetamine in rats. Psychopharmacology 204(2):287-297.

Vorhees, C. V., Schaefer, T. L., Skelton, M. R., Grace, C. E., Herring, N. R., Williams, M. T. (2009). ±3,4-Methylenedioxymethamphetamine (MDMA) dose-dependently impairs spatial learning in the Morris water maze after exposure of rats to different five-day intervals from birth to postnatal day 20.Developmental Neuroscience 31(1-2):107-120.

Vorhees, C. V., Johnson, H. L., Burns, L. N., Williams, M. T. (2009). Developmental treatment with the dopamine D2/3 agonist quinpirole selectively impairs spatial learning in the Morris water maze Neurotoxicology and Teratology. 31(1):1-10.

Loepke, A.W., Istaphanous, G.K., Miles, L., Hughes, E.A., McCann, J.C., Kurth, C.D., Williams, M.T., Vorhees, C.V., Danzer, S.C. (2009). Effects of neonatal isoflurane exposure in mice on brain cell viability, adult behavior, learning, and memory. Anesthesia & Analgesia. 108(1): 90-104.

Skelton, M. R., Able, J. A., Grace, C. E., Herring, N.R., Schaefer, T. L., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2008). (±)-3,4-methylenedioxymethamphetamine treatment in adult rats impairs path integration learning: A comparison of single vs once per week treatment for 5 weeks. Neuropharmacology. 55(7): 1121-1130.

Sun, Y., Jia, L., Williams M. T., Zamzow, M., Ran, H., Quinn, B., Aronow, B.J., Vorhees, C. V., Witte, D. P., Grabowski, G. A. (2008). Gene expression profiling and neurobehavioral assessments in prosaposin deficient mice: Molecular alterations precede neuronal deficits. BMC Neuroscience 9:76.

Herring, N.R., Schaefer, T. L., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2008). Effect of (+)-methamphetamine on path integration learning, novel object recognition, and neurotoxicity in rats. Psychopharmacology 199(4):637-650.

Vorhees, C. V., Herring, N.R., Schaefer, T. L., Grace, C. E., Skelton, M. R., Johnson, H. L., Williams, M. T. (2008). Effects of (+)-methamphetamine on path integration and spatial learning in rats: Effects of dose and rearing conditions. International Journal of Developmental Neuroscience 26(6):599-610.

Sun, Y., Witte, D.P., Ran, H., Zamzow, M., Barnes, S., Cheng, H., Han, X., Williams, M.T., Skelton, M.R., Vorhees, C.V., Grabowski, G.A. (2008). Neurological deficits and glycosphingolipid accumulation in Saposin B deficient mice. Human Molecular Genetics. 17:2345-2356.

Herring, N.R., Schaefer, T.L., Tang, P.H., Skelton, M.R., Lucot, J.P., Gudelsky, G.A., Vorhees, C.V., Williams, M.T. (2008). Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats.BMC Neuroscience 9:49.

Skelton, M. R., Williams, M. T., Vorhees, C. V. (2008). Developmental effects of 3,4-methylenedioxymethamphetamine: A review. Behavioural Pharmacology 19(2):91-111.

Schaefer, T. L., Skelton, M. R., Herring, N.R., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2008). Short- and long-term effects of (+)-methamphetamine and (±)-3,4-methylenedioxymethamphetamine on monoamine and corticosterone levels in the neonatal rat following multiple days of treatment. Journal of Neurochemistry 104:1674-1685.

Pan, D., Sciascia, A., Vorhees, C. V., Williams, M. T. (2008). Progression of multiple behavioral deficits during development in a murine model of Hurler Syndrome: Age of onset during development. Brain Research, 1188:241-253.

Grace, C. E., Schaefer, T. L., Herring, N.R., Skelton, M. R., McCrea, A. E., Vorhees, C. V., Williams, M. T. (2008). (+)-Methamphetamine increases corticosterone in plasma and BDNF in brain more than forced swim or isolation in neonatal rats. Synapse, 62(2):110-121.

Lingrel, J. B., Williams, M. T., Vorhees, C. V., Moseley A. E. (2007). Na,K-ATPase and the role of α isoforms. J Bioenergetics and Biomembranes. 39(5-6):385-9. (Review)

Vorhees, C. V., Skelton, M. R., Williams, M. T. (2007). Age-dependent effects of neonatal methamphetamine exposure on spatial learning. Behavioural Pharmacology, 18(5-6):549-562.

Skelton, M. R., Williams, M. T., Schaefer, T. L., Vorhees, C. V. (2007). Neonatal (+)-methamphetamine increases brain derived neurotrophic factor, but not nerve growth factor, during treatment and results in long-term spatial learning deficits. Psychoneuroendocrinology, 32(6): 734-745.

Williams, M. T.*, Herring, N.R.*, Schaefer, T. L., Skelton, M. R., Campbell N. G., Lipton, J. W., McCrea, A. E., Vorhees, C. V. (2007). Alterations in body temperature, corticosterone, and behavior following the administration of 5-methoxy-diisopropyltryptamine (‘Foxy’) to adult rats: A new drug of abuse. *denotes equal authorship. Neuropsychopharmacology 32: 1404-1420.

Vorhees, C. V., Schaefer, T. L., Williams, M. T. (2007). Developmental effects of ±3,4-methylenedioxymethamphetamine on spatial versus path integration learning: effects of dose distribution. Synapse 61(7): 488-499.

Moseley A. E.*, Williams, M. T.*, Schaefer, T. L., Bohanan, C. S., Behbehani, M. M., Vorhees, C. V., Lingrel, J. B. (2007). Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor activity and anxiety in mice. *denotes equal authorship. Journal of Neuroscience 27(3):616-626.

Skelton, M. R., Williams, M. T., Vorhees, C. V. (2006). Treatment with MDMA from P11-20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats. Psychopharmacology 189(3):307-318.

Thacker, S. K., Perna, M. K., Ward, J. J., Schaefer, T. L., Williams, M. T., Kostrzewa, R. M., Brown, R. W. (2006). The effects of adulthood olanzapine treatment on cognitive performance and neurotrophic factor content in male and female rats neonatally treated with quinpirole. European Journal of Neuroscience. 24:2075-2083.

Williams, M. T., Furay, A. F., Ehrman, L. A., Schaefer, T. L., Vorhees, C. V. (2006). Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure. Stress 9(3): 153-163.

Vorhees, C. V., Williams, M. T. (2006). Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1(2): 848-858.

Schaefer, T. L., Ehrman, L. A., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2006). A comparison of monoamine and corticosterone levels 24 hours following (+)methamphetamine, (±)3,4-methylenedioxymethamphetamine, cocaine, (+)fenfluramine, or (±)methylphenidate administration in the neonatal rat. Journal of Neurochemistry 98(5): 1369-1378.

Ehrman, L. A., Williams, M. T., Schaefer, T. L., Gudelsky, G. A., Reed, T. M., Fienberg, A. A., Greengard, P., Vorhees, C. V. (2006). Phosphodiesterase 1B modulates the effects of methamphetamine on locomotor activity and spatial learning through a DARPP32-dependent pathway: evidence from PDE1B-DARPP32 double knockout mice. Genes, Brain, and Behavior, 5: 540-551.

Able, J. A., Gudelsky, G. A., Vorhees, C. V., Williams, M. T. (2006). ±3, 4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory. Biological Psychiatry, 59(12): 1219-1226.

Crawford, C. A., Williams, M. T., Kohutek, J. L., Choi, F. A., Yoshida, S. T., McDougall, S. A., Vorhees, C. V. (2006). Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats. Brain Research, 1077: 178-186.

Brown, R. W., Perna, M. K., Schaefer, T. L., Williams, M. T. (2006). The effects of nicotine on D2-mediated behaviors and neurotrophins of rats neonatally treated with quinpirole. Synapse 59(5): 253-259

Presentations, Most Recent

Braun, A. A., Schaefer, T. L., Vorhees, C.V., Williams, M. T. Functional alterations in the 5HT1A receptor following neonatal +/-3,4-methylenedioxymethamphetamine (MDMA) exposure in rats. Poster. Annual Meeting, International Behavioral Neuroscience Society. Nassau, Bahamas. 2009.

Skelton M.R., Vorhees, C.V., Graham, D. L., Schaefer, T. L., Grace C. E, Braun, A. A., Williams, M. T. Examining critical periods of neonatal 3,4-(±)-methylenedioxymethamphetamine (MDMA) administration on behavior. Poster. Annual Meeting, International Behavioral Neuroscience Society. Nassau, Bahamas. 2009.

Sun, Y., Ran, H., Zamzow, M., Kitatani, K., Skelton, M.R., Williams, M.T., Vorhees, C.V., Witte, D.P., Hannun, Y.A., Xu, Y-H., Grabowski, G.A. Role of saposin C in CNS impairment and in vivo function of acid β-glucosidase (GCase). Annual Meeting, American Society of Human Genetics. Honolulu, HI. November, 2009.

Williams, M. T. A model of (+)-methamphetamine use in adults. Francis Crick Lecture Series, University of Evansville, Evansville, IN, April, 2009.

Sun, Y., Kitatani, K., Witte, D.P., Ran, H., Liou, B., Zamzow, M., Skelton, M.R., Williams, M.T., Vorhees, C.V., Hannun, Y.A., Grabowski, G.A. Pathological studies and therapeutic testing of isofagomine in a viable mouse model of neuronopathic Gaucher disease. Annual Meeting, American Society of Human Genetics. Philadelphia, PA. November, 2008.

Sun, Y., Kitatani, K., Witte, D.P., Ran, H., Liou, B., Skelton, M.R., Williams, M.T., Vorhees, C.V., Hannun, Y.A., Grabowski, G.A. A viable mouse model of neuronopathic Gaucher disease: Acid β-glucosidase V394L/saposin C deficient mice have CNS glucosylsphingosine and glucosylceramide accumulation and progressive neurological deficits. Poster. Lysosomal Diseases and the Brain Conference. Sacremento, CA. May, 2008.

Braun, A.A., Skelton, M.R., Vorhees, C.V.; Williams, M.T. A comparison of the elevated plus and elevated zero maze with or without diazepam in rats. Poster. Annual Meeting, International Behavioral Neuroscience Society. St. Thomas, Virgin Islands. June, 2008.

Schaefer, T.L.; Vorhees, C.V.; Williams, M.T. Cognition, anxiety, and depressive-like behaviors in Pet-1 knock-out mice. Poster. Annual Meeting, International Behavioral Neuroscience Society. St. Thomas, Virgin Islands. June, 2008.

Graham, D.L., Grace, C.E., Schaefer, T.L.; Skelton, M.R., Vorhees, C.V.; Williams, M.T. Housing conditions but not Pb2+ during the neonatal period in rats interacts with an acute stressor on corticosterone release. Poster. Annual Meeting, International Behavioral Neuroscience Society. St. Thomas, Virgin Islands. June, 2008.

Skelton, M.R., Grace, C.E., Schaefer, T.L.; Vorhees, C.V.; Williams, M.T. The role of angiotensinogen in behavioral deficits induced by neonatal mdma exposure. Poster. Annual Meeting, International Behavioral Neuroscience Society. St. Thomas, Virgin Islands. June, 2008.

Grace, C.E., Williams, M.T., Vorhees, C.V. Adult HPA axis responsivity to forced swim or isolation following neonatal exposure of rats to (+)-methamphetamine. Poster. Annual Meeting, International Behavioral Neuroscience Society. St. Thomas, Virgin Islands. June, 2008.

Williams, M. T., Herring, N. R., Schaefer, T. L., Vorhees, C. V. Effects of (+)-methamphetamine on learning and memory and neurotoxicity in the adult rats. University of Sydney, Sydney, AU (July 2007). Mini-Symposium “Party Drugs: Effects on Brain and Behaviour,” Sydney, Austrialia, July 20, 2007.

Vorhees, C.V. (Invited speaker), Herring, N.R., Schaefer, T.L., Skelton, M.R., Grace, C.E., Miranowski, S.K., and Williams, M.T. Developmental methamphetamine: Effects of dose and rearing condition on later path integration and spatial learning. University of Sydney, Mini-Symposium “Pary Drugs: Effects on Brain and Behaviour,” Sydney, Austrialia, July 20, 2007.

Schaefer, T.L. (Invited speaker), Skelton, M.R., Herring, N.R., Vorhees, C.V., and Williams, M.T. The effects of developmental psychostimulant exposure on serotonine and corticosterone. University of Sydney, Mini-symposium “Pary Drugs: Effects on Brain and Behaviour,” Sydney, Austrialia, July 20, 2007.

Vorhees, C.V. (Invited speaker), Schaefer, T.L., Skelton, M.R., and Williams, M.T. Developmental effects of MDMA on learning and memory. Seminar at the Victoria University of Wellington, Wellington, New Zealand, July 24, 2007.

Jia, L., Sun, Y., Williams, M.T., Zamzow, M., Ran, H., Quinn, B., Aronow, B.J., Vorhees, C.V., Witte, D.P., and Gregory A. Grabowski. CEBP is a candidate regulator of brain disease in prosaposin deficiency mice. Annual Meeting, American Society of Human Genetics. San Diego, CA. October, 2007.

Sun, Y., Ran, H., Zamzow, M., Quinn, B., Williams, M.T., Vorhees, C.V., Witte, D.P., Cheng, H., Han, X., Grabowski, G.A. Saposin B deficiency in mice leads to sulfatide and lactosylceramide accumulation and slowly developed neurological deficit. Annual Meeting, American Society of Human Genetics. San Diego, CA. October, 2007.

Curran, C.P., Dalton, T. P., Williams, M.T., Vorhees, C.V., Nebert, D.W. Maternal-fetal distribution of PCB 153 versus PCB 169 in cyp1a2(-/-) knockout compared with cyp1a2(+/+) wild-type mice. Annual Meeting, Society of Toxicology. March, 2007.