Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 1

Contents

Cover letter 1 Curriculum Vitae 3 Reference Contact List 10 Teaching Statement 10 Statement of Research Interests: 13 Cover letter

8-25-2015

Dear Human Recourse and Search Committee,

Please accept my application for a position of Project Manager for Clincial RD or Science Officer or Clinical Science Associate, research scientist, medical scientist or medical science liaison (MSL) or professor at your company.

I am a clinician (with license in China only), teacher, molecular biologist, research scientist and human geneticist. Now I am working as a Tenure Track faculty at Department of Pediatrics, Texas Tech University Health Science Center (TTUHSC), TX, USA. I am very interested in teaching and developing a clinical and translation research programs with a focus on neuroscience, personalized medicine, human health, human molecular genetics, pharmacogenetics/pharmacogenomics, and nutrigenetics/nutrigenomics of human complex diseases (such as neuropsychiatric disorders, diabetes, cardiovascular diseases, or cancer) in collaboration with people from various disciplines at Alberta health Services. I received my M.D. (Bachelor degree) and Master degree at Harbin Medical University, China and I received my Ph.D. in diabetes and neuroscience, at the Karolinska Institute in Stockholm Sweden. I have 6-year Postdoctoral experience in clinical and translation research. My career goal is to work in the clinical research and development field at an industry setting. I am very interested and have gained extensive teaching and working experience in health and medical education, clinical research, health science, biomedical science and translational research for human diseases (e.g.,, neuropsychiatric disorders, cancers, autoimmune diseases). I have gained extensive teaching and working experience in the field of genetic epidemiology, human molecular biology, genetics/genomics, human molecular biology, genetics of neuropsychiatric disorders, human population genetics, human health, and nutrigenetics since 1992. I have responsible for clinical research, basic research and teaching courses. Major achievement during these years are: identified causative mutations and/or risk variants/genes for 21-hydroxylase deficiency (Xu C et al., 1994), type 2 diabetes, multiple sclerosis (Xu et al., 1998, 1999, 2001), attention-deficit/hyperactivity disorder (Xu C et al, 2001), Tourettes syndrome, tobacco dependency (Xu et al., 2002, 2003), bipolar disorder (BD) (Xu et al., 2005-2013), rheumatoid arthritis (RA) (Xu et al., 2009), primary biliary cirrhosis (Xu et al., NEJM 2009, Nature Genetics 2010), schizophrenia (SC, Xu 2013) and Alzheimer disease (Xu 2013). I enjoy teaching, both in the classroom and in personal interactions with students and I view teaching as an important component of my career. Teaching gives me the opportunity to share my knowledge with students while discussions with students also enhance my understanding of the concept (for details of my teaching experience, philosophy and interests, please see my CV). I teach human genetics, genomic Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 2 diagnosis, pharmacogenetics/pharmacogenomics for our clinicians, residents and medical students. I teach medical genetics, clinical genetics, human molecular genetics, and nutrigenetics for the medical students

(U10CP8), clinical residents/fellows. I also teach immunology (GBSE5225) and Advanced Human Genetics (GBSE5221) for the graduate students at the TTUHSC. My current research projects and teaching include health promotion for human disorders, environmental factor identifications.

In addition, I have competency and successful experience as a MSL, medical scientist. I have ability to coach and mentor field medical colleagues. As a clinician, I have advanced knowledge of clinical medicine, disease management, and medical research. I have working experience in clinical research in a number of human diseases, such as diabetes, multiple sclerosis, psychiatric disorders, and autoimmune diseases. I have ability to synthesize complex scientific information and analyze it within strategic and regulatory settings.

I have working experience of using IT tools and interface effectively with a variety of technical platforms. I have strong personal integrity, and customer focus, excellent interpersonal communication, negotiation and advanced presentation skills.

In addition, I have working experience in clinical research in a number of human diseases, such as diabetes, multiple sclerosis, psychiatric disorders, and autoimmune diseases. I have included one of my application packets

1. My cover letter

2. my CV, reference contact list, teaching statement, and outline of one of my research interests: biomarker identification for neurological diseases

3. Selected Reprints.

I believe that based on my educational background, research abilities, teaching experience, work experiences, and translational research interests, I can make a significant contribution to your company. I am a hard-worker, quick learner, and self-motivated individual. I would be happy to send you additional materials such as reprints of my publications. I look forward to discussing your needs and my qualifications as soon as possible. I would be happy to arrange three letters of reference if the contacted for first interview. Thank you very much for your time and consideration. Sincerely yours,

Dr. Chun Xu MD, MSc, PhD

Assistant professor

Home address:

6332 Casper Ridge, El Paso, TX, 79912

Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 3 Curriculum Vitae

Chun Xu M.D., Ph.D.

Citizenship: Canadian, US Permanent resident Current Position: assistant professor Address: 6332 Casper Ridge, El Paso, TX USA 79912 Email: acrgbk@r.postjobfree.com Highlights of Qualifications

Meticulous, highly motivated professional specialized in human molecular biology and molecular genetics for monogenic and complex disorders.

Education

1994 – 1999 Ph.D. in Neurology at Department of Neurology, Karolinska Institute, Stockholm, Sweden. Doctoral Thesis: Candidate genes and chromosomal loci in multiple sclerosis (April, 1999) 1989 – 1992 Master’s Degree in cancer genetics and biology at Department of GYN/OBS, Harbin Medical University (HMU), China

1984 – 1989 M.D. Department of Medicine, HMU, China Working Experience

I have research experience and technical capability in the areas of study design, cost-effectiveness evaluation, burden of disease and outcomes research. I have strong project management skills and experience with advanced design & basic statistical analysis, systematic reviews and knowledge of administrative. I have working experience in clinical research for a number of human diseases, such as diabetes, multiple sclerosis, neuropsychiatric disorders, and autoimmune diseases. I have completed a number of Institutional Review Board (IRB) protocols and obtained these IRBs successfully for my research projects.

Feb. 1, 2011-present, an assistant professor (Tenure-Track) at Texas Tech University Health Sciences Center Paul L. Foster School of Medicine, Departments of Pediatrics and Psychiatry. My responsibility: research and teaching in clinical genetics, population genetics, human molecular genetics, and pharmacogenetics/pharmacogenomics genetics for human diseases using cutting edge technology (e.g., next generation sequencing). In addition to research, I teach seven lectures for clinical residents, two lectures for medical students and graduate students (for detail, please see my Teaching Statement). Sixteen scientific papers published, three more manuscripts submitted in collaboration with other faculties.

Clinical research: I have also clinical working experience, particularly on recruiting psychiatric patients

(early 2004 - present) using DSM-IV criteria, a best-estimation consensus procedure using the Diagnostic Interview for Genetic Studies (DIGS) and asking eligible patients or families to give written consent and complete questionnaires for a number of research projects, including neuropsychiatric patients. Translational research: supervised clinicians (including psychiatrists and oncologists on their pharmacogenetics research projects) and researchers on their study design, statistical analysis, interpreted results and writing manuscripts.

I have completed a number of Institutional Review Board (IRB) protocols and obtained seven IRBs successfully for my research projects.

2008- 2010 A research scientist (Non Tenure-Track) at Princess Margaret Hospital/ University Health Network.

Actively involved in research and teaching in clinical genetics, population genetics, pharmacogenetics/pharmacogenomics, and human genetics for human diseases. Supervising a number of junior faculties, residents, graduate students, research associates on their research projects Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 4 Translational research: supervised clinicians and researchers on their study design, statistical analysis, interpreted results and writing manuscripts

2002 – 2008 A postdoctoral fellow (PDF) and research scientist at CAMH, Toronto, Canada Translational research: supervised clinicians and researchers on their study design, statistical analysis, interpreted results and writing manuscripts

2000 – 2002 A PDF at Department of Pharmacology, University of Toronto, Canada 1999 – 2000 A PDF at Toronto Western Hospital, Toronto, Canada 1996-1999 Ph.D. Student Representative at Department of Neurology, Karolinska Institute, Stockholm, Sweden

1992 – 1994 A visiting research scientist, Karolinska Institute, Stockholm, Sweden 1990 – 1992 A Gynecologist, Obstetrician and lecturer, Harbin Medical University (HMU), China Clinic and teaching: my responsibilities include providing prenatal, intrapartal, and postpartum careto high risk and routine obstetrical patients. Perform physical assessment for obstetrical and gynecologic patients, family planning needs, and acute minor gyn. problems. Provide individual counseling, referrals, and education for women. Write and coordinate patient care protocols for midwifery care within the practice setting.

Genetic counseling: my responsibilities include helped people with a family history of genetic disorders to have healthy babies; counsel patients who are at risk of inheriting a genetic disease, about their options. Awards and Distinctions (past five years)

2013 Research award at Critical Research Initiatives of Latino Mental Health Conference in Tampa, FL

2007-2009 NARSAD Young Investigator Awards (US$60,000, July 2007 and June 2009) 2006 Oral presentation award at the 2006 meeting of the Society of Biological Psychiatry, Toronto

2005 Poster presentation award at the 2005 meeting of Biological Psychiatry, Atlanta, USA 2004 Excellence in Research Award, CAMH, Toronto, Canada 1999 PhD travel award Stockholm, Sweden

Research Support

Ongoing Research Support

1. TTUHSC Seed Grant: Whole exome sequencing of neurodevelopmental disorders: a step toward personalized medicine, $25,000, 2014-2015, Role: PI 2. Population Based Mapping of Schizophrenia Genes (RO1MH061884), as co-investigator 3. Genetics Basis of Familial Schizophrenia in Latino Populations (NIH Parent RO1) as co- investigator,

4. A grant of TTUHSC 2014-2016, ADHD risk factors in the Latino population, Role: PI 5. A grant of TTUHSC 2013-2015, Gene discover for neurodevelopmental disorders using whole exome sequencing- steps toward to personalized medicine, Role: PI I 6. TTUHSC Seed Grant: Gene discovery for genetically determined pediatric-onset epilepsies from a predominately Latino population $25,000, 2015-2016, Role: PI I Pending Research Support

1. NIH-R15 grant-submitted: Pathway study and RNA-Seq to identify schizophrenia and bipolar disorder genes. Amount: $100,000/year and for 3 years. Role: PI 2. NIH-RO3 grant-re-submitted on 2014: Pathway-Based Study of Calcium Signaling Genes and the Risk of Bipolar Disorder. Amount: $50,000/year and for 2 years. Role: PI Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 5 3. NIH-R03: submitted October, 2014: Gene Discovery and Infantile Epilepsy in the Latino population. Role: PI

4. NIH-R15 grant-submitted Feb 2015: Pharmacogenimic education and translational research on antidepressant medication in the Latino population. Amount: $100,000/year and for 3 years. Role: PI

5. NIH-RO3 grant-submitted on June 15, 2015: Attention-Deficit/Hyperactivity Disorder recruitment and Whole Exome Sequencing Analysis. Amount: $100,000- 2 years. Role: PI 6. NIH-RO3 grant-submitted on June 15, 2015: Genome wide DNA methylation analysis in two brain regions for schizophrenia and bipolar disorder. Amount: $100,000- 2 years. Role: PI Previous Research Support

1. NARSAD Young Investigator Award (US$60,000, July 2007 and June 2009) 2. Genetic Variation in Transient Receptor Potential Protein Melastatin type 2 and Vulnerability to Bipolar Disorder, $160,000 (2005-2008)

3. Applied Biosystems Real-Time PCR Awards Program for wining an Applied Biosystems 7300 Real- Time PCR System

Service for Scientific Journals

As an editorial board member for Journal of Addiction Medicine & Therapy As an editorial board member for JSM Alzheimer's Disease and Related Dementia As an External Reviewer for

1. Oncotarget 2015: 005413

2. Rheumatology International 2014, RHEI-D-14-00576 3. American Journal of Pathology 2013: MS Number AJP 13-0805 4. Rheumatology International 2013, RHEI-D-13-00868 5. Psychiatry Research 2013, Manuscript ID: PSY-D-13-00048R 6. PLOS ONE 2013, Manuscript ID: PONE-D-13-06180

7. Psychiatry Research 2013, Manuscript ID: PSY-D-13-00048 8. Journal of Psychiatric Research 2012 Manuscript ID:JRP3579R1 9. Psychiatry Research 2012: Manuscript ID: PSY-D12-00122R1 10. Journal of Psychiatric Research 2012 Manuscript ID:JRP3579 11. Psychiatry Research 2012: Manuscript ID: PSY-D12-00122 12. Biological Psychiatry 2011: Manuscript ID: BPS-D11-00829 13. Psychiatry Research 2011: Manuscript ID: PSY-D-11-00171 14. Journal of Psychiatric Research 2011: Manuscript ID: JPR2755 15. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics 2008, Manuscript ID: NPG-07-0395 16. Psychiatry Research 2007: Manuscript Number, PSY-D-07-00357 17. Biological Psychiatry: August 2005; October 2006 18. Bipolar Disorders: May 2004; Feb 2005; May 2007 19. Molecular Psychiatry: Mar 2006

Service on Internal committees:

2012-Present Texas Tech University Health Sciences Center El Paso, TX Member of Admission Committee (3 years term)

2011-Present Texas Tech University Health Sciences Center El Paso, TX Interviewer for Admission Committee for the Medical School 2010-Present Texas Tech University Health Sciences Center El Paso, TX Member, Faculty Searching Committee for the Center of Excellence in Neuroscience 2010-2011 Texas Tech University Health Sciences Center El Paso, TX Organizer of the Distinguished Guest Seminar Series in Biomedical Sciences Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 6 2010-Present Texas Tech University Health Sciences Center El Paso, TX Interviewer for new faculty candidates for Department of Biomedical Sciences 2011 -present Texas Tech University Health Sciences Center El Paso, TX Interviewer for faculty candidate - Dean of the Graduate School for Biomedical Sciences at TTUHSC Selected Publications (Total: 45 Publications, * as corresponding authors) Partial List of Published Work as following

http://www.ncbi.nlm.nih.gov/myncbi/1bUj6yJlXIIAQ/bibliography/40207900/public/?sort=date&direc tion=ascending

1. YongSheng Li, Cynthia Camarillo, Juan Xu, Tania Bedard Arana, Yun Xiao, Zheng Zhao, Hong Chen, ChunXiang Mao, Michael A Escamilla, Alfonso Ontiveros, Humberto Nicolini, Alvaro Jerez, Xia Li, Xu C* Genome-wide methylome analyses reveal novel epigenetic regulation patterns in schizophrenia and bipolar disorder – a pilot study, Biomed Research International 2015;2015:201587*As a corresponding author, 2. Zhao Z, Li Y, Chen H, Lu J, Thompson PM, Chen J, Wang Z, Xu J, Xu C, Li X. PD_NGSAtlas: a reference database combining next-generation sequencing epigenomic and transcriptomic data for psychiatric disorders. BMC Med Genomics. 2014 Dec 31;7(1):512. [Epub ahead of print] 3. Wang KS, Tonarelli S, Luo X, Wang L, Su B, Zuo L, Mao CX, Rubin L, Briones D, Xu C* Polymorphisms within ASTN2 gene are associated age at onset of Alzheimer disease, J Neural Transm. 2015 May;122(5):701-8 4. Kesheng Wang, Daniel Owusu, Yue Pan, Xu C (Review Article), Common Genetic Variants in the HNF1B Gene Contribute to Diabetes and Multiple Cancers, Austin Biomarkers $ Diagnosis 2014, 1(1) 5 5. Kesheng Wang, Xuefeng Liu, Liang Wang, David F. Briones and Xu C, Genetic Variants in the SORL1 Gene are Associated with Age at onset of Alzheimer Disease: A Survival Analysis in press in International Journal of Medical Genetics 2014

6. Xiao Y, Camarillo C, Ping Y, Arana TB, Zhao H, Thompson PM, Xu C, Su BB, Fan H, Ordonez J, Wang L, Mao C, Zhang Y, Cruz D, Escamilla MA, Li X, Xu C*. The DNA methylome and transcriptome of different brain regions in schizophrenia and bipolar disorder. PLoS One. 2014 Apr 28;9(4):e9587. 7. Jia Meng, Yan Li, Cynthia Camarillo, Yue Yao, Yina Zhang, Xu C: The anti-tumor histone deacetylase inhibitor SAHA and the natural flavonoid curcumin exhibit synergistic neuroprotection against amyloid-beta toxicity PLOS ONE, 2014, 9:e85570

8. YongSheng Li, Cynthia Camarillo, Juan Xu, Tania Bedard Arana, Yun Xiao, Zheng Zhao, Hong Chen, ChunXiang Mao, Michael A Escamilla, Alfonso Ontiveros, Humberto Nicolini, Alvaro Jerez, Xia Li, Xu C* Genome-wide methylome analyses reveal novel epigenetic regulation patterns in schizophrenia and bipolar disorder – a pilot study (submitted to Nature Neuroscience, 2013), *As a corresponding author, 9. Ke-Sheng Wang, Nuo Xu, Liang Wang, Lorenzo Aragon, Radu Ciubuc, Tania Bedard Arana, ChunXiang Mao, Leonora Petty, David Briones, Brenda Bin Su, Xingguang Luo, Cynthia Camarillo, Michael A Escamilla, Xu C*, NRG3 gene is associated with the risk and age at onset of Alzheimer disease Journal of Neural Transmission 2014 Feb;121(2):183-92, *As a corresponding author, 10. Ke-Sheng Wang, Nagesh Aragam, Tania Bedard Arana, Thompson, Nicholas, Henry Weisman, Yolanda Posada, ChunXiang Mao, Brenda Bin Su, Cynthia Camarillo, Yu Mao, Michael A Escamilla, Xu C*, Genetic association analysis of ITGB3 polymorphisms with age at onset of schizophrenia Journal of Molecular Neuroscience, 2013, 54:446*As a corresponding author 11. Gonzalez SD, Xu C, Ramirez ME, Zavala JM, Armas R, Contreras SA, Contreras J, Dassori A, Leach RJ, Flores D, Jerez A, Ravento H, Ontiveros A, Nicolini H and Escamilla M, Family-based association of an ANK3 haplotype with bipolar disorder in Latino populations 2013 Translational Psychiatry (2013) 3, e265 12. Xu C*, Warsh JJ, Wang KS, Mao CX, Kennedy JL. Evidence for an interactive effect of the two calcium modulating genes, TRPM2 and iPLA2b on the Risk for Bipolar Disorder, Psychiatric Genetics, 2013 Apr;23(2):86-89, *As a corresponding author

13. Xu C*, JE Mullersman, LWang, BB Su, CX Mao, Y Posada, C Camarillo, Y Mao, MA Escamilla, KS Wang, 2013. Polymorphisms in seizure 6-like gene are associated with bipolar disorder I: evidence of gene gender interaction Journal of Affective Disorders, 145: 95–99, *As a corresponding author, 14. S. Gonzalez, C. Xu, M. Ramirez, J. Zavala, R. Armas, S.A. Contreras, J. Contreras-Rojas, A. Dassori,, R.J. Leach, D. Flores, A. Jerez, H. Raventós, A. Ontiveros, H. Nicolini, M. Escamilla 2012 Evidence for Association Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 7 between L-Type Voltage-Gated Calcium Channel (CACNA1C) Gene Haplotypes and Bipolar Disorder in Latinos: a Family-Based Association Study Bipolar disorders, 2013, Mar;15(2):206-214 15. Xu C*, Nagesh Aragam, Xia Li, Erika Cynthia Villla, Liang Wang, David Briones, Leonora Petty, Yolanda Posada, Tania Bedard Arana1, Grace Cruz, ChunXiang Mao, Cynthia Camarillo, Michael A Escamilla1, Ke- Sheng Wang. BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies Study (2013) PLOS ONE, 8(1), e51674. *As a corresponding author 16. Liu X, Invernizzi P, Lu Y, Kosoy R, Lu Y, Bianchi I, Podda M, Xu C et al, Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet. 2010 Aug;42:658-60. 17. Hirschfield GM, Liu X, Han Y, Gorlov IP, Lu Y, Xu C et al, Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat Genet. 2010 Aug;42:655-7. 18. Hirschfield GM Liu, Xu C, Lu Y, Xie G, Lu Y, Gu X, Walker EJ, Jing K, Juran BD BSc, Mason AL, Myers RP, Peltekian KM, Ghent CN, Coltescu C, Atkinson EJ, Heathcote EJ, Lazaridis KN, Amos CI, Siminovitch KA (2009). Genomewide association analysis identifies HLA, IL12A and IL12RB2 as risk loci for primary biliary cirrhosis. New England Journal of Medicine 360 (24):2544-55 (* I should be 1st author based on my contribution, however, authorship dispute occurred) 19. Li C, Li X, Miao Y, Wang Q, Jiang W, Xu C et al., (2009) SubpathwayMiner: a software package for flexible identification of pathways. Nucleic Acids Research 37 (19) e131 20. Walker EJ, Hirschfield GM, Xu C, Lu Y, Liu X, Lu Y, Coltescu C, Wang K, Newman WG, Bykerk V, Keystone EC, Mosher D, Amos CI, Heathcote EJ, Siminovitch KA (2009) CTLA4/ICOS gene variants and haplotypes are associated with rheumatoid arthritis and primary biliary cirrhosis in the Canadian population. Arthritis Rheum. 2009 Apr;60(4):931-7

21. Xu C, Li PP, Cooke RG, Parikh SV, Wang K, Kennedy JL, Warsh JJ (2009) TRPM2 variants and bipolar disorder risk: confirmation in a family-based association study. Bipolar Disorder. 2009 Feb;11(1):1-10. 22. Xu C, Li P.P., Kennedy JL et al (2008) Further support for association of the mitochondrial complex I subunit gene NDUFV2 with bipolar disorder Bipolar Disorders 10:105 23. Xu C, Li P.P., Cooke R et al (2006) Genetic Evaluation of TRPM2 Variants and BD Risk: Confirmation in a Family-Based Association Study (Am J Psychiatry, submitted). 24. Xu C, Macciardi F, Li P.P et al (2006) Association of the Putative Susceptibility Gene, Transient Receptor Potential Protein Melastatin Type 2, with Bipolar Disorder. Am J Med. Genet. 2006;141B:36-43. 25. Xu C., Warsh J.J., Li PP et al (2005). Further Support for Association of the Mitochondrial Complex I Subunit Gene NDUFV2 with Bipolar Disorder. Biol Psychiatry, 57: 178S. 26. Xu C., Warsh, J. J., Kennedy et al (2004). Association of the Putative Bipolar Disorder Susceptibility Gene, TRPM2, With Bipolar II Disorder. Int. Neuropsychopharm 7: S357. 27. Xu C, Ozbay F, Wigg K et al (2003) Evaluation of adrenergic receptors 2A and Gilles and 1C de la Tourette Syndrome. Am J Med Genet. May 15;119B(1):54-9 28. Xu C, Goodz S, Sellers EM et al (2002) CYP2A6 Genetic Variation and Potential Consequences. Advanced Drug Delivery Review 54, 1245-1256.

29. Xu C, Rao YS, Xu B et al (2002) A novel polymorphism in exon 9 of CYP2A6 gene alters activity in vivo. BBRC 290: 318-324

30. Dai Y, Xu C, Holmberg M et al (2001) Linkage analysis suggests a region of importance for multiple sclerosis in 3p14-13. Genes Immun. Dec;2(8):451-4

31. Barr CL, Xu C, Kroft J, Feng Y et al (2001) Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder. Biol Psychiatry 49: 333-339 32. Xu C, Schachar R, Tannock R et al (2001) Linkage study of the a2A adrenergic receptor in attention-deficit hyperactivity disorder families. American journal of Medical Genetics (Neuropsychiatric Genetics) 105: 159- 162

33. Xu C, Dai YM, Lorentzen JC et al (2001) Linkage analysis in multiple sclerosis of chromosomal regions syntenic to experimental autoimmune disease loci. Europe of Journal of Human Genetics 9: 458-463 34. Xu C, Dai YM and Jan Hillert (1999) Association and linkage analysis of candidate chromosomal regions in multiple sclerosis: indication of disease genes in 12q23 and 7 ptr-15. Europe of Journal of Human Genetics 7(2): 110-116

35. Ligers A, Xu C, Saarinen S, Oleup O, and Hillert J (1999) The CTLA-4 gene is associated with multiple sclerosis. Journal of Neuroimmunology 97: 182-190

36. He Bin, Xu C, Yang B et al (1998) Linkage and association analysis of genes encoding cytokines and myelin proteins in multiple sclerosis. Journal of Neuroimmunology 86:13-19 Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 8 37. Xu C and Jan Hillert (1998) Absence of linkage with the neuronal nitric oxide (NOS1) gene in forty-one multiplex Swedish MS families. European of Journal Neurology 5: 393-396 38. Anna Wedell, Xu C, et al., (1994) A steroid 21-hydroxylase allele concomitantly carrying four disease-causing mutations is not uncommon in the Swedish population. Human Genetics 93: 204-206. 39. Xu C et al., (1991) Studies on chromosomal fragile sites of the patients with GTT, cervical cancer and ovary. Chinese Journal of Gynecology and Obstetrics 25: 157 Invited Presentations (Past Five Years):

1. Invited lecture on “Molecu.ar Genetics and Pharmacogenomics for Neuropsychiatric disorders” at ETSU, March 17, 2014

2. Invited talk of “Novel epigenetic regulation patterns in schizophrenia and bipolar disorder identified in the Latinos by global DNA methylation analysis” in the Critical Research Initiatives of Latino Mental Health Conference in Tampa, Florida on 13-15 June 2013 3. Invited lecture on “Pharmacogenetics in Neuropsychiatric Disorders” at the Department of Biology, Indiana State University, April, 2013

4. Invited speaker on “Moving Toward Personalized Medicine in Psychiatric Disorders” at TTUHSC, El Paso, TX 5. Invited lecture on “Genetics and Pharmacogenetics in Human in Complex Disorders” at the Department of Internal Medicine, TTUHSC, Lubbock, Feb 28, 2013 http://www.ttuhsc.edu/som/cme/grand_rounds/gr_detail.aspx?id=2743 6. “Genetics and Pharmacogenetics in Human Complex Disorders (Examples of Schizophrenia and Bipolar Disorder)” at the Department of Bioinformatics, University of Texas at El Paso, Bell Hall 130A, Friday, 10:30 am, September 12, 2012

http://www.bioinformatics.utep.edu/colloquium/12/09/Xu120914.pdf 7. “Human molecular genetics and nutrigenetics/nutrigenomics” at the Canadian Academy of Natural Health in Toronto, Oct 8 and 9 2011

8. “Molecular Genetics and Pharmacogenetics of Human Complex Diseases” at Texas Tech University, Aug 9, 2010

9. “Genome Wide Association and Next Generation DNA Sequence for Bipolar Disorder and Primary Biliary Cirrhosis” at University Iowa, July 10, 2010 10. “Gene Discovery for Human Complex Diseases” at University Nevada, USA, June 9, 2010 11. “Nutrigenomics Practice and Future” at Harbin Normal University, Harbin, China, Nov 21, 2009 12. “Dissecting the Molecular and Genetic Basis of Human Complex Diseases or Traits” at Harbin Medical University, Harbin, China, Nov 13, 2009

13. “Pharmacogenetics Present and Future” at Harbin Medical University, Harbin, China, Nov 11, 2009 14. “Dissecting the Molecular and Genetic Basis of Human Complex Diseases or Traits” at Memorial University of Newfoundland, St John’s, Canada Oct, 2009 15. “Candidate Gene Strategies for Identifying Disease Susceptibility in Humans”, Cancer Genetic Branch, National Cancer Institute, Rockville, MD, USA, January 15-16, 2008 16. “Molecular Genetics of Psychiatric Disorders and Application of Molecular Genetics in Monogenetic and Complex Diseases in Atlantic Canadians”, Dalhousie University, Halifax, Canada, Oct 22, 2007 17. “Application of nutrigenetics and nutrigenomics in human complex diseases” University of Guelph, Guelph, Ontario, Canada, June 1, 2007

18. “Application of high-throughput SNP genotyping assay in gene mapping and variant identification in human complex diseases” Harbin Medical University, China, June 2006. 19. “Molecular Genetic Studies of Bipolar Disorder, ADHD, and Gilles de la Tourette Syndrome: Candidate Gene Approach” Dalhousie University, Halifax, Canada, August 22, 2006. 20. “Transient Receptor Potential Protein Melastatin type 2 (TRPM2), A Pathophysiological Risk Gene for Bipolar Disorder” Mood Anxiety Round, CAMH, Toronto, Mar 18, 2005. Initial publication and presentation in national & international meetings (2012-2013): 1) Xu C* et al “Whole exome sequencing for epilepsy in the Latino/Hispanic population” as late breaking poster in American Epilepsy 68th Annual meeting at Seattle, December 2014 Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 9 2) Xu C* et al., “Genome-wide methylome and transcriptome analyses reveal novel epigenetic regulation patterns in schizophrenia and bipolar disorder. American Society of Human Genetics Meeting at Boston, Oct 22-26 2013

3) Cynthia Camarillo, Tania Arana, David Briones, Lorenzo Aragon, Radu Ciubuc, Chun Xu*: Genetic Variation and Risk of Age at Onset in Alzheimer’s Disease Using Family-Based Analysis

(*corresponding author) This won 2nd place in the Biomedical Sciences category at 7th Annual TTUHSC Research Colloquium, March 2013

4) Javier Ordonez, Yolanda Posada, Cynthia Camarillo, Brenda Castillo1, Chun Xu: Genomic DNA obtained from saliva and buccal swabs is suitable for genetic variant detection at 7th Annual TTUHSC Research Colloquium, March 2013

5) Yolanda L Posada, Richard Brower, Elizabeth Ledger, Chun Xu*:Associations of stroke and serious psychological distress with epilepsy at 7th Annual TTUHSC Research Colloquium, March 2013 6) Yolanda L Posada, Camarillo, Cynthia; Ordonez, Javier; Camarillo, Aaron; Zavala, Juan M; Michael Escamilla; Xu, Chun*: Calcium Signaling Genes and the Risk of Bipolar Disorder at 7th Annual TTUHSC Research Colloquium, March 2013

7) Xu C*, Aragam N, Li X, Villla EC, Wang L, Posada Y, Arana TB, Cruz G, Mao CX, Camarillo C, Escamilla MA, Wang KS., BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies. 6th Annual Research Colloquium. Texas tech University Health Sciences Center, March 2012 (*corresponding author) 8) Xu C*, Mullersman JE, Wang L, Su BB, Mao CX, Posada Y, Camarillo C, Mao Y, Escamilla MA, Wang KS., Polymorphisms in seizure 6-like gene are associated with bipolar disorder I: evidence of gene gender interaction in International Behavioral Neuroscience Society, Hawaii, USA, June 5-10 2012

9) Xu C*., Aragam N, Li X, Villla EC, Wang L, Posada Y, Arana TB, Cruz G, Mao CX, Camarillo C, Escamilla MA, Wang KS: A meta-analysis of two genome-wide association studies identifies genes/loci associated with negative symptoms in schizophrenia in International Behavioral Neuroscience Society, Hawaii, USA, June 5-10 2012

10) Xu C*, Aragam N, Li X, Villla EC, Wang L, Posada Y, Arana TB, Cruz G, Mao CX, Camarillo C, Escamilla MA, Wang KS., BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies in the World Congress of Psychiatric Genetics, Oct 14-18, 2012

11) Gonzalez, Xu C, M. Ramirez, J. Zavala, R. Armas, S.A. Contreras, J. Contreras-Rojas, A. Dassori,, R.J. Leach, D. Flores, A. Jerez, H. Raventós, A. Ontiveros, H. Nicolini, M. Escamilla., Characterization of CACNA1C and ANK3 Risk Alleles for Bipolar Disorder in Hispanics in the XXth World Congress of Psychiatric Genetics, Hamburg, Germany, Oct 14-18, 2012 12) Xu C, Blackburn AN, Gonzalez S, Villa EC, Ramirez M, Zavala J, Rodriguez M, Camarillo C, Ordonez J, Armas R, Contreras SA, Leach RJ, Flores D, Jerez A, Ontiveros A, Nicolini H, Lehman D, Escamilla M., Rare copy number variants in schizophrenia and bipolar disorder in a Latino Population in American Society of Human Genetics, Annul Meeting, San Francisco, USA Nov 6-10, 2012

Professional Memberships

2010 -- present Member of American Society of Human Genetics 2006 – present Member of the international Society of Psychiatric Genetics 2003 – present Member of the Society for Neuroscience 2006 – present Member of the Continuing Mental Health Education committee, University of Toronto 2002 – present Member of the Nutritional Immunology 2001 – 2002 Member of the American Society for Pharmacology and Experimental Therapeutics HOBBIES: Travel 2. Sport 3 Dance 4. Nutrition

Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 10 Reference Contact List

1) Dr. Jim Kennedy

Section Head, Neurogenetics, Director Neuroscience Centre for Addiction and Mental Health

250 College Street, Room R20, Toronto, ON, Canada, M5T 1R8 Tel: 416-***-**** ext 4987; Fax: 416-***-****

E-mail: acrgbk@r.postjobfree.com

2) Sharon Miksys Ph.D.

Scientist, CAMH

Dept. Pharmacology

University of Toronto

1 King's College Circle

Ontario, Canada, M5S 1A8

Tel: 416- 978-5155 Fax: 416- 978-6395

E-mail: acrgbk@r.postjobfree.com

3) Ke Sheng Wang Ph.D.

Department of Biostatistics and Epidemiology,

College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN 37614-1700, USA. Tel.: +1-423-***-****;

Fax: +1-423-***-****.

E-mail address: acrgbk@r.postjobfree.com (K.S. Wang)

4) Tania B. Arana, Ph.D.

Assistant Dean for Admissions and Student Affairs

Associate Professor, Biomedical Sciences

Burrell College of Osteopathic Medicine at New Mexico State University Genesis Building C

3655 Research Drive

Las Cruces, NM 88003

P: 575-***-****, Cell: 915-***-****

acrgbk@r.postjobfree.com

5) Brenda Su, PhD

Research scientist

Labatt Heart Center

The Hospital for Sick children

Tel: 416-***-****, E-mail: acrgbk@r.postjobfree.com

Teaching Statement

Chun Xu Ph.D. M.D.

Overview

Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 11 Two primary factors motivated me to pursue an academic career: teaching and research. These two factors go hand in hand, always interacting with each other. As a clinical physician, molecular biologist, and human geneticist, I envision teaching to be an integral part of my career profile because I believe that scientific findings are most valuable when shared with, and transferred to, others. The challenge is in bringing students of diverse backgrounds and interests together to the point where they are capable of applying what they have learned from the classes. The rewards are not only in the enjoyable sharing and communicating of knowledge, but also in the new perspectives and inspiration gained from students through teaching. Teaching Experience

During my Postdoctoral training and assistant professor, I actively participated in the following teaching courses, seminars, workshops and international conferences: 2011 Jan-present TTUHSC, El Paso TX

Lectures for clinicians, residents, medical students and graduate students on 1. Personalized medicine, Genomic medicine,

2. Advanced Human Molecular Genetics: genome-wide association study for human complex diseases, next- generation sequence technology (such as whole genome sequence, Global DNA methylation sequence, Transcriptome sequence), high-throughput SNP genotyping, microarray genomics, allelic-specific gene expression, DNA chip (e.g., Affymetrix, Illumina), copy number of variation (CNV), siRNA, microRNA technologies, proteomics, bioinformatics

3. Molecular genetics of neurological diseases, cardiovascular diseases, psychiatric disorders and psychological traits, autoimmune diseases, cancer genetics. Genetics of aging 4. Pharmacogenetics/pharmacogenomics, nutrigenetics/nutrigenomics 2002-2010 Central for Addiction & Mental Health, Princess Margaret Hospital/ University Health Network, Toronto, Canada

Lectures, seminars and workshops for clinicians, medical students, graduate students on 1. Fundamentals of Human molecular genetics (including: Mendelian and complex traits, The Human Genome Project, Disease gene localization and identification, Population variation, disease occurrence, genotypes and phenotypes, Mutational mechanisms and consequences of mutation, Current understanding of epigenetic processes, Current strategies and challenges in gene and gene-based therapies) 2. Principles of Genetic Analysis (Laboratory experiments in human genetics, linkage and recombination, complementation, analysis of chromosome rearrangements, mutant selection and analysis in human), 3. Some lectures are the same as 1-4 in 2011-present 2005- 2011 Canadian Academy of Natural healthy, Toronto ON, Canada 1. Nutrigenetics/nutrigenomics

1989-1992 Harbin Medical University, China

Lectures for medical students on clinical skills in Obstetrics and Gynecology, genetic counseling in English The Trainees from My Research Laboratory:

2008-Dec 2010, Princess Margaret Hospital/ University Health Network, Toronto, Canada Postdoctoral fellows: S. Pathan, D. Phil and Erin J. Walker, Research associates: Lu Y, Xie G

2011, Jan –present

U10CP8 for 250 medical students. I am a mentor of research projects for eleven medical students, including Cruz G, Thompson N,

Graduate students for 40 students: GBSE 5221, Advanced Human Genetics (2 lectures); GBSE5225, Immunology (2 lectures);

I am supervisor for four students (e.g., Ordonez J). Research associates: Posada Y

Mentored students (eight medical students, four residents, two graduate students) on the research projects and a number of papers were published.

Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 12 Overall, I have taught a very wide variety of courses to students of diverse backgrounds. Those teaching experiences were instrumental in determining my academic path, by instigating my commitment to teaching as well as research. Through my academic years, my teaching evaluations have been consistently excellent.

Teaching Philosophy

My teaching philosophies include, but are not limited to, dynamic interaction, hands-on experience, assistant techniques, and assessments.

Dynamic interaction: Teaching is a dynamic process. My goal is to fully develop a teaching style that is sufficiently flexible to accommodate the various needs, levels, and inter-individual differences among students. As my teaching is still evolving, it will be very important to keep an open mind to ideas from the current educational literature, practical experience, and feedback from students and colleagues. Another aspect of the dynamic property of teaching is that teaching goes beyond the classroom; it is always important for an instructor to be available and to foster a relationship with students outside of class. In the past, when teaching undergraduate students, I have typically provided some informal problem blitz sessions, particularly before exams. Hands-on experience: Teaching should be more than transmitting information. Another important part of teaching is to inspire students to explore problems in depth and to develop research skills. I would like to give students the chance to practice the knowledge they have learned in the classroom. For instance, in neurogenetic classes, I provided undergraduate students with opportunities to design and work on a specific experiment. After finishing experiments, they collected data, conducted statistical analyses, and reported their findings in a written document. This “learning by doing” approach was very effective, and students found it easier to grasp and gain a deeper understanding of, complicated concepts. Assistant techniques: Using new media such as PowerPoint presentations with animation has proved to be an effective method in my previous teaching, seminar, workshop, and international oral presentations. It helped to make seemingly inconceivable and complex information vivid and understandable. In addition, I also would like to develop web-based online discussion groups to allow students to formulate opinions, and thus extend and deepen in-class discussion.

Assessment practices: Using assessments, such as homework, quizzes, exams, writing assignments, and projects, not only serves to collect information about students’ learning but also to provide them with feedback, and thus to motivate them to correct their mistakes. In most courses, my preference has been to use short writing assignments. I would typically use in-class assigned questions to break up the lecture with periods of discussion. In addition, I prefer a simple mid-course evaluation in which students respond to questions concerning the effectiveness of both my teaching approach and their learning approaches, which helps to determine any adjustments needed to better meet both my own goals and those of the students.

Interests and future plan

Based on my past teaching experience, I am very interested in teaching undergraduate or graduate courses, as listed above. In addition to delivering lectures, I would like to further develop and administer assistant teaching techniques, such as visual and audio media, web-based learning and discussion board, animation, and computer lab. Moreover, I am interested in mentoring and supervising seminars for graduate students, especially in the areas of molecular genetics, pharmacogenetics/pharmacogenomics, nutrigenetics/nutriogenomics of cardiovascular diseases. In summary, I enjoy teaching and supervising, which allows me to advance my own research, while helping students reach their individual educational goals.

Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 13 Statement of Research Interests:

My Previous Research Achievement:

Over the years of postdoctoral training and faculty periods, my research interests have been focus from human molecular genetics biology, advanced human genetics, and pharmacogenetics and nutriogenetis on a number of human complex diseases, such as healthy aging, cardiovascular diseases, cancer, multiple sclerosis, Alzheimer's disease, type 2 diabetes, psychiatric disorders, rheumatoid arthritis, and asthma. I applied traditional linkage analyses, genetic association and most advanced next generation sequencing technology

(whole genome sequence, global methylation sequence, and RNA-seq) and have made following achievements: identified causative mutations for 21-hydroxylase deficiency (Xu C et al., Human Genetics 1994), localized susceptible loci for type 2 diabetes, and identified a number of predisposing loci for multiple sclerosis (Xu et al., 1998, 1999, 2001). I then continued my research as a Postdoctoral fellow and research scientist in Toronto: my achievements included: (1) Confirmation of linkage of the dopamine transporter locus to attention- deficit/hyperactivity disorder (Xu C et al., Biol Psychiatry, 2001); (2) Exclusion mapping of adrenergic receptors alfa2A and a1C in Tourettes Syndrome (Xu et al., Am J Med Genet. 2003); (3) pharmacogenetics in identification and characterization of a novel polymorphism of CYP2A6 gene which alters nicotine activity in vivo in tobacco dependency (Xu et al., BBRC 2002); (4) Demonstration of strong association between TRPM2 variants with BD implicated in pathogenesis of bipolar disorder (BD) using both population-based association and family-based association (Xu et al., 2006, 2009, 2012), (5) Provided further support for the association of the mitochondrial complex I subunit gene NDUFV2 with BD (Xu et al., Biol Psychiatry, 2006, Xu C et al., 2007, 2008, 2009), (6) Genomewide association analysis identifies HLA, IL12A and IL12RB2 as risk loci for primary biliary cirrhosis

(PBC) (Xu C. New England Journal of Medicine, 2009), replication study of PBC (Xu et al., Nature Genetics 2010),

(7) a number of studies on molecular genetics for BD and schizophrenia (SC)(Xu et al., 2011-2014), (8) copy number variation identified in BD and SC in the Latino population, (9) a number of Meta-analysis and endophenotype studies for BD, SC and Alzheimer’s disease (Xu et al., 2010-2014). Current Research:

1) ADHD risk factors and interaction with genes in the Latino population 2) Pharmacogenomics education and translational research on antidepressant treatment response by examining a number of CYP450 genetic variants

3) Understanding pharmacogenetics differences in drug response and tolerability among patients with antidepressant drug treatment by examining a number of CYP450 genetic variants 4) Whole genome sequencing analysis for bipolar disorder, schizophrenia and epilepsy (manuscripts preparation) 5) Whole exome sequencing for epilepsy in the Latino/Hispanic population (presented in AES and will submit manuscript)

6) Biological pathway analysis for BD, SC –focus on calcium signalling pathway (manuscripts preparation) 7) Copy number variation study for cervical cancer (manuscripts preparation) 8) Copy number variants in bipolar disorder and schizophrenia (Xu et al., 2012, presented at American Society of Human Genetics, manuscript preparation),

9) Using next generation sequencing technology: A. global DNA methylation study for bipolar disorder and schizophrenia using peripheral blood (submitted a manuscript to Nature Neuroscience; B. Whole genome DNA methylation for bipolar disorder and schizophrenia (manuscript preparation); C. Transcriptome sequence for BD and schizophrenia (manuscript in preparation).

10) Genome-wide association study in case control design and family study design for Alzheimer disorders (Xu et al., submitted to Am Geriatric Psychiatry)

11) Collaborate with a number of clinicians and basic scientist on biomarker and environmental factor identification for a number of human diseases, including neurological diseases/traits (e.g., Alzheimer’s disease, epilepsy, human longevity), psychiatric disorders (e.g., bipolar disorder, schizophrenia, ADHD, PTSD, OCD, MDD)

Future Research Interests:

Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 14 1. Biomarker and environmental factor identification for human complex diseases A number of human complex diseases, such as cardiovascular disease and diabetes governed by genetic factors have been evidenced using family, twin, and adoption studies. Results of genome-wide linkage scan, genome-wide association (GWA) and candidate gene studies of disease have offered important clues as to chromosomal regions

(e.g., 22q11 deletion associated with syndrome cardiovascular anomalies, PDE4D on 5q21 associated with common polygenic stroke), although to-date no gene(s) or mutation(s) have been identified. Genetic findings for these diseases have led to growing excitement us with the advances in technology of development of GWA, next generation sequencing (NGS) technologies, low-cost, high throughput SNP genotyping. The decoding of the human genome and the research on the human genome will soon uncover the genes for cardiovascular diseases or diabetes. Genotype analysis also has identified genes important in diabetes, cardiac defects, and risk of cardiovascular disease. Many of the genes show a significant correlation between polymorphisms and the incidence of coronary artery disease and heart failure. Recent multi-dimensional approaches of combining genetics, epigenetics, and environment to the study of complex disorders have revealed powerful insights into how genetic marker interacting with environmental factors may underlie their pathogenesis. Accordingly, the objectives of this proposal are: 1) to identify genetic variants and environmental factors, which are responsible for the diseases; 2) to examine specific causative and/or risk genetic variants for the disease phenotypes; 3) to discover other biomarkers, such as epigenetics and transcriptome sequencing profiles in association with diseases using next generation sequencing technologies

Research design and methodology

In collaboration with research scientists and clinicians, 1) we will recruit patients with human complex diseases, 2) collect phenotypes of potential study participants, including diagnostic, epidemiological, and genealogical data, such as family structure, age, sex, socioeconomic status, lifestyle, clinical status, treatment, and prognosis. Parameters of lifestyle and risk factors (BMI, smoking status, alcohol consumption, social network) will follow similar research strategy as previous studies (Williams etal., 2010 and Rizzuto et al., 2012), 3) we will conduct either candidate gene study or genome wide association or next generation sequencing; 4) conduct global DNA methylation sequencing, 5) we will perform statistical and bioinformatics analyses based on phenotypes, DNA methylation profile, and genotypes.

My current ongoing studies are attempting to use emergent strategies to assess the magnitude of genetic, epigenetic and environment between cases (e.g., cardiovascular diseases, psychiatric disorders, and neurological diseases) and controls using GWA, next generation sequencing (NGS) and bioinformatics tools. This research proposal will serve as an important early step in the PI’s long-term goal of translating molecular genetics/genomics knowledge into the prediction, prevention, and creation of novel treatments for the diseases. This project is important and innovative because the approaches of integrating genetics, epigenetics (such as DNA methylation profile), and environmental factors (such as lifestyle) will be combined to comprehensively investigate mechanisms responsible for the diseases. Future expect: Increasing evidence suggest an important role for clinical characteristics, biomarkers, genomic markers, and gene-environment interactions in developing a personalized approach to the prediction of risk for a number of human complex diseases, such as cardiovascular disease (Bassuk, 2014) and AD (Armstrong 2013). We expect that future identified biomarker(s) and interaction of gene-environment represent mechanism to explain the increase susceptibly of these complex diseases. Future generate preliminary data will show feasibility for an NIH-RO1 or R21 application with which we will recruiter more patients and genotype candidate genes for gene-environmental interaction analyses. 2. Effects of Alzheimer’s disease associated genetic markers and DNA methylation profile response to n-3 Polyunsaturated Fatty Acid Supplementation The increasing global prevalence of Alzheimer’s disease (AD) is a major public health concern. Increasing evidence links the shared contribution of genetic and environmental factors (including nutrition, diet) to AD risk. With recent advances in technology, high throughput Genome-wide association studies orand next generation sequencing have improved our understanding of not only the genetic basis of AD, but also the mechanism by which nutrition –and genes interaction since it is clearly that genetic factors only partly explain for an individuals’ predisposition to AD. This research proposal, objectives are to understand current genetic findings and nutrition-gene Dr. Chun Xu’s Application for a MSL or Research Scientist 2015 15 interactions, focusing on the roles of SNPs and CNV in determining individual response to nutrition for AD. Understanding individual macronutrients, dietary patterns and interaction with genes is becoming increasingly important in terms of developing public health strategies and preventing AD or other dementia related disorders. Nutrigenetics offers the potential to improve diet-related disease prevention and therapy, particular for people who carry risk alleles for AD. Specific Objectives: To test whether age, sex, body mass index (BMI), and 50 AD-associated genetic markers (including apolipoprotein E (APOE)) and DNA methylation profiles with the metabolic response to an n-3 polyunsaturated fatty acid (PUFA) supplementation. Methods: In collaboration with faculties at TTUHSC, national and international research institutes, we have and will continue to collect 200 subjects followed a 2-week run-in period based on US’s Food Guide and undergo a 6-week 5 g/day fish oil supplementation (1.9 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Genotyping on these 50 markers, DNA methylation profiles and cardiovascular disease risk factors (for example, triglyceride levels, fasting glucose, plasma total cholesterol) will be measured.

We expect that age, sex, BMI, and certain AD association genotypes (for example, the APOE genotype) contribute to the inter-individual variability observed in the metabolic response to an n-3 PUFA supplementation. Future advances in understanding the complex interaction between genes, nutrition or other non-genetic factors (e.g., epigenetic modification, excise) will help to recede cost for both individual and society and enhance quality of life.

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