BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Xuefeng Bruce Ling Sr. Scientist eRA COMMONS USER NAME bxling EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION (if YEAR(s) FIELD OF STUDY applicable) 1990 Biochemistry Fudan University, China B.S. UCLA, US M.A. 1994 Molecular Biology UCLA, US Ph.D. 1996 Biological Chemistry Stanford University, US Postdoctoral 1996-1998 Computer Science Postdoctoral Stanford University Medical Center, US 1996-1998 Medicine/Oncology Fellow Leavey School of Business, Santa Clara 2000-2001 Business Administration University, US A. Personal statement The proposed research and the implementing multidisplinary team, headed by Dr. Lu Tian, offer an unparrelled opportunity to translate cutting edge technologies and breakthroughs in proteomics, machine learning based biomarker discovery, and modern medicine into a predictive test to overcome the challenges of neonatal disease. Ever since my interdisplinary postgraduate training in computer science and medicine at Stanford University, I have been trying to tap the power of high throughput biotechnologies and computational innovations to advance the therapy and practice of medicine. Through industrial and academic endeavors, I have proved myself as an experienced team leader, algorithm/software developer, and scientist with a record of accomplishments in the innovative use of artificial intelligence and high throughput biotechnologies for drug target identification, drug design and discovery, biomarker discovery/validation, and translational medicine. Five years ago, I was recruited to Stanford’s ground breaking translational medicine program funded by the Children’s Health Initiative, which brought together engineers, scientists, and clinicians to collaborate on biotechnology projects. Sucessful collaborations included various Stanford clinicians resulted in the creation of a plasma and/or urine diagnostic/prognostic panels for varioius challenging diseases including renal allograft dysfunctions, Kawasaki Disease, systemic juvenile idiopathic arthritis (sJIA), glioblastoma, and necrotizing colitis etc. The Tian Lab is part of the Stanford statistics community at Stanford University. Dr. Tian focuses on novel statistical method development and apply machine learning in clinical science. Dr. Sylvester is the head of national neonatal disease network, specializing in necrotizling colitis disease research and management. Therefore, this proposal that combines this cross-functional teams’ expertise in statistical machine learning, the cutting edge proteomics profiling technology, and years’ of clinical experience has been carefully planned and solidly positioned to address neonatal disease challenge: a predictive algorithm for high-risk neonatal disease progression. B. Positions and Honors Positions 2007 Senior Scientist, Translational Medicine Program, School of Medicine, Stanford University 2006 Consultant, Biotechnology Core, Lucile Packard Children’s Hospital, Stanford University 2004 - 2005 Director, Research & Development Informatics Amgen San Francisco. 2002 - 2004 Research Director, Tularik Inc. 2001 - 2002 Director, R&D informatics, Tularik Inc. 2000 - 2001 Associate Director, Research & Development, DoubleTwist, Inc. 1999 - 2000 Project manager, Research, Pangea System, Inc. 21 Principal Investigator/Program Director (Last, First, Middle): Burns, Jane C. 1998 - 1999 Computation/Bioinformatics Scientist, Incyte Pharmaceuticals, Inc. Service 2005 Member, Journal Editorial Board, Cancer Informatics 1997 Member, Medical Advisor Board,National Kidney Foundation of Northern California Honors 1997 – 1998 Walter Berry Medical Research Award 1997 National Kidney Foundation Research Award 1996 Dean's Fellowship, Stanford University 1992 -1993 University Fellowship, UCLA, CA 1991 - 1992 University Fellowship, University of Iowa, IA 1990 - 1991 University Fellowship, Fudan University, China 1990 Summa cum laude, Fudan University, China 1986 – 1990 University Fellowship, Fudan University, China C. 16 selected peer-reviewed publications (from 30 publications) Most relevant to the current diagnostic application development 1) Ling XB, Park JL, Carroll T, Nguyen KD, Lau K, Macaubas C, et al. Plasma profiles in active systemic juvenile idiopathic arthritis: biomarkers and biological implications. Proteomics. In press. 2) Ling XB, Lau K, Deshpande C, Park JL, Milojevic D, et al. Urine peptidomic and targeted plasma protein analyses in the diagnosis and monitoring of systemic juvenile idiopathic arthritis. Clinical proteomics. In press. 3) Ling XB, Mellins ED, Sylvester KG, Cohen, HJ. 2010. Urine peptidomics for clinical biomarker discovery. Advance in Clinical Chemistry. 51: 181-213. 4) Ling XB, Sigdel, TK, Lau K. Lin Y, Lau I, Schilling J, Sarwal M. 2010. Integrative Urinary Peptidomics in Renal Transplantation Identifies Novel Biomarkers for Acute Rejection. JASN 21:646-653. 5) Ling XB, Zhou L, Cai M, Wang Q, Lau K, Zhao JJ, Schilling J, Chen L. 2009. Tumor associated proteome and peptidome analyses for multiclass cancer discrimination. Clinical Proteomics 5:163-169 6) Ling XB, Cohen HJ, Jin J, Lau I, Schilling J. 2009. FDR made easy in differential feature discovery and correlation analysis. Bioinformatics 25:1461-2. 7) Yang Q, Whitin JC, Ling XB, Nayak N, Cohen HJ, Jin J, Schilling J, Yu TT, and Madan A. 2009. Plasma biomarkers in a mouse model of preterm labor. Pediatric Research 66:11-6. 8) Liu JJ, Cutler G, Li W., Pan Z., Peng S, Hoey T, Chen L, Ling XB. 2005. Multiclass cancer classification and biomarker discovery using GA-based algorithms. Bioinformatics 21: 2691-2697. Additional recent publications of importance to the field 1 ).Allibhai T, DiGeronimo R, Whitin J, Salazar J, Yu,TT, Ling XB, Cohen H, Dixon,P, Madan A. 2009. Effects of moderate versus deep hypothermic circulatory arrest and selective cerebral perfusion on cerebrospinal fluid proteomic profiles in a piglet model of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 138(6):1290-6. 2) Sigdel TK, Ling XB, Lau K, Li L, Schilling J, Sarwal M. 2009. Urinary peptidomic analysis identifies potential biomarkers for acute rejection of renal transplantation. Clinical Proteomics 5, 103-113. 3) Ling, XB. 2008. High throughput screening informatics. Comb Chem High Throughput Screen. 11(3):24957. 4) Li WX, Li L, Eksterowicz J, Ling XB, Cardozo M. 2007. Significance Analysis and Multiple Pharmacophore Models for Differentiating P-Glycoprotein Substrates. J. Chem. Inf. Model. 47: 2429-2438. 5) Chen Z, Wang W, Ling XB, Liu JJ, Chen L. 2006. GO-Diff: Mining functional differentiation between ESTbased transcriptomes. BMC Bioinformatics 7: 72. 6) Li S, Cutler G, Liu JJ, Hoey T, Chen L, Schultz PG, Liao J, Ling XB. 2003. A comparative analysis of HGSC and Celera human genome assemblies and gene sets. Bioinformatics 19:1597-1605. 7) Pei L, Peng Y, YangY, Ling XB, van Eyndhoven WG, Nguyen K, Rubin M, Hoey T, Powers S and Li, J 2002. PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer. Cancer Res. 62 (19):5420-4. 22 Principal Investigator/Program Director (Last, First, Middle): Burns, Jane C. 8) Pouliot Y, Gao J, Su Q, Liu G, Ling XB. 2001. DIAN, a Novel Algorithm for Genome Ontological Classification. Genome Res. 11(10):1766-79. Software Copyright 1. “MASS-Conductor” - High throughput proteomic biomarker discovery platform. Ling XB 2. Stanford “FDR server” Ling XB 3.“DIAN” - A novel computational algorithm for genome ontological classification. Ling XB D. Research Support: Ongoing Research Support Lucile Park Foundation (Supervisor: Cohen) 10/1/2010 – 2/1/2011 Children’s health initiative (CHI) transition fund currently supports all of Dr. Ling’s salary and benefits such that 100% of his efforts are focused on the translational medicine efforts in Stanford Lucile Park Children’s Hospital. Pediatric disease biomarker discovery and translational analytic support. Selected Completed Research Support Corporate research project (PI: Ling) 1/00-1/01 DoubleTwist, Inc. Develop high throughput novel algorithms for highthroughput genome ontological classification Corporate research project (PI: Ling) 1/01-1/04 Tularik Inc. Develop high throughput computation platform (the Discovery Platform) to enable globally integrated high throughput small molecule screening in either cell based or biochemical assays. Corporate research project (PI: Ling) 1/01-1/03 Tularik Inc. Developed informatics platform for array CGH to screen for genetic lesions in cancer to discover novel cancer targets Corporate research project (PI: Ling) 1/04-1/05 Amgen San Francisco Develop compound property based CSAR/QSAR models to address compound PGP (P-glycoprotein, Efflux pump) liability in compound brain permeability for CNS programs Corporate research project (PI: Ling) 1/04-1/05 Amgen San Francisco Discover cancer targets through the large-scale tumor tissue sequencing and SNP analysis of somatic mutations in the potential targets of the interest and to explore their implications in cancer Children’s health initiative (CHI) Lucille Packard Foundation (PIs: Krensky, Cohen) 1/06-10/09 Develop proteomic (2D gel DIGE and LCMS) platforms to discover diagnostic and prognostic biomarkers for in urine, plasma and tissue. Develop high throughput computational platform for feature detection and discovery of discriminative features in LCMS based biomarker discovery 23