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Background

Dr. William Slikker, Jr. is the director of FDA’s National Center for Toxicological Research (NCTR). He received his Ph.D. in pharmacology and toxicology from the University of California at Davis. Dr. Slikker holds adjunct professorships in the Department of Pediatrics, as well as the Department of Pharmacology and Toxicology at the University of Arkansas for Medical Sciences. He has held committee chairmanships or elected offices in several scientific societies; including the Teratology Society (serving as president) and the American Society for Pharmacology and Experimental Therapeutics (chair, Developmental Pharmacology Section and member, Program Committee). Dr. Slikker is also the co-founder and past president of the MidSouth Computational Biology and Bioinformatics Society. He is currently associate editor for NeuroToxicology and associate editor for the “Environmental Health” section of Experimental Biology and Medicine. He is the past president of The Academy of Toxicological Sciences and the Society of Toxicology. He is a recipient of the 2014 George H. Scott Memorial Award from The Toxicology Forum and was invited to present the Warkany Lecture at the 2015 annual meeting of the Teratology Society. In early 2019, the Academy of Toxicological Sciences selected Dr. Slikker to receive the prestigious Mildred S. Christian Career Achievement Award.

Research Interests

Dr. Slikker has authored or co-authored over 350 publications in the areas of transplancental pharmacokinetics, developmental neurotoxicology, neuroprotection, systems biology, and risk assessment. Dr. Slikker’s recent research has highlighted the concern for thousands of infants and toddlers who undergo longer-duration general anesthesia. He has performed research with his team and published over 25 peer-reviewed papers outlining the issue of brain-cell death and cognitive-function deficits in animal models that may result from several hours of anesthesia at a critical time of development. He has also, with the use of in vitro and in vivo techniques in rodents and nonhuman primates, defined possible mechanisms of toxicity and protective pathways to prevent the detrimental effects of general anesthesia. Through these and related scientific contributions, he has identified and characterized a host of minimally-invasive biomarkers of neurotoxicity including the use of preclinical imaging (MRI, MicroPET/CT), genomic and lipidomics analysis, and modeling approaches to characterize and quantify adult and developmental neurotoxicity. As an indicator of the impact of Dr. Slikker’s research on his chosen field, he and co-editors have recently published the Second Edition of the “Handbook of Developmental Neurotoxicology” comprised of over 45 chapters and representing the breadth and depth of this exciting and important area of research. He has also served on several national/international advisory panels for the International Life Sciences Institute (ILSI)/Health and Environmental Sciences Institute (HESI), Chemical Industry Institute of Toxicology (CIIT) Centers for Health Research, Environmental Protection Agency (EPA), National Institute of Environmental Health Sciences (NIEHS), National Academy of Sciences (NAS), National Institutes of Health (NIH) and World Health Organization (WHO). 

Professional Societies and National and International Groups

Society of Toxicology
President
2012-2013

International Congress on Toxicology Organizing Committee for ICTXV
Chair
2013-2019

Select Publications

Publication titles are linked to text abstracts on PubMed.

Handbook of Developmental Neurotoxicology, 2nd Edition.
Slikker W. Jr., Paule M.G., Wang C., and Editors.
Academic Press. 2018.

Characterization of Biaxial Stretch as an In Vitro Model of Traumatic Brain Injury to the Blood-Brain Barrier.
Rosas-Hernandez H., Cuevas-Martinez E.Y., Lourdes C.E., Lantz S.L., Gomez-Crisostomo N.P., Sturdivant N., Balachandran K., Imam S.Z., Slikker W.Jr., Paule M.G., and Ali S.F.
Mol. Neurobiology. 2018, 55:1, 258-266.

Changes in the Metabolome and MicroRNA Levels in Biological Fluids Might Represent Biomarkers of Neurotoxicity: A Trimethyltin Study.
Imam S., He Z.,  Cuevas E., Rosas-Hernandez H., Lantz S.M., Sumit S., Raymick J., Robinson B., Hanig J.P., Herr D., MacMillan D., Smith A., Liachenko S., Ferguson S., O’Callaghan J., Miller D., Somps C., Pardo I.D., Slikker W. Jr., Pierson J.B., Roberts R., Gong B., Tong W., Aschner M., Kallman M.J., Calligaro D., and Paule M.G.
Experimental Biology and Medicine. 2018, 243:3, 228-236.

Biomarkers and their Impact on Precision Medicine.
Slikker W. Jr.
Thematic Issue on Biomarkers and their Impact on Precision Medicine. 2018, 243:3, 211-212.

Lipid Profiling as an Effective Approach for Identifying Biomarkers/Adverse Events Associated with Pediatric Anesthesia.
Wang C., Han X., Liu F., Patterson T.A., Hanig J.P., Paule M.G., and Slikker W. Jr.
Toxicology and Applied Pharmacology. 2018, 354,191-195.

Evaluation of Dopamine Receptor Integrity after Sevoflurane Exposure in Neonatal Rat Brain Using Positron Emission Tomography.
Yin Q., Paule M.G., Patterson T.A., Liu F., Fogle C.M., Apana S.M., Berridge M.S., Slikker W. Jr., Wang C., and Zhang X.
Global Journal of Anesthesiology. 2018, Vol 5(1),1-6.

Electron Microscopy Techniques Employed to Explore Mitochondrial Defects in the Developing Rat Brain Following Ketamine Treatment.
Eustaquio T.V., Wang C., Dugard C.K., George N.I., Liu F., Slikker W. Jr., Paule M.G., Howard P.C., and Paredes A.M.
Experimental Cell Research. 2018, 373(1-2):164-170.

Emerging Technologies for Food and Drug Safety.
Slikker W. Jr., Tong W., Thakkar S., Patri A.K., Valdez M., Shi L., De Souza Lima T., Archella D., Barton-Maclaren T., Bo L., Buvinich D., Chaudhry Q., Chuan P., Deluyker H., Domselaar G., Freitas M., Hardy B., Eichler H., Hugas M., Lee K., Liao C., Loo L., Okuda H., Orisakwe O. E., Sactitono C., Silva P., Whelan M., and Zhao-Wong A.
Regulatory Toxicology and Pharmacology. 2018, 98:115-128.

Lipidomics Reveals Changes of Metabolism, Indicative of Anesthetic-Induced Neurotoxicity in Developing Brains.
Wang C., Wang C., Liu F., Rainosek S.W., Patterson T.A., Slikker W. Jr., and Han X.
Chemical Research in Toxicology. 2018, 31(9):825-835.

Regulatory Bioinformatics for Food and Drug Safety.
Healy M.J., Tong W., Ostroff S., Eichler H.G., Patak A., Neuspiel M., Deluyker H., and Slikker W. Jr.
Regulatory Toxicology and Pharmacology. 2016, 80:342-7; doi 10.1016/j.yrtph.2016.05.021.

In Vivo Monitoring of Sevoflurane-Induced Adverse Effects in Neonatal Nonhuman Primates Using Small-animal Positron Emission Tomography.
Zhang X., Liu S., Newport G.D., Paule M.G., Callicott R., Thompson J., Liu F., Patterson T.A., Berridge M.S., Apana S.M., Brown C., Maisha M., Hanig J.P., Slikker W. Jr., and Wang C.
Anesthesiology. 2016, 125(1):133-46; doi: 10.1097/ALN.0000000000001154.

Relationship Between Ketamine-Induced Developmental Neurotoxicity and NMDA Receptor-Mediated Calcium Influx in Neural Stem Cell-Derived Neurons.
Wang C., Liu F., Patterson T.A., Paule M.G., and Slikker W. Jr.
Neurotoxicology. 2016; pii: S0161-813X(16)30060-2; doi: 10.1016/j.neuro.2016.04.015.

Translational Biomarkers of Neurotoxicity: A Health and Environmental Sciences Institute Perspective on the Way Forward.
Roberts R.A., Aschner M., Calligaro D., Guilarte T.R., Hanig J.P., Herr D.W., Hudzik T.J., Jromin A., Kallman M.J., Liachenko S., Lynch J.J. 3rd, Miller D.B., Moser V.C., O’Callaghan J.P., Slikker W. Jr., and Paule M.G.
Toxicological Sciences. 2015; 18(2):332-40; doi: 10.1093/toxsci/kfv188.

Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.
Liu F., Rainosek S.W., Frisch-Daiello J.L., Patterson T.P., Paule M.G., Slikker W. Jr., Wang C., and Han X.
Toxicological Sciences. 2015, 147(2), 562-572; doi: 10.1093/toxsci/kfv150 [Epub 2015 ahead of print July 23, 2015].

Genomics in the Land of Regulatory Science.
Tong W., Ostroff S., Blais B., Silva P., Dubuc M., Healy M., and Slikker W.
Regulatory Toxicology and Pharmacology. 2015, 72(1), 102-106; dx.doi.org/10.1016/j.yrtph.2015.03.008.

Opportunities To Integrate New Approaches in Genetic Toxicology: A ILSI-HESI Workshop Report.
Zeiger E., Gollapudi B., Aardema M.J., Auerbach S., Boverhof D., Custer L., Dedon P., Honma M., Ishida S., Kasinski A.L., Kim J., Manjanatha M.G., Marlowe J., Pfuhler S., Pogribny I., Slikker W., Stankowski L.F., Tanir J.Y., Tice R., van Bethem J., White P., Witt K.L., and Thybaud V.
Environmental and Molecular Mutagenesis. 2014, DOI 10.1002/em.

Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates.
Yang X., Morris S.M., Gearhart J.M., Ruark C.D., Paule M.G., Slikker W. Jr., Mattison D.R., Vitiello B., Twaddle N.C., Doerge D., Young J.F., and Fisher J.W.
PLoS One. 2014, 9(9):e106101. Doi:10.1371/journal.pone0106101 September 2014.

Of Human-On-A-Chip and Humans: Considerations for Creating and Using Microphysiological Systems.
Slikker W. Jr.
Experimental Biology and Medicine. (Mayood, N.J.); DOI: 10.1177/1535370214537754 [Epub July 2014].

Protective Effect of Acetyl-l-Carnitine on Propofol-Induced Toxicity in Embryonic Neural Stem Cells.
Liu F., Rainosek S.W., Sadovova N., Fogle C.M., Patterson T.A., Hanig J.P., Paule M.G., Slikker W. Jr., and Wang C.
Neurotoxicology. 2014, 42: 49-57. pii: D0161-813X(14)00055-2. Doi: 10.1016/j.neuro.2014.03.011. [Epub ahead of print].

Porcine Brain Microvessel Endothelial Cells Show Pro-Inflammatory Response to the Size and Composition of Metallic Nanoparticles.
Trickler W.J., Lantz-McPeak S.M., Robinson B.L., Paule M.G., Slikker W. Jr., Biris A.S., Schlager J.J., Hussain S.M., Kanungo J., Gonzalez C., and Ali S.F.
Drug Metab Rev. 2014, 46(2):224-231; doi: 10.3109/03602532.2013.873450 [Epub Dec 31, 2013].

Application of microPET Imaging Approaches in the Study of Pediatric Anesthetic-Induced Neuronal Toxicity.
Zhang X., Paule M.G., Wang C., and Slikker W. Jr.
J Appl Toxicol. 2013, 33(9):861-868; doi:10.1002/jat.2857 [Epub Feb 11, 2013].

Utilization of Neural Stem Cell-Derived Models to Study Anesthesia-Related Toxicity and Protection.
Wang C., Liu F., Patterson T.A., Paule M.G., and Slikker W. Jr.
Molecular Neurobiology. 2013, 48(2):302-307 [Epub July 12, 2013].

Anaesthetic Neurotoxicity and Neuroplasticity: An Expert Group Report and Statement Based on the BJA Salzburg Seminar.
Jevtovic-Todorovic V., Absalom A.R., Blomgren K., Brambrink A., Crosby G., Culley D.J., Fiskum G., Giffard R.G., Herold K.F., Loepke A.W., Ma D., Orser B.A., Planel E., Slikker W. Jr., Soriano S.G., Stratmann G., Vutskits L., Xie Z., and Hemmings H.C. Jr.
Br J Anaesth. 2013, 111(2):143-151; doi:10.1093/bja/aet177 [Epub May 30, 2013].

Neuroprotective Efficacy of a New Brain-Penetrating C-Abl Inhibitor in a Murine Parkinson’s Disease Model.
Imam S.Z., Trickler W., Kimura S., Binienda Z.K., Paule M.G., Slikker W. Jr., Li S., Clark R.A., and Ali S.F.
PLoS One. 2013, 8(5):e65129; doi:10.1371/journal.pone.0065129.

Ketamine-Induced Neuronal Damage and Altered N-Methyl-D-Aspartate (NMDA) Receptor Function in Rat Primary Forebrain Culture.
Liu F., Patterson T.A., Sadovova N., Zhang X., Liu S., Zou X., Hanig J.P., Paule M.G., Slikker W. Jr., and Wang C.
Toxicol Sci. 2013, 131(2):548-557 [Epub Oct 11, 2012].

2012 Global Summit on Regulatory Science (GSRS-2012) – Modernizing Toxicology.
Miller M.A., Tong W., Fan X., and Slikker W.
Toxicological Sciences. 2013, 131(1):9-12; doi:10.1093/toxsci/kfs254 [Epub Aug 24, 2012].

What It Means to be Global.
Roberts R.A., Wallis R., Ren J., van der Laan J.W., Sausen P.J., and Slikker W. Jr.
Toxicol Sci. 2012, 127(1):313-314 [Epub Feb 14 2012].

Advancing Global Health Through Regulatory Science Research: Summary of the Global Summit on Regulatory Science Research and Innovation.
Slikker W. Jr., Miller M.A., Valdez M.L., and Hamburg M.A.
Regulatory Toxicol Pharmacol. 2012, 62(3):471-473 [Epub Feb 7, 2012].

Pubertal Delay in Male Nonhuman Primates (Macaca Mulatta) Treated with Methylphenidate.
Mattison D., Plant T., Lin H., Chen H., Chen J.J., Twaddle N.C., Doerge D.R., Slikker W., Patton R.E., Hotchkiss C.E., Callicott J., Schrader S.M., Turner T.W., Kesner J.S., Vitiello B., Petibone D., and Morris S.M.
Proceedings of the National Academy of Sciences. 2011, 108(39):16301-16306.