CURRICULUM VITAE

NAME: Shi, Geng-Xian

TITLE: Assistant Researcher

PHONE: 808-***-**** (Cell)

EMAIL: acw5zb@r.postjobfree.com

A.Personal Statement

I am current an Assistant Research at the NCI-designated University of Hawaii Cancer Center. I have a multidisciplinary background, including immunology, molecular and cellular biology, neurosciences, cancer biology and pharmacology. I have exceptional ability to conceive and perform innovative biomedical research, which has been evidenced by my documented productivity and creativity. I have published 29 papers in peer-reviewed international journals, acting as first author in 15 articles and as senior correspondence author in 5 publications. I have great expertise in signal transduction, molecular and cellular biology. I have conducted mechanistic research to understand the pathophysiological role for various proteins and signal transduction pathways in human immune diseases, neurodegenerative disorders and cancer. Deciphering the pathophysiological mechanisms is of important for the development of novel therapeutic strategies for the effective and/or personalized treatment.

My expertise in biomedical research began to develop under my Ph.D. mentor, Liping Zhu at the Peking Union Medical College in 1997, and John H. Kehrl, M.D., Ph.D., at the National Institute of Allergy and Infectious Diseases in 2000, and continued under the guidance of Douglas A. Andres, Ph.D. at the University of Kentucky. I have also carried out collaborations with a broad array of international scientists including Dr. Lein at University of California at Davis, Drs. Berger and Meyerson in the Broad Institute, Dr. Han in the Scripps Research Institute and Dr. Rehmann in the Netherlands.

My research has (1) identified a novel cell surface protein key to the susceptibility of lymphocytes to death, and to cancer metastasis; (2) demonstrated that RGS proteins provide stop signal for lymphocyte trafficking during immune responses; (3) established the Rit subfamily of small GTPases as regulators key to neuronal differentiation and survival in the central nerve system, and defined their protective role in neurodegenerative disorders and their RASopathy in human cancers and Noonan syndrome; (4) elucidated the mechanisms for RSKs, R-Ras, Bit1, PEA15 and RasGRP1 in tumorigenesis of human cancers.

Now, I wish to utilize these expertise to devote to the research and development of therapeutics or diagnosis of human diseases in industrial fields. Because of my background, experience and achievements, I am confident in that I am well prepared to continue my career in industrial, and I will make out great contribution.

B.Education and Postdoctoral Training

INSTITUTION AND LOCATION

DEGREE

Completion Date

FIELD OF STUDY

Nanjing University of Traditional Chinese Medicine, Nanjing, China

B.S.

07/1984

Pharmacy & Pharmacology

Peking Union Medical College, Beijing, China

M.S.

07/1991

Biotechnology & Pharmacology

Peking Union Medical College, Beijing, China

Ph.D.

07/2000

Molecular Biology & Immunology

National Institute of Allergy and Infectious Diseases, Bethesda, MD

Postdoc

08/2002

Molecular Biology & Immunology

University of Kentucky College of Medicine, Lexington, KY

Postdoc

11/2004

Molecular Biology & Neurosciences

C.Positions and Honors

Positions and Employment

1984-1988 Research Associate, Department of Pharmacology, Nanjing College of Traditional Chinese Medicine, Advisor: Quan Zhu

1988-1991 Graduate Student, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Mentor: Prof. Si-Ying Li

1991-1993 Research Assistant Professor, Institute of Medicinal Biotechnology, CAMS and PUMC

1993-1997 Project Manager, Peking University Founder Group, Ltd, Beijing

1997-2000 Ph. D. Degree Candidate, Department of Immunology, Institute of Basic Medical Sciences, CAMS and PUMC, Mentor: Dr. Li-Ping Zhu

2000-2002 Visiting Fellow, Laboratory of Immunoregulation (LIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, Advisor: Dr. John H. Kehrl

2002-2004 Postdoctoral Fellow, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Advisor: Dr. Douglas A. Andres

2004-2006 Scientist II, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, Advisor: Dr. Douglas A. Andres

2007-2013 Research Assistant Professor, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky

2013- Assistant Researcher, University of Hawaii Cancer Center, Honolulu, Hawaii

Honors and Awards

1998 The Best Experimental Record awarded by the Institute of Basic Medical Sciences, CAMS

1999 Outstanding Scientific Presentation, awarded by the China Association of Immunology, November, 1999, Beijing

1999, 2000 Outstanding Ph. D. candidate, awarded by the Graduate School, PUMC, Beijing

2000 Outstanding Graduated Ph. D., awarded by Graduate School, PUMC, Beijing

2000-2002 Visiting Fellowship, Fogarty International Center, National Institutes of Health, Bethesda 20892, Maryland

2004 Patent - “Adeno-associated virus (AAV) based gene delivery system”, by China Bureau of Patent, Patent Number, ZL-01118841.3

D.Contributions to Biomedical Research (*, correspondence senior author)

1.Modification of protein glycosylation affects cell behavior (1997-2000). We have isolated a novel 6A8 cDNA encoding a novel cell surface protein of α-mannosidase (Man6A8). Overexpression of Man6A8 reduces cell surface glycan complexity. Inhibition of Man6A8 expression changes the susceptibility of immune cells to death, and reduces the metastasis of human nasopharyngeal carcinoma to lung.

1) Li B, Wang ZZ, Ma FR, Shi GX, Zhang LX, Zeng X, Liu Y, Zhao FT and Zhu LP (2000) Cloning, expression and characterization of a cDNA (6A8) encoding a novel human alpha-mannosidase. Eu J Biochem, 267 : 7176-82

2)Shi G, Jin Y, Wang Z, Cui W, Liu Y, Wang X and Zhu L (2001) Resistance of SKW6 cell to apoptosis induction with anti-Fas antibody upon transduction of a reverse fragment to a cDNA encoding human 6A8 alpha-mannosidase. Sci China (Series C) Life Sci, 44 : 365-72

3)Shi GX, Wang Y, Liu Y, Zhao FT and Zhu LP (2001) Long-term expression of a transferred gene in Epstein-Barr virus transformed human B cells. Scand J Immunol, 54 : 265-72

4)Shi GX, Liu Y, Li L and Zhu LP (2002) Inhibition of 6A8 alpha-mannosidase causes oncosis-like death of BJAB cells. Cell Mol Biol, 48 On-line publication: OL369-77

5)Yue W, Jin YL, Shi GX, Liu Y, Gao Y, Zhao FT and Zhu LP (2004) Suppression of 6A8 alpha-mannosidase gene expression reduced the potentiality of growth and metastasis of human nasopharyngeal carcinoma. Intl J Cancer, 108 (2) : 189-95

6)Jin YL, Yue W, Shi GX, Liu Y, Zhao FT and Zhu LP (2005) Inhibition of 6A8 alpha-mannosidase gene expression resulted in telomere length shortening in nasopharyngeal carcinoma cell CNE-2L2. Cancer Letters, 218 (2) : 229-34

2.Regulator of G protein signaling (RGS) proteins regulate chemokine signaling and immune cell trafficking (2000-2002). Normal lymphoid tissue development and function depend upon directed cell migration. This process is guided by chemokine signal through cell surface receptors that couple to heterotrimeric G proteins, which are in turn subjected to regulation by RGS proteins including RGS13 and RGS18. RGS proteins provide stop signals for chemoattractant responses, and assist immune cells in making decision in trafficking.

1)Shi GX, Harrison K, Wilson GL, Moratz C and Kehrl JH (2002) RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13. J Immunol, 169 (5) : 2507-15

2)Shi GX, Harrison K, Han SB, Moratz C and Kehrl JH (2004) Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: implications for G protein-coupled receptor signaling. Journal of Immunology, 172 (9) : 5175-84, PMID: 15100254

3.Rit subfamily of small GTPases are key regulators in neuronal differentiation and survival (2002-2013). My studies have demonstrated that Rit and Rin GTPases play critical role in neuronal differentiation and survival. They act as intracellular sensors to rely a variety of signaling cascades in a distinctive manner. Rit proteins contributes to both nerve growth factor- and pituitary adenylyl cyclase-activating polypeptide 38 (PACAP38)-induced neuronal differentiation. Rit and Rin regulate both ERK and p38 mitogen-activated protein kinases. My studies have revealed a critical role for Rit in controlling p38 activity and confers cellular resistance to diverse environmental stresses. We also identified the RASophathy role for Rit in human cancers and Noonan syndrome.

1)Shi GX and Andres DA (2005) Rit contributes to nerve growth factor-induced neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades, Mol Cell Biol, 25(2) : 830-46

2)Shi GX, Han J and Andres DA (2005) Rin GTPase couples nerve growth factor signaling to p38 and b-Raf/ERK pathways to promote neuronal differentiation. J Biol Chem, 280 : 37599-609

3)Shi GX, Rehmann H and Andres DA (2006) A novel cyclic AMP-dependent Epac-Rit signaling pathway contributes to PACAP38-mediated neuronal differentiation. Mol Cell Biol, 26 (23) : 9136-47

4)Lein PJ, Guo X, Shi GX, Moholt-Siebert M and Andres DA (2007) The novel GTPase Rit differentially regulates axonal and dendritic growth. J Neurosc, 27 (17) : 4725-36

5)Shi GX*, Jin L and Andres DA (2008) Pituitary adenylate cyclase-activating polypeptide 38-mediated Rin activation requires Src and contributes to the regulation of HSP27 signaling during neuronal differentiation. Mol Cell Biol, 28 (16), 4940-51

6)Andres DA, Shi GX, Bruun D, Barnhart C and Lein PJ (2008) Rit signaling contributes to interferon-gamma-induced dendritic retraction via p38 mitogen-activated protein kinase activation. J Neurochem, 107 : 1436-47

7)Shi GX*, Jin L, and Andres DA* (2010) Src-dependent TrkA transactivation is required for PACAP38-mediated Rit activation and neuronal differentiation. Mol Biol of the Cell, 21 : 1597-608

8)Shi GX*, Jin L. and Andres DA (2011) A Rit GTPase-p38 mitogen-activated protein kinase survival pathway confers resistance to cellular stress, Mol Cell Biol, 31(10) : 1938-48

9)Shi GX*, Cai W and Andres DA (2012) Rit-mediated stress resistance involves a p38-mitogen- and stress-activated protein kinase 1 (MSK1)-dependent cAMP response element-binding protein (CREB) activation cascade. J Biol Chem; 287(47) : 39859-68

10)Berger AH, Imielinski M, Duke F, Wala J, Kaplan N, Shi GX, Andres DA and Meyerson M (2014) Oncogenic RIT1 mutations in lung adenocarcinoma, Oncogene, 33(35) : 4418-23

11)Koenighofer M, Hung CY, McCauley JL, Back EJ, Mihalek I, Gripp KW, Sol-Church K, Rusconi P, Zhang Z, Shi GX, Andres DA and Bodamer O (2016) Mutations in RIT1 causes Noonan syndrome – additional functional evidence and expanding the clinical phenotype, Clin Genetics, 89(3) : 359-66

4.Elucidation of signaling mechanism contributing to tumor cell migration and invasion (2013-present). Tumor invasion is a multistep cellular process and guided orchestrally by the diversity of intracellular signaling and environmental cues. My studies uncovered the mechanisms for various protein effectors that coordinate cell migration and vascular-endothelial barrier function in tumor invasion.

1)Shi GX, Jin L, Matter ML and Ramos JW (2016) RSK2 provokes invasive signaling through LARG-dependent activation of Rho GTPases, in preparation

2)Shi GX, Anastasiadis P, Ramos JW and Matter ML (2016) R-Ras maintains endothelial integrity through blockade of Src-FAK-VE-cadherin signaling, in preparation

3)Shi GX, Ramos JW and Matter ML (2016) Bit1 deletion mutation reduces focal adhesion turnover, in preparation

4)Jin L, Shi GX, Ramos JW and Ji J (2016) JNK signaling is essential for RasGRP1-mediated cellular resistance of keratinocytes to UVA exposure, in preparation

5)Caliva MJ, Shi GX, Young-Robbins S, Valmiki MG, Opoku-Ansah J, Matter ML, Grimes ML and Ramos JW (2016) PEA-15 is an endosomal microtubule-binding phosphoprotein that regulates alpha5beta1 integrin recycling, J Cell Sc, under revision

6)de la Vega M, Shi GX, Ramos JW and Matter ML: Trabid compromises Wnt signaling through deubiquitination of TLE1, in preparation

Complete List of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/sites/myncbi/1V75as9xgqHAY/bibliography/48758997/public/?sort=date&direction=ascending

E.References

Joe W. Ramos, Ph. D. and Professor, Interim Associate Director, University of Hawaii Cancer Center, University of Hawaii at Manoa, 701 Ilalo Street, Honolulu, HI 96813, phone: 808-***-****; email: acw5zb@r.postjobfree.com

Douglas A. Andres, Ph. D. and Professor, Chair, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 South Limestone Street, Lexington, KY 40536, phone: 859-***-****; email: acw5zb@r.postjobfree.com

Haining Zhu, Ph. D. and Professor, Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 Limestone Street, Lexington, KY 40536, phone: 859-***-****; email: acw5zb@r.postjobfree.com

Michelle L. Matter, Ph. D. and Associate Professor, Natural Products and Experimental Therapeutics, University of Hawaii Cancer Center, University of Hawaii at Manoa, 701 Ilalo Street, Rm. 456, Honolulu, HI 96813, phone: 808-***-****; email: acw5zb@r.postjobfree.com

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