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CURRICULUM VITAE MANABU NUKAYA Ph.D (WORK) Department of Surgery, School of Medicine, University of Alabama-Birmingham Wallace Tumor Institute 603 1826 6th Ave. South. Birmingham, AL. 35294 Tel: (205)934-6315 Fax: (205)934-6315 E-mail; [email protected] EDUCATION AND PROFESSIONAL TRAINING 2016(Aug)-Present: Instructor Department of Surgery School of Medicine, University of Alabama-Birmingham Co-Principal Investigator; Gregory D. Kennedy, MD, PhD 2013(Apr)-2016(July): Associate Scientist Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison. Principal Investigator; Gregory D. Kennedy, MD, PhD 2009(Oct)-2013(Mar): Assistant Scientist Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison. Principal Investigator; Gregory D. Kennedy, MD, PhD 2004(Sep)-2009 (Aug): Postdoctoral Fellow McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison. Principal Investigator; Christopher A. Bradfield Ph.D 2003(Apr)-2004(Aug): Research Fellow of the Japan Society for the Promotion of Science Graduate School of Pharmaceutical Sciences. Hokkaido University. Sapporo. Hokkaido. JAPAN. Principal Investigator; Tetsuya Kamataki Ph.D 1999(Apr)-2004(Mar): Ph.D (Pharmaceutical Science) Graduate School of Pharmaceutical Sciences, Hokkaido University. Sapporo. Hokkaido. JAPAN. Title; Molecular Mechanism of Aryl Hydrocarbon Receptor-Mediated Hepatotoxicity by Polycyclic Aromatic Hydrocarbons. Adviser; Tetsuya Kamataki Ph.D 1995(Apr)-1998(Mar): B.S (Pharmaceutical Science) Department of Pharmaceutical Science, Hokkaido University, Sapporo. Hokkaido. JAPAN. RESEARCH FIELDS 1. Molecular Toxicology 2. Pharmacology 3. Molecular Biology 1 4. Mouse biology 5. Oncology TEACHING AND PROFESSIONAL EXPERIENCES (Teaching)-Research (Supervisor) 2009-2016 Teaching and supervising postdoctoral fellows, graduated students and medical students for research Rachel H. Wilson (Ph.D student, Molecular and Environmental Toxicology, 2015present) Christina W. Lee (Medical resident, Surgery, 2014-present) Melanie M. Ivancic (Postdoctoral fellow, 2014-present) Carol J. Díaz-Díaz (Ph.D student, Molecular and Environmental Toxicology, 2013present) Patrick Carney (Undergraduate student, Surgery, 2012-present) Bryant W. Megna (Undergraduate student, Surgery, 2011-14) Sean M. Ronnekleiv-Kelly (Medical resident, Surgery, 2009-2012) (Teaching)-Research (Mentor/instructor) 2014 Instructor; Teaching rotation Ph.D student for lab research (Rachel H. Wilson, (Molecular and Environmental Toxicology) 2012-2013 Mentor; Academic Staff Mentoring Program (Mentee; Mack Naber) 2012 Instructor; Teaching rotation Ph.D students for lab research (Yang Zhao, Carol J. Díaz-Díaz, Deyang Yu, (Molecular and Environmental Toxicology), Caitlin Rugani, Jordan T. Becker, (Oncology)) 2001-2004 Teaching Assistant: Teach and mentor graduate and undergraduate students (Teaching)-Class 2013 Lecture; Environmental toxicology (MET606) (Collaborations) 2014-present Co-investigator: Project I; Determine polymorphisms in AHR and members of the AHR signaling in patients with intestinal bowel disease (Dr. Murray Brilliant, the director of the Marshfield Clinic Personalized Medicine Research Project, WI). Project II; Identify novel AHR ligands produced by human microbiota (Dr. Jan-Peter van Pijkeren, University of Wisconsin-Madison, WI) Project III; Profiling intestinal microbes in AHR deletion mice. (Dr. William J, Hickey, University of Wisconsin-Madison, WI) Project IV; Examine the AHR activity of novel diindolymethane (DIM) analogs (Dr. Weiping Tang, University of Wisconsin-Madison, WI) 2011 Experiment design & analysis: Developed assay system for determination of dose response curves and EC50s of AHR-ligand induced transcriptional activity. Project I; Identification of novel AHR ligand. (Dr. Josh Mezrich, University of Wisconsin-Madison, WI) Project II; Alteration of TCDD- and benzo(a)pyrene-binding affinity within the AHR ligand binding domain by structurally driven mutagenesis. (Dr, Yongna Xing, University of Wisconsin-Madison, WI). 2 2011 Design codon-optimized expression construct for constitutively active form of AHR ( Dr. Marco Colonna, Washington University, MO) 2008-2009 Technical advisor: Generation of conditional Cyp1b1 null mouse model (Dr. Colin Jefcoate, University of Wisconsin-Madison, WI) (Reviews) 2010-2011 2012 Invited reviewer; Chemical Research in Toxicology Invited reviewer; The Journal of Biological Chemistry PROFESSIONAL MEMBERSHIPS 2002-present Member, International Society for the Study of Xenobiotics 2009-present Member (Full), Society of Toxicology 2014-present Member, American Chemical Society PROFESSIONAL CERTIFICATES 1998 Pharmacist (JAPAN) PUBLICATIONS (Peer-reviewed publications) 1. Nukaya M, Takahashi Y, Gonzalez FJ, Kamataki T. (2001) Aryl hydrocarbon receptor-mediated suppression of expression of the low-molecular-weight prekininogen gene in mice. Biochem Biophys Res Commun. 287(1):301-4. 2. Nukaya M, Takahashi Y, Gonzalez FJ, Kamataki T. (2004) Aryl Hydrocarbon Receptormediated Suppression of GH Receptor and Janus Kinase 2 expression in Mice, FEBS lett. 558, 96-100. 3. Iwano S, Nukaya M, Saito T, Asanuma F, Kamataki T. (2005) A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun. 335:220-6. 4. Iwano S, Asanuma F, Nukaya M, Saito T, Kamataki T. (2005) CYP1A1-mediated mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun. 337:708-12. 5. Hayes KR, Zastrow GM, Nukaya M, Pande K, Glover E, Maufort JP, Liss AL, Liu Y, Moran SM, Vollrath AL, Bradfield CA.(2007) Bradfield. Hepatic transcriptional networks induced by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chem Res Toxicol. 20:1573-81. 6. Nukaya M, and Bradfield CA. (2009) Conserved genomic structure of the Cyp1a1 and Cyp1a2 loci and their dioxin responsive elements cluster. Biochem. Pharmacol .77, 654-659. Review. 7. Nukaya M, Moran S, Bradfield CA. The role of the dioxin responsive elements cluster between Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. (2009) Proc. Natl. Acad. Sci. USA 106, 4923-8. * This manuscript was selected as a spotlight article in the Chemical Research in Toxicology (Chem. Res. Toxicol. 2009, 22, 968). * This manuscript was selected as 2010 Best Postdoctoral Publication Award of The Society of Toxicology. 8. Nukaya M, Lin BC, Glover E, Moran SM, Kennedy GD, Bradfield CA. (2010) The aryl hydrocarbon receptor interaction protein (AIP) is required for dioxin-induced hepatotoxicity, but not for the induction of the Cyp1a1 and Cyp1a2 genes. J. Biol. Chem. 285, 35599-605. 3 9. Nukaya M, Walisser JA, Moran SM, Kennedy GD, Bradfield CA. Bradfield. (2010) Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) in Hepatocytes is Required for Aryl Hydrocarbon Receptor-Mediated Adaptive and Toxic Responses in Liver. Toxicol. Sci.118, 55463. 10. Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M, Mantovani A, Kopan R, Bradfield CA, Newberry RD, Colonna M. (2011) AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat. Immunol.13, 144-51. 11. Xing Y, Nukaya M, Satyshur KA, Jiang L, Stanevich V, Korkmaz EN, Burdette L, Kennedy GD, Cui Q, Bradfield CA.(2012) Identification of the ah-receptor structural determinants for ligand preferences. Toxicol. Sci.129, 86-97. 12. Mezrich JD, Nguyen LP, Kennedy GD, Nukaya M, Fechner JH, Zhang X, Xing Y, Bradfield CA. (2012) SU5416, a VEGF Receptor Inhibitor and Ligand of the AHR, Represents a New Alternative for Immunomodulation. PLoS One 7, e44547. 13. Kennedy GD, Nukaya M, Moran SM, Glover E, Weinberg S, Balbo S, Hecht SS, Pitot HC, Drinkwater NR, Bradfield CA. (2014) Liver tumor promotion by 2,3,7,8-tetrachlorodibenzo-pdioxin is dependent on the aryl hydrocarbon receptor and TNF/IL-1 receptors. Toxicol. Sci.140, 135-43. 14. Ronnekleiv-Kelly SM, Nukaya M, Díaz-Díaz CJ, Megna BW, Carney PR, Geiger PG, Kennedy GD. (2016) Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells. Cancer Lett. 370, 91-9. 15. Díaz-Díaz CJ, Ronnekleiv-Kelly SM, Nukaya M, Geiger PG, Balbo S, Dator R, Megna BW, Carney PR, Bradfield CA, Kennedy GD. (2016) The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse. Ann. Surg. 264, 429-36. 16. Megna BW, Carney PR, Nukaya M, Geiger P, Kennedy GD. (2016) Indole-3-carbinol induces tumor cell death: function follows form. J. Surg. Res. 204, 47-54. (Electronic publication in GenBank) 1. Nukaya M, and Bradfield CA. Mus musculus strain 129/Sv cytochrome P450 family 1 subfamily a polypeptide 2 (Cyp1a2) and cytochrome P450 family 1 subfamily a polypeptide 1 (Cyp1a1) genes, complete cds. GenBanK; FJ392393. 2008. AWARDS AND GRANTS 1. 2. 3. 4. Japan Students Services Organization: Student Scholarship (1999-2003, JAPAN) ITO Medical Science Foundation: Travel Award (2001, JAPAN) 21st COE Project Grant: Travel Award (2002, JAPAN) 30th Annual Meeting of The Japanese Society of Toxicology: Best Poster Presentation Award (2003, JAPAN) 5. Japan Society for the Promotion of Science: Research Fellowship Grant for Young Scientists (2003-2004, JAPAN). (Salary; 2,000,000-3,600,000 JPY x 2yrs, Research fund; 1,500,000 JPY x 2yrs) 6. 2010 Best Postdoctoral Publication Award of The Society of Toxicology (2010, USA) MEETING PRSENTATIONS (JAPAN) 1. 15th Annual Meeting of the Japanese Society for the Study of Xenobiotics (2000, talk) Fukuoka, JAPAN 4 2. 3. 4. 5. 6. 7. 8. 9. 10. 23rd Annual Meeting of the Molecular Biology Society of Japan (2000, poster) Kobe, JAPAN 121st Annual Meeting of the Pharmaceutical Society of Japan (2001, poster) Sapporo, JAPAN. 28th Annual Meeting of the Japanese Society of Toxicology (2001, selected talk) Tokyo, JAPAN. 60th Annual Meeting of Japan Cancer Association. (2001, talk) Yokohama, JAPAN 16th Annual Meeting of the Japanese Society for the Study of Xenobiotics (2001, talk) Kobe, JAPAN 29th Annual Meeting of the Japanese Society of Toxicology (2002, poster) Nagoya, JAPAN. 25th Annual Meeting of the Molecular Biology Society of Japan (2002, poster) Yokohama, JAPAN 123rd Annual Meeting of the Pharmaceutical Society of Japan (2003, poster) Nagasaki, JAPAN. 30th Annual Meeting of the Japanese Society of Toxicology (2003, poster+talk) kanagawa, JAPAN. (USA) 11. 11th Annual Meeting of North American International Society for the Study of Xenobiotics (2002, poster) Orlando, USA. 12. 2005 Cancer Biology Student/Postdoc Seminar Series Meeting (2005, talk) Madison WI, USA. 13. 2006 Cancer Biology Student/Postdoc Seminar Series Meeting (2006, talk) Madison WI, USA. 14. 2007 Cancer Biology Student/Postdoc Seminar Series Meeting (2007, talk) Madison WI, USA. 15. 2008 Cancer Biology Student/Postdoc Seminar Series Meeting (2008, talk) Madison WI, USA. 16. 15th Annual Meeting of North American International Society for the Study of Xenobiotics (2008, poster) San Diego CA, USA. 17. University of Wisconsin-Milwaukee (2009, Invited talk). Milwaukee WI, USA. 18. 2011 Second Annual Research Summit (2011, Poster+talk), Verona WI, USA. 19. 2012 Third Annual Research Summit (2012, Poster+talk), Verona WI, USA. 20. 31st Summer Symposium in Molecular Biology (2012, Poster) State college, PA. 21. 2013 4th Annual Research Summit (2013, Poster+talk), Madison WI, USA. (INTERNATIONAL) 21. 9th International Congress of Toxicology (2001 poster) Brisbane, AUSTRALIA. 22. 14th Annual Meeting of International Symposium on Microsome and Drug Oxidations (2002, poster) Sapporo, Japan. 5