Ke Hao Department of Genetics and Genomic Sciences

Ke Hao Department of Genetics and Genomic Sciences Institute of Genomics and Multiscale Biology Mount Sinai School of Medicine One Gustave L. Levy Place – Box 1498 New York, NY 10029-6574 Tel: (212) 659-8534; Fax: (646) 537-8660 Email: [email protected]

Education Doctor of Science 1998-2003 Program for Population Genetics Harvard University, Massachusetts, USA

Bachelor of Science 1993-1997 Department of Biological Sciences and Biotechnology Tsinghua University, Beijing, China

Research Experience

2012 – present Associate Professor Department of Genetics and Genomic Sciences Mount Sinai School of Medicine Research Projects: 1. Cancer genomic and causal network of hepatocellular carcinoma and cholangiocarcinoma 2. Genetic study of RNA editing in brain, depression and suicide 3. COPD among subjects with lung cancer

2007 - 2012 Research Fellow, Rosetta Impharmatics / Merck Research Labs Projects: 1. Systematic characterization of genetic architecture of gene expression (eQTLs) in human tissues (Lung, Liver, Adipose, Blood, Brain, etc.) 2. Cancer genomics  Integrated approaches in hepatocellular carcinoma: clinicopathogical parameters, normal-tumor pairs, expression/SNP arrays, CNV, whole- genome DNA-sequencing and transcriptome-sequencing  Gene-expression and exome-sequencing in breast and ovarian cancer 3. Pharmacogenomics  Identification of biomarkers and construction of classifiers in predicting liver cancer prognostics  Pharmacogenetics study on efficacy of leukotriene inhibitors  Genetic basis of drug induced liver injury (severe adverse event) using exome-sequencing approach 4. Association study on complex human disease using exome-sequencing approach  Hyperlipidemia 5. Meta-genome sequencing study on inflammatory bowel disease  Disease status and treatment efficacy of biologics  Meta-genome sequencing in stool sample and exome-seq on human host 6. Dissecting complex human diseases using GWAS and systems biology approach (Asthma, Diabetes, Osteoporosis, CHD, Schizophrenia, etc.) 7. Pharmacogenetics studies on HSD inhibitor development programs 2005 - 2007 Scientist, Affymetrix, Inc. Projects: 1. Design of microarray for high throughput genotyping and genome wide association study (Affymetrix SNP 500K, 5.0 and 6.0) 2. Algorithm in GWAS, arrayCGH and LOH studies

2003-2005 Postdoctoral Research Fellow; Advisor: Wing H. Wong, PhD Department of Biostatistics, Harvard University Projects: 1. Linkage mapping for human diseases 2. Transcriptional microarray in characterizing survival and recurrence of ovarian cancer 3. Methods development and analyses of microarray data 4. Haplotype and LD analyses of human genome

1998-2003 Graduate Student Program for Population Genetics, Harvard University Projects: 1. Positional candidate gene approaches in asthma 2. Candidate gene study of preterm delivery 3. Pharmacogenetics study of anti-hypertensive therapy

Selected Publications

1. Hao K, Wang X, Niu T, Xu X, Li A, Chang W, Wang L, Li G, Laird N, Xu X. A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods. Hum Mol Genet. 2004 Apr 1;13(7):683-91. 2. Hao K, Peng S, Xing H, Yu Y, Huang A, Hong X, Wang Y, Chen C, Wang B, Zhang X, Liu J, Zhu G,

Huo Y, Chen D, Zhao X, Ronnenberg A, Wu D, Niu T, Xu X. 3 Adrenergic receptor polymorphism and obesity-related phenotypes in hypertensive patients. Obes Res. 2004 Jan;12(1):125-30. 3. Hao K, Xu X, Laird N, Wang X, Xu X. Power estimation of multiple SNP association test of case-control study and application. Genet Epidemiol. 2004 Jan; 26(1):22-30. 4. Hao K, Niu T, Sangokoya C, Li J, Xu X. SNPkit: an efficient approach to systematic evaluation of candidate single nucleotide polymorphisms in public databases. Biotechniques. 2002 Oct; 33(4):822-8. 5. Li D, Xing H, Hao K, Peng S, Wu D, Guang W, Huang A, Wang Y, Zhang Y, Yu Y, Li J, Chen C, Wang B, Zhu G, Huo Y, Chen D, Ronnenberg A, Niu T, Xu X; Hypertensive patients from two rural Chinese counties respond differently to benezapril: Anhui hypertension health care study; Annals of Epidemiology, 2004, Feb; 14(2):123-8 6. Hao K, Li C, Rosenow C, Wong W; Estimation of genotype error rate using samples with pedigree information – an application on GeneChip® Mapping 10K array; Genomics. 2004 Oct; 84(4): 623-30 7. Hao K, Li C, Rosenow C, Wong W; Detect and adjust for population stratification in population-based association study using genomic control markers -- an application of Affymetrix Genechip® Human Mapping 10K array; European Journal of Human Genetics, 2004 Dec;12(12):1001-6. 8. Huang G, Xing H, Hao K, Peng S, Wu D, Guang W, Huang A, Wang Y, Zhang Y, Yu Y, Li J, Chen C, Wang B, Zhu G, Huo Y, Chen D, Ronnenberg A, Niu T, Xu X; β2 Adrenergic receptor Arg16Gly polymorphism and therapeutic effect of benazepril on essential hypertension in two Chinese populations, Clinical and Experimental Hypertension, 2004 Aug; 26(6): 581- 92 9. Hao K, Peng S, Huang A, Hong X, Zhang Y, Zhao X, Xing H, Li J, Ronnenberg A, Xu X, Niu T, Xu X;

Electrocardiographic left ventricular hypertrophy, β3 adrenergic receptor polymorphism and endpoint of ACEI treatment of hypertension; Journal of applied research in clinical and experimental therapeutics, 2004, 4(2): 293-301 10. Hao K and Wang X, Incorporating individual error rate into association test of unmatched case-control design; Human Heredity, 2004;58(3-4):154-63. 11. Hao K, Chen C, Wang B, Yang J, Fang Z, Xu X; Familial aggregation of airway responsiveness -- a community-based study; Annals of Epidemiology, 2005 Nov;15(10):737-43. 12. Leykin I, Hao K, Meyer N, Cheng J, Pollak M, Smith R, Wong W, Rosenow C, Li C; dChipLinkage: parametric linkage analysis and visualization of high-density oligonucleotide SNP Array Data. BMC genetics, 2005; Feb 15;6(1):7. 13. Hao K, Niu T, Xu X, Fang Z, Xu X; Single nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness; Human Genetics, 2005 Apr;116(5):378-83. 14. Hao K, Liu S, Niu T; A sparse marker extension tree algorithm for selecting the best set of haplotype tagging single nucleotide polymorphisms, Genet Epidemiol. 2005 Dec; 29(4):336-52 15. Dahia P, Hao K, Rogus J, Colin C, Ross K, Magoffin D, Hayashida C, Aronin N, Cascon A, Armelin A, Toledo S, Li C, Stiles C. Integrated linkage analysis, genome-wide loss of heterozygosity mapping and transcription profiling reveal a novel susceptibility locus for pheochromocytoma; Cancer Res. 2005 Nov 1;65(21):9651-8. 16. Beroukhim R, Lin M, Park Y, Hao K, Zhao X, Garraway LA, Fox EA, Hochberg EP, Mellinghoff IK, Hofer MD, Descazeaud A, Rubin MA, Meyerson M, Wong WH, Sellers WR, Li C. Inferring loss-of- heterozygosity from unpaired tumors using high-density oligonucleotide SNP arrays. PLoS Comput Biol. 2006 May; 2(5):e41 17. Peng S, Yu Y, Hao K, Xing H, Li D, Chen C, Huang A, Hong X, Feng Y, Zhang Y, Li J, Wang B, Wu D, Wang X, Xu X. Heart rate-corrected QT interval duration is significantly associated with blood pressure in Chinese hypertensives. J Electrocardiol. 2006 Apr; 39(2):206-10. 18. Wamunyokoli FW, Bonome T, Lee JY, Feltmate CM, Welch WR, Radonovich M, Pise-Masison C, Brady J, Hao K, Berkowitz RS, Mok S, Birrer MJ. Expression profiling of mucinous tumors of the ovary identifies genes of clinicopathologic importance. Clin Cancer Res. 2006 Feb 1; 12(3 Pt 1):690-700. 19. Bonome T, Lee JY, Park DC, Radonovich M, Pise-Masison C, Brady J, Gardner GJ, Hao K, Wong WH, Barrett JC, Lu KH, Sood AK, Gershenson DM, Mok SC, Birrer MJ; Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary; Cancer Res. 2005 Nov 15; 65(22):10602-12 20. Feltmate CM, Lee KR, Johnson M, Schorge JO, Wong KK, Hao K, Welch WR, Bell DA, Berkowitz RS, Mok SC.; Whole-genome allelotyping identified distinct loss-of-heterozygosity patterns in mucinous ovarian and appendiceal carcinomas. Clin Cancer Res. 2005 Nov 1; 11(21):7651-7. 21. Hao K, Di X, Cawley S, LdCompare: rapid computation of single- and multiple-marker r2 and genetic coverage. Bioinformatics. 2007 Jan 15;23(2):252-4. Epub 2006 Dec 5. 22. Hao K and Cawley S, Differential dropout among SNP genotypes and impacts on association tests. Hum Hered. 2007;63(3-4):219-28. Epub 2007 Mar 7. 23. Birrer MJ, Johnson ME, Hao K, Wong KK, Park DC, Bell A, Welch WR, Berkowitz RS, Mok SC. Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J Clin Oncol. 2007 Jun 1;25(16):2281-7. 24. Hao K, Genome-wide selection of tag SNPs using multiple-marker correlation; Bioinformatics. 2007 Dec 1;23(23):3178-84. Epub 2007 Nov 15. 25. Stany MP, Bonome T, Wamunyokoli F, Zorn K, Ozbun L, Park DC, Hao K, Boyd J, Sood AK, Gershenson DM, Berkowitz RS, Mok SC, Birrer MJ. Classification of ovarian cancer: a genomic analysis. Adv Exp Med Biol. 2008; 622:23-33. 26. Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, Zhu J, Millstein J, Sieberts S, Lamb J, GuhaThakurta D, Derry J, Storey JD, Avila-Campillo I, Kruger MJ, Johnson JM, Rohl CA, van Nas A, Mehrabian M, Drake TA, Lusis AJ, Smith RC, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich R. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008 May 6;6(5):e107. 27. Hao K, Schadt EE, Storey JD, Calibrating the performance of SNP arrays for whole-genome association studies. PLoS Genet. 2008 Jun 27;4(6):e1000109. 28. Hao K, Luk JM, Lee N, Mao M, Zhang C, Ferguson MD, Lamb J, Dai H, Ng IO, Sham PC, Poon R. Predicting Prognostics in Hepatocellular Carcinoma after Curative Surgery with Common Clinicopathologic Parameters. BMC Cancer. 2009 Nov 3;9:389. 29. Hao K, Chudin E, McElwee J, Schadt EE, Accuracy of Genome-Wide Imputation of Untyped Markers and Impacts on Statistical Power for Association Studies. BMC Genetics, 2009, Jun 16;10:27. 30. Mok SC, Bonome T, Vathipadiekal V, Bell A, Johnson ME, Wong KK, Park DC, Hao K, Yip DK, Donninger H, Ozbun L, Samimi G, Brady J, Randonovich M, Pise-Masison CA, Barrett JC, Wong WH, Welch WR, Berkowitz RS, Birrer MJ. A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2. Cancer Cell. 2009 Dec 8;16(6):521-32. 31. Hao K and Kasarskis A, Empirical Data Indicates a Primarily Additive Genetic Model for Expressional QTLs. iCBBE 2010 IEEE CFP1029C-CDR, ISBN: 978-1-4244-4713-8 32. Hao K, Chudin E, Greenawalt D, Schadt EE. Magnitude of stratification in human populations and impacts on genome wide association studies. PLoS One. 2010 Jan 13;5(1):e8695. 33. Yang X, Zhang B, Molony C, Chudin E, Hao K, Zhu J, Gaedigk A, Suver C, Zhong H, Leeder JS, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich RG,Slatter JG, Schadt EE, Kasarskis A, Lum PY. Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. Genome Res. 2010 Aug;20(8):1020-36. Epub 2010 Jun 10. 34. Zhang ZJ, Hao K, Shi R, Zhao G, Jiang GX, Song Y, Xu X, Ma J. GSTM1 and GSTT1 null polymorphisms, smoking and their interaction on oral cancer: a HuGE review and meta-analysis. Am. J. Epidemiology. 2011 Apr 15;173(8):847-57. Epub 2011 Mar 24. 35. Lamb JR, Zhang C, Xie T, Wang K, Zhang B, Hao K, Chudin E, Fraser HB, Millstein J, Ferguson M, Suver C, Ivanovska I, Scott M, Philippar U, Bansal D, Zhang Z, Burchard J, Smith R, Greenawalt D, Cleary M, Derry J, Loboda A, Watters J, Poon RT, Fan ST, Yeung C, Lee NP, Guinney J, Molony C, Emilsson V, Buser-Doepner C, Zhu J, Friend S, Mao M, Shaw PM, Dai H, Luk JM, Schadt EE. Predictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting. PLoS One. 2011;6(7):e20090. Epub 2011 Jul 5. 36. Hao K, Lamb J, Zhang C, Xie T, Wang K, Zhang B, Chudin, Lee N, Mao M, Zhong H, Ferguson M, Ng I, Sham P, Poon P, Molony C, Schadt EE, Dai H and Luk JM. Clinicopathological and Gene Expression Parameters Predicts Liver Cancer Prognosis, BMC Cancer, 2011 Nov 9;11:481. 37. Woo S, Schadt EE and Hao K. Bayesian method to predict individual SNP genotypes from gene expression data. Nat Genet. 2012;44(5):603-8. 38. Kreimer A, Litvin O, Hao K, Molony C, Pe'er D, Pe'er I. Inference of modules associated to eQTLs. Nucleic Acids Res. 2012 Jul 1;40(13):e98. Epub 2012 Mar 24. 39. Hao K, Bossé Y, Nickle DC, Paré PD, Postma DS, Laviolette M, Sandford A, Hackett TL, Daley D, Hogg JC, Elliott WM, Couture C, Lamontagne M, Brandsma C, van den Berge M, Koppelman G, Reicin AS, Nicholson DW, Malkov V, Derry JM, Suver C, Tsou JA, Kulkarni A, Zhang C, Vessey R, Opiteck GJ, Curtis SP, Timens W, Sin DD. Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma, PLoS Genetics, in press

Lecture and Oral Presentations Bioconductor Workshop 2006, Seattle WA Title: rapid computation of single- and multiple-marker r2 and genetic coverage

American Society of Human Genetics 2008 Philadelphia PA Title: accuracy of genome-wide imputation of untyped markers and impacts on statistical power for association studies

The West Lake Conference 2009, Hangzhou, China Title: magnitude of stratification in human populations and impacts on genome wide association studies. International Conference on Bioinformatics and Biomedical Engineering, 2010 Title: empirical data indicates a primarily additive genetic model for eQTLs

Published Software SNPkit, implemented in PERL, designs mutagenic PCR-RFLP assays for SNP evaluation and genotyping. MinP, implemented in C++, conducts multiple SNP association tests and provides global p-values. GERE (Genotyping Error Rate Estimator), implemented in PERL/TK, estimates genotyping error rate in pedigree data. LdCompare, implemented in C++, compute single- and multi- marker r2 at a genome wide scale. MultiTag, implemented in C++, Genome-wide selection of tag SNPs using multiple-marker correlation