OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Guo, Grace L. eRA COMMONS USER NAME: gracelguo

POSITION TITLE: Associate Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) Completion DEGREE INSTITUTION AND LOCATION Date FIELD OF STUDY (if applicable) MM/YYYY West China University of Medical Sciences, China Bachelor of 1987-1993 Preventive Medicine Medicine/Medicine West China University of Medical Sciences, China MPH 1993-1995 Occupational Medicine University of Arkansas Medical Science, Little M.S. 1995-1997 Immunology Rock, AR University of Kansas Medical Center, Kansas City, Pharmacology & Ph.D. 1997-2001 KS Toxicology Laboratory of Metabolism, CCR, NCI, NIH, Nuclear Receptor and Post-doc 2001-2004 Bethesda, MD Metabolism

A. Personal statement.

For the past two decades, I have devoted my research to nuclear receptors and signaling pathways that are critical for liver homeostasis and metabolism, including farnesoid X receptor (FXR), pregnane X receptor, constitutive androstane receptor and fibroblast growth factor 15/19 (FGF15/19). Our focused research findings include providing a paradigm shift in understanding the cellular and molecular mechanism by which tissue-specific FXR functions to regulate bile acid homeostasis, drug metabolism and transport, non-alcoholic hepatosteatosis, liver and colon carcinogenesis, and liver regeneration. In addition, we are the first laboratory to determine the genome-wide FXR binding in a tissue-specific manner. As the PI, I have the expertise, leadership and motivation necessary to carry out the proposed works by state-of-the-art and compensatory approaches. I have a broad background in the functional characterization of liver and GI diseases in animal models, lipid homeostasis, drug metabolism and transport, as well as their regulation by nuclear hormone receptors and cell signaling pathways. I have published 80 peer-reviewed research and review articles on nuclear receptors and their regulation of liver and intestine functions. I have collaborated and helped scientists across the world to determine FXR and FGF15 function in regulating bile acid and lipid homeostasis. As the PI or Co-I on several NIH funding, I laid the ground work by determining the role of intestinal FXR in regulating liver functions. I addition, I have successfully administered the projects, collaborated with other scientists, and remained productive. I have experience in constructing research plans, following timeline, and managing budget. I have devoted a great amount of effort in serving the scientific community, including reviewing manuscripts and federal and foundation grants. By direct and indirect supervising more than 40 students and fellows, I have established as a dedicated teacher in high education. In summary, I have a demonstrated record of successful and productive research in determining nuclear receptors in gut-liver cross talk and liver functions.

B. Positions and Honors

Positions 1993-1995 Resident, Hospital of Occupational Medicine, West China University of Medical Sciences, Chengdu, China 1995-1997 Teaching Assistant, University of Arkansas Medical Science 1997-2001 Teaching Assistant, University of Kansas Medical Center 2001-2002 Visiting Fellow, National Cancer Institute, National Institute of Health, Bethesda, MD 2002-2004 Research Fellow, National Cancer Institute, National Institute of Health, Bethesda, MD 2004-2009 Assistant Professor, Department of Pharmacology and Toxicology, University of Kansas Medical Center, Kansas City, KS 2010-2012 Associate Professor, Department of Pharmacology and Toxicology, University of Kansas Medical Center, Kansas City, KS 2012-present Associate Professor, Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ Full member for New Jersey Cancer Center and Rutgers University Lipid Center 2014-present Research Scientist, GI Laboratory, VA Medical Center, East Orange, NJ

Honors 1993 Graduated with the highest honor, West China University of Medical Sciences (current Sichuan University), China 2001 First place in Oral Presentation, Student Annual Research Forum, University of Kansas Medical Center 2001 Graduate with honor for the PhD degree 2005 BIRCWH scholarship for study of women’s health 2008 All-around winner, annual KUMC Cancer Center Symposium 2009 Best poster, junior faculty, annual KUMC liver Center Symposium 2009 Presidential poster award, annual AASLD meeting 2010 Presidential poster award, annual AASLD meeting 2011 Presidential poster award, annual AASLD meeting 2012 Presidential poster award, annual AASLD meeting (2)

Other Experience and Professional Memberships

1999-present American Society of Pharmacology and Experimental Therapeutics, Member 1999-present American Society of Toxicology, Member 1999-present Sigma Xi, Member (President-elect and President, Chapter #260 – 2009-2010) 2000-present American Association of the Study of Liver Diseases, Member 2012-present American Society of Physiology

Editorial board member and Ad hoc journal reviewers (2001-): editor---Special Issue of Acta Pharmaceutica Sinica B, editorial board---Molecular Pharmacology, Ad hoc reviewer---JCI, Hepatology, JBC, Advanced drug delivery, American Journal of Pathology, Arteriosclerosis, Thrombosis and Vascular Biology, British Journal of Pharmacology, Carcinogenesis, Drug Metabolism and Disposition; others---F1000PRIME (2010 to present)

Grant review (Federal): VA GAST (2013 to present), NIDDK fellowship (2013 to present), HBPP (2015 ad hoc), NIDDK SBIR (2014), NCI PO1 (2013), NCI R03/R21 (2013 and 2014), Italian NIH Grants (2010- present), AACP (2014)

C. Contribution to Science (from more than 80 publications)

First in establishment of nuclear receptor-mediated transcriptional regulation of hepatic organic anion uptake transporters. Induction of drug metabolizing enzymes or transporters is critical in drug disposition and drug-chemical interaction. My graduate work showed, for the first time, the uptake transporters in the livers are transcriptional targets of nuclear receptors. 1. Guo GL and Klaassen CD: Protein kinase C suppresses rat organic anion transporting polypeptide 1- and 2-mediated uptake. J Pharmacol Exp Ther, 299: 551-557, 2001. PMC Journal – In Process 2. Guo GL, Staudinger J, Ogura K and Klaassen CD: Induction of the rat organic anion transporting polypeptide 2 by pregnenolone-16-carbonitrile is via interaction with the pregnane-x-receptor. Mol Pharmacol, 61:832-839, 2002. PMC Journal – In Process 3. Guo GL, Choudhuri S, and Klaassen CD: induction profile of rat organic anion transporting polypeptide 2 (oatp2) by prototypical microsomal enzyme inducers that act through ligands-activated transcription factor pathways. J Pharmacol Exp Ther, 300:206-212, 2002. PMC Journal – In Process 4. Guo GL, Johnson DR and Klaassen CD: Expression and induction by pregnenolone-16-carbonitrile (PCN) of rat organic anion transporting polypeptide 2 (oatp2) in the liver during postnatal development, Drug Metab Dispos, 30:283-288, 2002. PMC Journal – In Process

Establishing nuclear receptor cross-talk in regulation of bile acid homeostasis. Cholestasis is a severe liver pathology and there is no current effective treatment for cholestasis. To understand the molecular mechanisms in reducing liver injury under cholestasis will help to discover novel therapeutic agents in reducing cholestasis. 5. Guo GL, Lambert G, Negishi M, Ward J, Brewer HB Jr, Kliewer SA, Gonzalez FJ, Sinal CJ: Complementary roles of farnesoid x receptor, pregnane x receptor, and constitutive androstane receptor in protection against bile acid toxicity. J Biol Chem. 278:45062-45071, 2003. PMC Journal – In Process 6. Lambert G, Amar MJ, Guo GL, Brewer HB Jr, Gonzalez FJ, Sinal CJ: The farnesoid X receptor is an essential regulator of cholesterol homeostasis. J Biol Chem 278:2563-70, 2003 PMC Journal – In Process 7. Jia Y, Guo GL, Surapureddi S, Sarkar J, Qi C, Guo D, Xia J, Kashireddi P, Yu A, Cho YW, Rao S, Kemper B, Ge K, Gonzalez FJ, Reddy JK: Transcription coactivator peroxisome proliferators-activated receptor-binding protein/mediator 1 deficiency abrogates acetaminophen hepatotoxicity. Proc Natl Acad Sci USA. 2005, 102:12531-6. PMCID: PMC1187948

Pioneered in providing paradigm shift in understanding the critical role of intestinal pathways in regulating hepatic bile acid homeostasis and liver functions. The discovery in identifying a novel pathway that is critical in feedback inhibiting bile acid synthesis provide novel insight into physiology, as well as new pathways to treat cholestasis and hypercholesterolemia. 8. Kim I, Ahn SH, Inagaki T, Choi M, Ito S, Guo GL, Kliewer SA, Gonzalez FL. Differential regulation of bile acid homeostasis by the farnesoid x receptor in liver and intestine. J Lipid Res, 2007, 48:2664-72. PMC Journal – In Process 9. Kong B, Wang L, Chiang JY, Zhang Y, Klaassen CD, Guo GL. Mechanism of tissue-specific farnesoid x receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology 2012. 56:1034. PMCID:PMC3390456 10. Kong B, Huang J, Zhu Y, Li G, Williams J, Shen S, Aleksunes A, Richardson J, Apte U, Rudnick DA, Guo GL. FGF15 deficiency in mice impairs liver regeneration. Am J Physiol Gastrointest Liver 2014 May 15;306(10):G893-902. PMCID: PMC4024724 11. Kong B, Huang J, Zhu Y, Li G, Williams J, Shen S, Aleksunes A, Richardson J, Apte U, Rudnick DA, Guo GL. FGF15 deficiency in mice impairs liver regeneration. Am J Physiol Gastrointest Liver 2014 May 15;306(10):G893-902. PMCID: PMC4024724

First in publishing critical roles of FXR in pathogenesis of metabolic syndrome-related diseases in animal models (atherosclerosis, non-alcoholic fatty liver disease, colon cancer). Our work provides the first foundation in establishing FXR as a target to treat NASH. 12. Guo GL, Santamarina-Fojo S, Akiyama TE, Amar MJA, Paigen BJ, Brewer HB Jr, Gonzalez FJ: Effect of FXR in foam-cell formation and atherosclerosis development. Biochim Biophys Acta (BBA) - Molecular and Cell Biology of Lipids, 2006, 1761:1401-9. PMCID: PMC1751860 13. Kong B, Luyendyk JP, Tawfik O, Guo GL. FXR-deficiency induces non-alhocolic steatohepatitis in LDLr-knockout mie fed a high-fat diet. J Pharmacol Exp Ther. 2009, 328:116-22. PMCID:PMC2685903 14. Maran RR, Thomas A, Roth M, Sheng Z, Esterly N, Pinson D, Gao X, Zhang Y, Ganapathy V, Gonzalez FJ, Guo GL. FXR-deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J Pharmacol Exp Ther. 2009, 328:469-77. PMCID: PMC2682273 15. Li G, Kong B, Zhu Y, Zhan L, Williams J, Tawfik O, Luyandyk JP, Wang L, Guo GL. Mechanisms of STAT3 activation in the liver of FXR knockout mice. Am J Physiol Gastrointest Liver Physiol. 2013, 305(11);G829-37. PMCID: PMC3882431

First in publishing genome-wide study of FXR for tissue-specific gene regulation and species difference. Our group provides the first evidence of genome-wide biding of FXR in the liver and intestine, which not only provides novel insights into the pathways by which FXR regulates liver and energy homeostasis, but also expending the molecular mechanism by which FXR regulates genes expression at the transcription level. 16. Thomas A, Hart S, Kong B, Fang J, Zhong X, and Guo GL. Genome-wide tissue specific FXR binding in mouse liver and intestine. Hepatology 2010. 51(4):1410-9. PMC Journal – In Process 17. Williams JA, Thomas AM, Li G, Kong B, Zhan L, Inaba Y, Xie W, Ding WX, Guo GL. Tissue-specific induction of p62/Sqstm1 by farnesoid X receptor. PLoS One. 2012;7(8):e43961. doi: 10.1371/journal.pone.0043961. PMCID: PMC3428273 18. Li G, Lin W, Araya JJ, Chen TT, Timmermann BN, Guo GL. A tea cathechin, epigallocatechin-3-gallate, is a unique modulator of the farnesoid X receptor.. Toxicol Appl Pharmacol.2012. 258(1):268-74. PMCID: PMC3259191 19. Zhan L, Guo GL. Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes, PLoS One, 9(9):e105930,2014. PMCID:PMC4157742

Complete List of Published Work in MyBibliography available in Pubmed: http://www.ncbi.nlm.nih.gov/sites/myncbi/grace.guo.1/bibliography/40679131/public/?sort=date&direction =descending

Research Support

Ongoing Research Support R01GM104037-01, Guo, Grace (PI) 7/01/2013 – 6/30/2017 NIH/NIGMS Title: Gut bile acids, Fxr, & Fgf15 in total parenteral nutrition-associated cholestasis This project will determine the contribution of gut FXR pathways disruption to the development of total parenteral nutrition-associated cholestasis

Busch grant (Co-PI with Naureen Momone): 9/01/2015-8/31/2017 Rutgers University research pilot grant Title: Neonatal liver disorders and FGF19 This proposal will determine the human FGF19 levels in neonatal babies and its association with cholestasis

HD082965 (Co-mentor; PI: Jamie Moscovita; F31) Title: Genetic and pharmacological regulation of hepatic and ileal FXR during pregnancy

This proposal is to serve as a co-sponsor to mentor graduate student for the effect of pregnancy on FXR expression during pregnancy and its relationship with intrahepatic cholestasis during pregnancy

Completed Research Support

R01DK081343-02S1 (PI: Guo, Grace) 01/02/2010-31/1/2011 NIDDK/NIH, Administrative supplement for R01 DK081343-02

R01 DK081343-02, Guo, Grace (PI) 01/06/2008-31/05/2013 NIDDK/NIH Title: Tissue specific mechanism of FXR in suppressing bile-acid synthesis This project is to determine the tissue-specific roles of FXR and its regulated pathways in regulating bile acid synthesis in the liver.

R56DK090036-01A1, Guo, Grace (PI) 10/01/2011 – 09/30/2013 NIDDK/NIH Title: FXR, nuclear receptors, and transcriptional regulation of liver homeostasis This is a bridging grant to obtain genome-wide FXR binding in human livers.