Staff Fellow — Division of Biochemical Toxicology
Xiaoxia Yang, Ph.D.
Dr. Xiaoxia Yang received a bachelor’s degree in pharmacy from West China University of Medical Sciences in 1999 and a master’s degree in pharmaceutical analysis from the National Institutes for Food and Drug Control in China in 2002. In 2007, Dr. Yang obtained a Ph.D. in pharmacology from the National University of Singapore, where she conducted pharmacodynamic and pharmacokinetic investigations on the protective effects of thalidomide and St. John’s Wort against the toxicities induced by Irinotecan, a chemotherapeutic agent. After her Ph.D. studies, she accepted a postdoctoral fellowship in the Department of Pharmacology, Toxicology and Therapeutics at Kansas University Medical Center, where she evaluated the role of the nuclear receptor RXR-α in the regulation of multiple molecular signaling pathways controlling liver regeneration. From 2009-2011, Dr. Yang continued her postdoctoral training in the College of Pharmacy at Ohio State University, where she independently characterized the potential pharmacokinetic interactions between lenalidomide and temsirolimus, and demonstrated potential P-glycoprotein-mediated drug-drug interactions.
In 2011, Dr. Yang joined NCTR as an FDA commissioner’s fellow and was converted to an FDA staff fellow in 2013. Since joining NCTR, she has led several broad and complex computational modeling projects for the integration of toxicological information for consumer products, drugs, and tobacco-product constituents across different species and life stages as a function of internal doses. Dr. Yang independently developed physiologically based pharmacokinetic models to characterize Bisphenol A (BPA) internal dosimetry at different developmental stages across different species, and applied these models for the extrapolation of animal data to humans. This project provided critical information for FDA to make science-based regulatory decisions with respect to the use of BPA. Her advice has been requested and her BPA PBPK models have been incorporated by scientists within the FDA, other government agencies, academia, industry, and by international researchers.
Dr. Yang also developed a novel computational method to better understand the kinetic behaviors of the drug to treat Attention-Deficit/Hyperactivity Disorder, methylphenidate (MPH), across different species and age groups, and derived human-equivalent doses in children relevant to the reported pubertal delays in juvenile nonhuman primates ─ emphasizing the importance of pharmacovigilance for the safe use of MPH. With the integration of a sophisticated approach to characterize the kinetic behavior of extended release MPH formulations in the gastrointestinal tract, Dr. Yang extended the earlier-developed PBPK model to describe the diversity of absorption profiles observed among different extended-release MPH formulations. Guided by computational modeling, along with the extrapolation of toxicological information across species and in vitro versus in vivo systems, she has also helped experimental design and dose selection for ongoing studies at NCTR.
Throughout her education and early career, Dr. Yang established herself as an independent scientist with excellent abilities in the field of pharmacology and computational modeling. She has published 30 manuscripts, one book chapter, and 17 abstracts that have been presented at national and international scientific meetings. As an acknowledgement of her impact in her research fields, Dr. Yang’s contributions have been recognized by the American Society for Investigative Pathology as “outstanding research in experimental pathology” and by the Risk Assessment Specialty Section of the Society of Toxicology as having written “one of the best papers demonstrating application of risk assessment,” Dr. Yang has mentored and trained postdoctoral fellows and other staff members.
Dr. Yang’s research has been focused on both pre-clinical and clinical pharmacokinetics, with the aim to understand the mechanisms involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs and chemicals. This includes in vitro ADME studies using various in vitro cellular and subcellular models as well as working toward the development of LC-MS/MS methods for the quantification of drug/chemical concentrations in plasma and tissues. She has also worked on liver regeneration and the underlying molecular mechanisms, in vivo preclinical and clinical pharmacokinetic studies, and drug-drug interactions.
Dr. Yang’s current research interests focus on the development and utilization of computational models (e.g. PBPK/PD) to assess the internal dose metrics of environmental chemicals, drugs, and tobacco-product constituents ─ across different species, routes of exposure, and life stages.
- Quantitative characterization of the internal dose metrics of chemicals and drugs, in particular for vulnerable populations, e.g. pregnant women and children.
- Evaluation of drug absorption, with the utilization of sophisticated mechanistic approaches to account for the physiology of the gastrointestinal tract, physicochemical properties of drugs, and formulation-related information.
- In vitro-to-in vivo extrapolation of toxicological information for drug safety evaluation and human health risk assessment
- Integration of toxicological information across species as a factor of internal dose metrics.
- Incorporation of Monte Carlo analysis for inter-individual variability assessment.
- Assisting in experimental designs and dose selection using advanced and complex computational tools.
Dr. Yang’s research goals are to develop and utilize computational tools to provide scientific guidance and assist in the regulation of drugs, consumer products, and tobacco products by the agency.
Professional Societies/National and International Groups
Society of Toxicology
2012 – Present
Development of a Physiologically Based Pharmacokinetic Model for Assessment of Human Exposure to Bisphenol A.
Yang X, Doerge DR, Teeguarden JG, Fisher JW.
Toxicol Appl Pharmacol. 2015 Dec 15; 289 (3):442-56.
24-Hour Human Urine and Serum Profiles of Bisphenol A: Evidence Against Sublingual Absorption Following Ingestion in Soup.
Teeguarden JG, Twaddle N, Churchwell MI, Yang X, Fisher JW, Seryak LM, and Doerge DR.
Toxicol Appl Pharmacol. 2015 Oct 15; 288(2):131-42.
Unraveling Bisphenol A Pharmacokinetics Using Physiologically Based Pharmacokinetic Modeling.
Yang X, Fisher JW.
Front Pharmacol. 2015 Jan 9; 5:292.
Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates.
Yang X, Morris SM, Gearhart JM, Ruark CD, Paule MG, Slikker W Jr, Mattison DR, Vitiello B, Twaddle NC, Doerge DR, Young JF, Fisher JW.
PLoS One. 2014 Sep 3; 9(9):e106101.
The Hypothalamic-Pituitary-Thyroid Axis in Infants and Children: Protection from Radioiodines.
Fisher JW, Yang X, Harris C, Koturbash I, Lumen A.
J Thyroid Res. 2014 May 25; 710178.
Sensitive Liquid Chromatography/Mass Spectrometry Methods for Quantification of Pomalidomide in Mouse Plasma and Brain Tissue.
Jiang Y, Wang J, Rozewski DM, Kolli S, Wu CH, Chen CS, Yang X, Hofmeister CC, Byrd JC, Johnson AJ, Phelps MA.
J Pharm Biomed Anal. 2014 Jan; 88:262-8.
Prediction and Evaluation of Route Dependent Dosimetry of BPA in Rats at Different Life Stages Using a Physiologically Based Pharmacokinetic Model.
Yang X, Doerge DR, Fisher JW.
Toxicol Appl Pharmacol. 2013 Jul 1; 270(1):45-59.
Pharmacokinetics and Tissue Disposition of Lenalidomide in Mice.
Rozewski DM1, Herman SE, Towns WH 2nd, Mahoney E, Stefanovski MR, Shin JD, Yang X, Gao Y, Li X, Jarjoura D, Byrd JC, Johnson AJ, Phelps MA.
AAPS J. 2012 Dec; 14(4):872-82.
Absorption and Disposition of Bromate in F344 Rats.
Bull RJ, Kolisetty N, Zhang X, Muralidhara S, Quiñones O, Lim KY, Guo Z, Cotruvo JA, Fisher JW, Yang X, Delker D, Snyder SA, Cummings BS.
Toxicology. 2012 Oct 9; 300(1-2):83-91.
6β-Naltrexol, a Peripherally Selective Opioid Antagonist That Inhibits Morphine-Induced Slowing of Gastrointestinal Transit: An Exploratory Study.
Yancey-Wrona J, Dallaire B, Bilsky E, Bath B, Burkart J, Webster L, Magiera D, Yang X, Phelps M, Sadee W.
Pain Med. 2011 Dec; 12(12):1727-37.
Phase I Trial of Lenalidomide and CCI-779 in Patients with Relapsed Multiple Myeloma: Evidence for Lenalidomide-CCI-779 Interaction Via P-Glycoprotein.
Hofmeister CC, Yang X, Pichiorri F, Chen P, Rozewski DM, Johnson AJ, Lee S, Liu Z, Garr CL, Hade EM, Ji J, Schaaf LJ, Benson DM Jr, Kraut EH, Hicks WJ, Chan KK, Chen CS, Farag SS, Grever MR, Byrd JC, Phelps MA.
J Clin Oncol. 2011 Sep 1; 29(25):3427-34.
Dose Escalation of Lenalidomide in Relapsed or Refractory Acute Leukemias.
Blum W, Klisovic RB, Becker H, Yang X, Rozewski DM, Phelps MA, Garzon R, Walker A, Chandler JC, Whitman SP, Curfman J, Liu S, Schaaf L, Mickle J, Kefauver C, Devine SM, Grever MR, Marcucci G, Byrd JC.
J Clin Oncol. 2010 Nov 20; 28(33):4919-25.
Deregulation of Growth Factor, Circadian Clock, and Cell Cycle Signaling in Regenerating Hepatocyte RXRalpha-Deficient Mouse Livers.
Yang X, Guo M, Wan YJ.
Am J Pathol. 2010 Feb; 176(2):733-43.
Gender Disparity of Hepatic Lipid Homoeostasis Regulated by the Circadian Clock.
Yang X, Zhang YK, Esterly N, Klaassen CD, Wan YJ.
J Biochem. 2009 May; 145(5):609-23.
Simultaneous Determination of Irinotecan (CPT-11) and SN-38 in Tissue Culture Media and Cancer Cells by High Performance Liquid Chromatography: Application to Cellular Metabolism and Accumulation Studies.
Hu ZP, Yang XX, Chen X, Chan E, Duan W, Zhou SF.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 May 1; 850(1-2):575-80.
Pharmacokinetic Mechanisms for Reduced Toxicity of Irinotecan by Coadministered Thalidomide.
Yang XX, Hu ZP, Chan SY, Duan W, Ho PC, Boelsterli UA, Ng KY, Chan E, Bian JS, Chen YZ, Huang M, Zhou SF.
Curr Drug Metab. 2006 May; 7(4):431-55.
Herb-Drug Interactions: A Literature Review.
Hu Z, Yang X, Ho PC, Chan SY, Heng PW, Chan E, Duan W, Koh HL, Zhou S.
Drugs. 2005; 65(9):1239-82.
Determination of Thalidomide by High Performance Liquid Chromatography: Plasma Pharmacokinetic Studies in the Rat.
Yang X, Hu Z, Chan SY, Ho PC, Chan E, Duan W, Goh BC, Zhou S.
J Pharm Biomed Anal. 2005 Sep 1; 39(1-2):299-304.
Novel Agents that Potentially Inhibit Irinotecan-Induced Diarrhea.
Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S.
Curr Med Chem. 2005; 12(11):1343-58.
Simultaneous Determination of the Lactone and Carboxylate Forms of Irinotecan (CPT-11) and its Active Metabolite SN-38 by High-Performance Liquid Chromatography: Application to Plasma Pharmacokinetic Studies in the Rat.
Yang X, Hu Z, Chan SY, Goh BC, Duan W, Chan E, Zhou S.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jul 25; 821(2):221-8.
- Contact Information
- Xiaoxia Yang
- (870) 543-7391