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Xinxin Ding

Professor of Nanobioscience; Director of Laboratory of Molecular Toxicology; and Director of Center for Preclinical Nano-Drug Discovery and Development


Education:
  • Nanjing University, Nanjing, China, B.S. in Biology (Medical Physiology) (1982)
  • The University of Michigan Medical School, Ph.D. in Biological Chemistry (1988)
  • The University of Michigan Medical School, Postdoc (1988-89)

Past Professional Experience (selected):

  • Professor and Director of Toxicology Track (2004-2014), Department of Environmental Health Sciences, School of Public Health, University at Albany, SUNY
  • Professor of Molecular Genetics and Neuroscience (2004-2014), Department of Biomedical Sciences, School of Public Health, University at Albany, SUNY
  • Chief (2007-2014), Laboratory of Molecular Toxicology, Division of Environmental Health Sciences, Wadsworth Center, NYSDOH

Areas of Research:

  • Carcinogenesis
  • Disease Prevention
  • Drug Safety
  • Drug/Xenobiotic Metabolism
  • Molecular/Mechanistic Toxicology
  • Nanomedicine
  • Nanotoxicology
  • Pharmacogenomics

Research Description:

One of my research goals is to gain basic knowledge on enzyme function, regulation, and genetics, which can be applied to translational research for improvements in drug safety and efficacy for major human diseases, such as Alzheimer’s. Another goal is to develop a better understanding of the process of chemical (including cigarette smoke)-induced lung toxicity, including lung tumorigenesis, and to identify genetic and environmental factors that influence the risks of developing lung cancer, the leading cause of cancer-related death in the U.S. Current studies are focused on the function and regulation of microsomal cytochrome P450 enzymes in various organ systems, including the lung. The P450 enzymes metabolize numerous drugs, chemical carcinogens, environmental pollutants, as well as endogenous signaling molecules. A major area of research involves development and application of genetically engineered mouse models for functional studies. We have produced a series of novel mouse models with tissue-selective deletion or down-regulation of the P450 reductase gene, as well as mouse models that either have selected mouse P450 genes deleted, and/or produce human P450 enzymes. These animals are being used to model human genetic deficiency, and to explore the role of P450 enzymes in drug response, carcinogenesis, and disease susceptibility. Complementary to studies in animal models, we are also studying expression and genetic polymorphisms of human P450 and P450 reductase genes, in order to identify the genetic basis for inter-individual differences in clinical response to drug therapy, and to predict the lung cancer risks of exposure to commonly occurring environmental chemicals, such as naphthalene. Furthermore, we are initiating basic as well as preclinical studies on the pharmacology of nano-drugs that are designed to improve therapeutic efficacy and safety profile, or to provide better protection against environmental diseases.

Honors and Awards (selected):

  • Fogarty International Research Collaboration Award, Fogarty International Center, NIH, 1999-2002
  • Standing Member, Alcohol and Toxicology Study Section (1), CSR, NIH, 2000-2003 
  • Standing Member, Lung Injury, Repair, and Remodeling Study Section, CSR, NIH, 2004
  • Secretary/Treasurer, Drug Metabolism Division, American Society for Pharmacology and Experimental Therapeutics, 2005-2006
  • Distinguished Chinese Toxicologist Lectureship Award, the American Association of Chinese in Toxicology, Society of Toxicology, 2008
  • Chair, Program Committee for the 18th International Symposium on Microsomes and Drug Oxidations, Beijing, China, 2010
  • Standing member, NIH Xenobiotic and Nutrient Disposition and Action (XNDA) Study Section, 2013-2017
  • Member, Scientific Advisory Board, 20th International Microsomes and Drug Oxidations Meeting, Stuttgart, Germany, 2014
Invited Speaker at Symposia; Lectureship (selected):
  • 16th North American ISSX Meeting, Baltimore, 2009
  • Beijing International Meeting on Research in Taste and Smell, Beijing, 2009
  • 5th Applied Pharmaceutical Analysis conference (The Boston Society of Advanced Therapeutics), Boston, 2009
  • American Association of Pharmaceutical Scientists Webinar, 2009
  • Vanderbilt University, 2009
  • Indiana University School of Medicine, 2010
  • International Symposium on Pharmacogenomics and the Regulation of Drug Metabolism Enzymes and Genes, Nanjing, China, 2010
  • Peking Union Medical College and Chinese Academy for Medical Sciences, Beijing, 2010
  • University of Pittsburgh, 2010
  • 50th Society of Toxicology annual meeting, Washington DC, 2011
  • 17th North American ISSX Meeting, Atlanta, 2011
  • University of Maryland, Baltimore, 2011
  • Johns Hopkins University, Baltimore, 2012
  • Experimental Biology Meeting, San Diego, 2012
  • University of Kansas Medical Center, 2012
  • University of California, Los Angeles, 2013
  • Loma Linda University, 2013
  • Gordon Research Conference on Drug Metabolism, Plymouth, NH, 2013
  • 10th International ISSX Meeting (chair of plenary session), Toronto, Canada, 2013
  • The Chinese University of Hong Kong, 2013
  • University of Connecticut, Storrs, 2014
  • St. Jude Children’s Research Hospital, Memphis, 2014
Editorial Boards (selected):

Member:

  • Toxicology and Applied Pharmacology (2000-2015)
  • Journal of Biochemical and Molecular Toxicology (2007-)
  • Journal of Biological Chemistry (2009-2014)

Associate Editor:

  • Drug Metabolism and Disposition (2010-2015)
  • Acta Pharmaceutica Sinica B (2010-)
Recent Peer-Reviewed Publications (selected):
  • Zhou, X., Zhuo, X., Xie, F., Kluetzman, K., Shu, Y.-Z., Humphreys, W. G., and Ding, X.: Role of CYP2A5 in the clearance of nicotine and cotinine: insights from studies on a Cyp2a5-null mouse model. J. Pharmacol. Expt. Ther. 332, 578-587, 2010. PMC2812111
  • Conroy, J. L. 1, Fang, C. 1, Gu, J., Zeitlin, S. O., Yang, W., Yang, J., VanAlstine, M. A., Nalwalk, J. W., Albrecht, P. J., Mazurkiewicz, J. E., Snyder-Keller, A., Shan, Z., Zhang, S.-Z., Wentland, M. P., Behr, M., Knapp, B. I., Bidlack, J. M., Zuiderveld, O. P., Leurs, R., Ding, X., and Hough, L. B.: Opioids activate brain analgesic circuits through cytochrome P450/epoxygenase signaling. Nature Neurosci., 13, 284-286, 2010. PMC2828325 (1Equal contributions)
  • Weng, Y., Xie, F., Xu, L., Spink, D. C., and Ding, X.: Analysis of testosterone and dihydrotestosterone in mouse tissues by liquid chromatography–electrospray ionization–tandem mass spectrometry. Anal. Biochemistry, 402, 121–128, 2010. PMC2876209
  • Wei, Y., Zhou, X., Fang, C., Li, L., Kluetzman, K., Yang, W., Zhang, Q-Y., and Ding, X.: Generation of a mouse model with a reversible hypomorphic cytochrome P450 reductase gene: utility for tissue-specific rescue of the reductase expression, and insights from a resultant mouse model with global suppression of P450 reductase expression in extrahepatic tissues. J. Pharmacol. Expt. Ther. 334, 69-77, 2010. PMC2912046
  • Weems, J. M., Lamb, J. G., D’Agostino, J., Ding, X., and Yost, G. S.: Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and NNK. Chem. Res. Toxicol. 23, 1682–1690, 2010. PMC2981624
  • Xie, F., Zhou, X., Behr, M., Fang, C., Horii, Y., Gu, J., Kannan, K., and Ding, X.: Mechanisms of olfactory toxicity of the herbicide 2,6-dichlorobenzonitrile: essential roles of CYP2A5 and target tissue metabolic activation. Toxicol. Appl. Pharmacol. 249, 101–106, 2010. PMC2956786
  • Sheng, L. Ding, X., Ferguson, M., McCallister, M., Rhoades, R., Maguire, M., Ramesh, A., Aschner, M., Campbell, D., Levitt P., and Hood D. B.: Prenatal polycyclic aromatic hydrocarbon exposure leads to behavioral deficits and downregulation of receptor tyrosine kinase, MET. Tox. Sci. 118, 625–634, 2010. PMC2984527
  • Gonzalez, M., Sealls, W., Jesch, E. D., Brosnan, M. J., Ladunga, I., Ding, X., Black, P. N., and DiRusso, C. C.: Defining a relationship between dietary fatty acids and the cytochrome P450 system in a mouse model of fatty liver disease. Physiol. Genomics. 43:121-35, 2011. PMC3055711
  • Hough, L. B., Nalwalk, J. W., Yang, J., Conroy, J. L., VanAlstine, M. A., Yang, W., Gargano, J., Shan, Z., Zhang, S.-Z., Wentland, M. P., Phillips, J. G., Knapp, B. I., Bidlack, J. M., Zuiderveld, O. P., Leurs, R., and Ding, X.: Brain P450 epoxygenase activity is required for the antinociceptive effects of improgan, a non-opioid analgesic. Pain, 152:878–887, 2011. PMC3065546
  • Zhou, X., Wei, Y., Xie, F., Laukaitis, C. M., Karn, R. C., Kluetzman, K., Gu, J., Zhang, Q.-Y., Roberts, D. W., and Ding, X.: A novel defensive mechanism against acetaminophen toxicity in the mouse lateral nasal gland: role of CYP2A5-mediated regulation of testosterone homeostasis and salivary androgen-binding protein expression. Mol. Pharmacol. 79:710–723, 2011. PMC3063730
  • Xie, F., Zhou, X., Genter, M., Behr, M., Gu, J., and Ding, X.: The tissue-specific toxicity of methimazole in the mouse olfactory mucosa is partly mediated through target-tissue metabolic activation by CYP2A5. Drug Metab. Dispos. 39:947–951, 2011. PMC3100904
  • Zhang, X., Li, L., Ding, X., and Kaminsky, L. S.: Identification of cytochrome P450 oxidoreductase gene variants that are significantly associated with the interindividual variations in warfarin maintenance dose. Drug Metab. Dispos. 39:1433-1439, 2011. PMC3141882
  • Hollander, M. C., Zhou, X., Maier, C. R., Patterson, A. D., Ding, X., and Dennis, P. A.: A Cyp2a polymorphism predicts susceptibility to NNK-induced lung tumorigenesis in mice. Carcinogenesis 32:1279–1284, 2011. PMC3149208
  • Li, L.1, Wei, Y.1, Van Winkle, L., Zhang, Q.-Y., Zhou, X., Hu, J., Xie, F., Kluetzman, K., and Ding, X.: Generation and characterization of a Cyp2f2-null mouse and studies on the role of CYP2F2 in naphthalene-induced toxicity in the lung and nasal olfactory mucosa. . J. Pharmacol. Expt. Ther. 339:62–71, 2011. (1Equal contribution) PMC3186285
  • Court, M. H., Zhang, X., Ding, X., Yee, K., Hesse, L., and Finel, M.: Quantitative distribution of mRNAs encoding the 19 human UDP-glucuronosyltransferase enzymes in 26 adult and 3 fetal tissues. Xenobiotica, 42:266-277, 2012
  • Zhou, X., D’Agostino, J., Li, L., Moore, C. D., Yost, G. S., and Ding, X.: Respective roles of CYP2A5 and CYP2F2 in the bioactivation of 3-methylindole in mouse olfactory mucosa and lung: studies using Cyp2a5-null and Cyp2f2-null mouse models. Drug Metab. Dispos. 40:642-647, 2012. PMC3310420
  • Zhou, X., D’Agostino, J., Xie, F., and Ding, X.: Role of CYP2A5 in the bioactivation of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice. J. Pharmacol. Expt. Ther. 341:233-241, 2012. PMC3310698
  • Bai, Y., Yang, J., Zhou, X., Ding, X., Eisele, L. E., and Bai, G. Mycobacterium tuberculosis Rv3586 (DacA) is a diadenylate cyclase that converts ATP or ADP into c-di-AMP. PLoS ONE 7:e35206, 2012. PMC3328451
  • Wei, Y., Wu, H., Li, L., Liu, Z., Zhou, X., Zhang, Q.-Y., Weng, Y., D’Agostino, J., Ling, G., Zhang, X., Kluetzman, K., Yao, Y., and Ding, X.: Generation and characterization of a CYP2A13/2B6/2F1 transgenic mouse model. Drug Metab. Dispos. 40:1144–1150, 2012. PMC3362791
  • D’Agostino, J., Ding, X., Zhang, P., Jia, K., Fang, C., Zhu, Y., Spink, D., C., and Zhang, Q.-Y.: Potential biological functions of cytochrome P450 reductase-dependent enzymes in the small intestine: a novel link to the expression of the major histocompatibility complex class II genes. J. Biol. Chem. 287:17777–17788, 2012. PMC3366852
  • Lin, Y., Yao, Y., Liu, S., Wang, L., Moorthy, B., Xiong, D., Cheng, T., Ding, X., and Gu, J.: Role of mammary epithelial and stromal P450 enzymes in the clearance and metabolic activation of 7,12-dimethylbenz(a)anthracene in mice. Toxicol. Lett. 212:97-105, 2012. PMC3668431
  • Fang, C., Bolivar, V. J., Gu, J., Yang, W., Zeitlin, S. O., and Ding, X.: Neurobehavioral abnormalities in a brain-specific NADPH-cytochrome P450 reductase knockout mouse model. Neuroscience, 218:170–180, 2012. PMC3393838
  • Bardowell, S. A., Ding, X., and Parker, R. S.: Disruption of P450-mediated vitamin E hydroxylase activities alters vitamin E status in tocopherol supplemented mice and reveals extra-hepatic vitamin E metabolism. J. Lipid Res., 53:2667-76, 2012. PMC3494260 
  • Wei, Y.1, Li, L.1, Zhou, X., Zhang, Q.-Y., Dunbar, A., Liu, F., Kluetzman, K., Yang, W., and Ding, X.: Generation and characterization of a novel Cyp2a(4/5)bgs-null mouse model. Drug Metab. Dispos. 41:132–140, 2013 (1Equal contribution) PMC3533424
  • Zhang, P., Jia, K., Fang, C., Zhou, X., Ding, X., and Zhang, Q.-Y.: Dietary regulation of mouse intestinal P450 expression and drug metabolism. Drug Metab. Dispos. 41:529-35, 2013 PMC3558856
  • Lee, C., Ding, X., and Riddick, D. S.: The role of cytochrome P450-dependent metabolism in the regulation of mouse hepatic growth hormone signaling components and target genes by 3-methylcholanthrene. Drug Metab. Dispos 41:457-65, 2013 PMC3558870
  • Xie, F., D’Agostino, J., Zhou, X., and Ding, X.: Bioactivation of the nasal toxicant 2,6-dichlorobenzonitrile: an assessment of metabolic activity in human nasal mucosa and identification of indicators of exposure and potential toxicity. Chem. Res. Toxicol., 26:388-98, 2013 
  • Zhang, Y., Dong, F., Zhang, N., Cheng, H., Pang, Y., Wang, X., Xu, J., Ding, X., Cheng, T., Gu, J., and Yuan, W.: Suppression of cytochrome P450 reductase enhances long-term hematopoietic stem cell repopulation efficiency in mice. PLoS ONE, 8:e69913, 2013.
  • Yao, Y., Liu, S., Wang, Y., Yuan, W., Ding, X., Cheng, T., Shen, Q., and Gu, J.: Suppression of cytochrome P450 reductase expression promotes astrocytosis in subventricular zone in of adult mice. Neurosci. Lett., 548:84–89, 2013.
  • Xie, F., Fang, C., Schnittke, N., Schwob, J., and Ding, X.: Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: effects on stem cells and noninvolvement of the inflammatory cytokine IL-6. Toxicol. Appl. Pharmacol., 272:598–607, 2013.
  • Liu, S., Yao, Y., Lu, S., Aldous, K., Ding, X., Mei, C., and Gu, J.: The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: utility of renal specific P450 reductase knockout mouse models. Toxicol. Appl. Pharmacol., 272:230-237, 2013
  • Wu, H., Liu, Z., Ling, G., Lawrence, D. and Ding, X.: Transcriptional suppression of CYP2A13 expression by lipopolysaccharide in cultured human lung cells and the lungs of a CYP2A13-humanized mouse model. Tox. Sci., 135:476-485, 2013
  • Li, L., Jia, K., Zhou, X., McCallum, S., Hough, L. B., and Ding, X.: Impact of nicotine metabolism on nicotine’s pharmacological effects and behavioral responses: insights from a Cyp2a(4/5)bgs-null mouse. J. Pharmacol. Exp. Ther., 347:746-754, 2013
  • Lee, C., Ding, X., and Riddick, D. S.: Down-regulation of mouse hepatic cytochrome P450 3A protein by 3-methylcholanthrene does not require cytochrome P450-dependent metabolism. Drug Metab. Dispos., 41:1782-6, 2013
  • Hu, J., Li, S., Li, L., Zhou, X., Xie, F., Li, Y., and Ding, X.: Mechanisms of olfactory toxicity of naphthalene: essential roles of CYP2A5 and target-tissue metabolic activation. Drug Metab. Dispos., 42:23-7, 2014
  • Zhu, Y., Ding, X., Fang, C., and Zhang, Q.-Y.: Regulation of intestinal cytochrome P450 expression by hepatic cytochrome P450 function: impact on systemic drug exposure and possible involvement of intestinal fibroblast growth factor 15 in the regulation. Mol. Pharmacol. 85:139-47, 2014
  • Megaraj, V., Zhou, X., Xie, F., Liu, Z., Yang, W., and Ding, X.: Role of CYP2A13 in the bioactivation and lung tumorigenicity of the tobacco-specific lung procarcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: in vivo studies using a CYP2A13-humanized mouse model. Carcinogenesis, 35:131–137, 2014
  • Shen, S., Li, L., Ding, X., and Zheng, J.: Metabolism of styrene to styrene oxide and vinylphenols in cytochrome P450 2F2- and P450 2E1-knockout mouse liver and lung microsomes. Chem. Res. Toxicol., 27:27-33, 2014. 
  • Cheng, W., Zhang, R., Yao, C., Jia, K., Yang, B., Du, P., Chen, J., He, L., Liu, Z., Ding, X., and Hua, Z.: A Critical Role of FADD (Fas-Associated Protein with Death Domain) Phosphorylation in Intracellular ROS Homeostasis and Aging. Antioxidants & Redox Signaling, In Press. 
  • Megaraj, V., Fang, C., Kovulchuk, N., Zhu, Y., Ding, X., and Zhang, Q.-Y.: Role of intestinal P450 enzymes in the metabolic activation of the colon carcinogen azoxymethane in mice. Chem. Res. Toxicol., In Press.
Chapters in Books/Review Articles (selected):
  • Coon, M. J., Ding, X., Pernecky, S. J., and Vaz, A. D. N.: Cytochrome P450: Progress and Predictions. FASEB J. 6, 669-673, 1992.
  • Ding, X., and Coon, M. J.: Olfactory Cytochrome P450. in Cytochrome P-450, Handbook of Experimental Pharmacology, Volume 105 (Schenkman, J. B. and Greim, H., Eds), Chapter 22, Springer-Verlag, New York, pp. 351-361, 1993. 
  • Ding, X. and Kaminsky, L.S.: Human Extrahepatic Cytochromes P450: Function in Xenobiotic Metabolism and Tissue-Selective Chemical Toxicity in the Respiratory and Gastrointestinal Tracts. Annu. Rev. Pharmacol. Toxicol. 43, 149-173, 2003.
  • Zhang, Q.-Y. and Ding, X. The CYP2F, CYP2G and CYP2J Subfamilies. In Cytochrome P450: Role in the Metabolism and Toxicity of Drugs and Other Xenobiotics. (Ioannides C, Ed), Chapter 10, RSC Publishing, Cambridge, UK, pp. 309-353, 2008. 
  • Brusick, D., Small, M. S., Cavalieri, E. L., Chakravarti, D., Ding, X., Longfellow, D. G., Nakamura, G., Rogan, E. C., Swenberg, J. A.: Possible genotoxic modes of action for naphthalene. Regul. Toxicol. Pharmacol. 51, S43–S50, 2008.
  • Sim, S. C., Miller, W. L., Zhong, X., Arlt, W., Ogata, T., Ding, X., Wolf, C. R., Fluck, C. E., Pandey, A. V., Henderson, C. J., Porter, T. D., Daly, A. K., Nebert, D. W., and Ingelman-Sundberg, M.: Nomenclature for alleles of the cytochrome P450 oxidoreductase gene. Pharmacogenetics Genomics 19, 565–566, 2009. PMCID: PMC2753199
  • Ding, X. and Zhang, Q.-Y. Enzyme Regulation (Chapter 2), in Vol 4 (Biotransformation; Guengerich, F. P. Ed.), Comprehensive Toxicology, 2nd Edition (McQueen, C. A. Ed.), pp. 9–29, 2010, Oxford: Academic Press
  • Zhang, D., Luo, G., Ding, X., and Lu, C.: Preclinical experimental models of drug metabolism and disposition in drug discovery and development. Acta Pharmaceutica Sinica B,.2:549–561, 2012
  • Riddick, D. S., Ding, X., Wolf, C . R., Porter, T. D., Pandey, A. V., Zhang, Q.-Y., Gu, J., Finn, R. D., Ronseaux S., McLaughlin, L. A., Henderson, C. J., Zou, L., Flück, C. E.: NADPH-CYP450 oxidoreductase: Roles in physiology, pharmacology, and toxicology. Drug Metab. Dispos., 41:12–23, 2013 PMC3533425
  • Ding, X., and Xie, F.: Olfactory Mucosa: Composition, Enzymatic Localization, and Metabolism. In Handbook of Olfaction and Gustation, 3rd Edition, (Doty, R. L., Ed), Chapter 3, In press.