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INACTIVATION OF SAG/RBX2/ROC2 E3 UBIQUITIN LIGASE SUPPRESSES KRASG12D-DRIVEN LUNG TUMORIGENESIS UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER • BOSTATISTICS UNIT • M2541 • 1420 WASHINGTON HEIGHTS • ANN ARBOR, MI 48109-5473 PHONE (734) 763-6898 • FAX (734) 936-4540 • E-MAIL [email protected] LILI ZHAO EDUCATION September 2003 – December 2006 University of Iowa, Iowa City, IA Ph.D., Statistics Dissertation Title: “Bayesian Sequential Analysis for Phase II Clinical Trials” September 2001 – September 2003 University of Iowa, Iowa City, IA M.S., Statistics July 1995 – July 1999 The Capital University of Economics and Business, Beijing, China B.S., Marketing and Economics PROFESSIONAL EXPERIENCE Research Assistant Professor March 2014 – present Biostatistics Department, University of Michigan, Ann Arbor, Michigan Research Investigator September 2011 – March 2014 Biostatistics Department, University of Michigan, Ann Arbor, Michigan Statistician Lead December 2007 – September 2011 Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan Senior Statistician September 2006 – December 2007 Becton, Dickinson and Company, Baltimore, MD Last Updated: April 30, 2015 Page 1 EXTERNAL PROFESSIONAL SERVICE Manuscript Referee for: Clinical Cancer Research Contemporary Clinical Trials Statistics in Medicine Statistical Modeling Journal of Clinical Oncology Biometrical Journal Biometrics Journal of the American Statistical Association BMC Pediatrics Journal of Applied Statistics Annals of Human Genetics Future Science Statistical Applications in Genetics and Molecular Biology Computer Methods and Programs in Biomedicine Pharmaceutical Statistics PLOS Computational Biology International Statistical Review Book Reviewer: “Bayesian Methods in Epidemiology” by Lyle D. Broemeling, Chapman & Hall/CRC, 2014 Reviewer: NSA-AMS grant, 2014 PRESENTATIONS Contributed Presentation, “Bayesian Sequential Analysis for Survival Data.” August 2006, JSM Annual Conference. Invited Presentation, “Bayesian Hierarchical Changepoint Methods in Modeling the Tumor Growth Profiles in Xenograft Experiments.” October 2009, Bowling Green State University. Invited Presentation, “Bayesian Decision Sequential Analysis with Survival Endpoint in Phase II Clinical Trials.” January 2010, MD Anderson Cancer Center Bayesian Biostatistics Conference. Invited Presentation, “Bayesian two-stage design in Phase II clinical trials with timeto-event endpoint: A simulation-based decision-theoretic approach.” June 2011, Third IWSM Conference, Stanford University. Invited Presentation, “Bayesian two-stage design in Phase II clinical trials with timeto-event endpoint: A simulation-based decision-theoretic approach.” January 2012, MD Anderson Cancer Center Bayesian Biostatistics Conference. Last Updated: April 30, 2015 Page 2 Invited Presentation, “Bayesian Hierarchical Changepoint Methods in Modeling the Tumor Growth Profiles in Xenograft Experiments.” June 2013, University of Chinese Academy of Sciences, School of Mathematical Sciences. Contributed Presentation, “Bayesian two-stage design in Phase II clinical trials with time-to-event endpoint: A simulation-based decision-theoretic approach.” July 2013, IMS-China international Conference. Invited Presentation, “Bayesian two-stage design in Phase II clinical trials with timeto-event endpoint: A simulation-based decision-theoretic approach.” June 2014, Joint Applied Statistics Symposium of International Chinese Statistical Association and Korean International Statistical Society. Contributed Presentation, “Evaluation of treatment efficacy using a Bayesian mixture piecewise linear model of longitudinal biomarkers.” August 2015, JSM Annual Conference PROFESSIONAL MEMBERSHIPS American Statistical Association, April 2006 to present International Society for Bayesian Analysis, July 2011 to present PEER-REVIEWED PUBLICATIONS Publications (peer-reviewed; published or accepted) 2014-2015 Zhao L, Feng D, Neelon B and Buyse M. Evaluation of treatment efficacy using a Bayesian mixture piecewise linear model of longitudinal biomarkers. Statistics in Medicine, 34(10): 1733-1746, 2015 Zhao L, Shi J, Shearon TH, and Li Y. A Dirichlet process mixture model for survival outcome data: assessing nationwide kidney transplant centers. Statistics in Medicine, 34(8): 1404-1416, 2015 Nadal E, Chen G, Prensner JR, Shiratsuchi H, Sam C, Zhao L, Kalemkerian GP, Brenner D, Lin J, Reddy RM, Chang AC, Capellà G, Cardenal F, Beer DG and Ramnath N. KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma. Journal of Thoracic Oncology, 9(10): 1513-1522, 2014 Jiang Y, Djuric Z, Sen A, Ren J, Kuklev D, Waters I, Zhao L, Uhlson CL, Hong YH, Murphy RC, Normolle DP, Smith WL and Brenner DE. Biomarker for personalizing omega-3 fatty acid dosing. Cancer Prev Res, 7(10):1011-1022, 2014 Arps DP, Jorns JM, Zhao L, Bensenhaver J, Kleer CG and Pang JC. Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast. Annals of Surgical Oncology, 21:4152–4158, 2014 Last Updated: April 30, 2015 Page 3 Brown NA, Rolland DC, McHugh JB, Weigelin HC, Zhao L, Lim MS, ElenitobaJohnson KS, Betz BL. Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res, 20(21): 5517–26, 2014 Kantola S, Virani N, Haus C, Hipp J, Zhao L and Jing X. Prospective Evaluation of Impact of Using The Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience. Journal of the American Society of Cytopathology, 4: 25-29, 2015 Karnak D, Engelke C, Parsels LA, Kausar T. Wei D, Robertson J, Marsh K, Davis M, Zhao L, Maybaum J, Lawrence TS and Morgan MA. Combined inhibition of Wee1 and PARP1/2 for radiosensitization in pancreatic cancer. Clinical Cancer Research, Published OnlineFirst on August 12, 2014 Xie CM, Wei D, Zhao L, Marchetto S, Mei L, Borg JP, and Sun Y. Erbin is a novel substrate of Sag-βTrCP E3 ligase that regulates KrasG12D-induced skin tumorigenesis. J. Cell Biol, in press. ACTIVATING FG 2013-2014 Zhao L, Feng D, Bellile E and Taylor JMG. Bayesian Random Threshold Estimation in a Cox Proportional Hazards Cure Model. Statistics in Medicine, 33(4):650-661, 2014 Kiel MJ, Velusamy T, Rolland D, Sahasrabuddhe A, Chung F, Bailey N, Schrader A, Li B, Li J, Ozel A, Betz B, Miranda R, Medeiros LJ, Zhao L Herling M, Lim MS, Elenitoba-Johnson KS. Integrated Genomic Sequencing Reveals Mutational Landscape of T-cell Prolymphocytic Leukemia. Blood, 124(9):1460-72, 2014. Ilona I, Lin Y, Nagarsheth N, Peng D, Zhao L, Zhao E et al. IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity, 40(5):772-84, 2014. Lu JC, Connelly JA, Zhao L et al. Strain measurement by cardiovascular magnetic resonance in pediatric cancer survivors: Validation of feature tracking against harmonic phase imaging. Pediatric Radiology, 44: 1070-1076, 2014 Li H, Tan M, Jia L, Wei D, Zhao Y. Chen G. Xu J. Zhao L et al. Inactivation of SAG/RBX2 E3 ubiquitin ligase suppresses KrasG12D-driven tumorigenesis. The Journal of Clinical Investigation, 124(2):835-846, 2014 Cui T, Kryczek I, Zhao L, Zhao E, Kuick R, Roh M et al. Myeloid-derived suppressor cell (MDSC), immune suppression, microRNA, CtBP2, ovarian cancer and survival. Immunity, 39(3): 611-621, 2013 Engelke CG, Parsels LA, Qian Y, Zhang Q, Karnak D, Robertson JR, Wei D, Davis MA, Parsels JD, Tanska DM, Zhao L et al. Sensitization of pancreatic cancer to chemoradiation by the Chk1 inhibitor, MK8776. Clin Cancer Res, 19(16):4412-21, 2013. Last Updated: April 30, 2015 Page 4 VanderVeen N, Paran C, Krasinkiewicz J, Zhao L et al. Effectiveness and preclinical safety profile of doxycycline to be used “off-label” to induce therapeutic transgene expression in a Phase I clinical trial for glioma. Hum Gene Ther Clin Dev, 24(3):11626,2013 Hoodin F, Zhao L, Carey J, Levine JE, Kitko C. Impact of Psychological Screening on Routine Outpatient Care of Hematopoietic Cell Transplantation Survivors Biology of Blood and Marrow Transplantation. Biology of Blood and Marrow Transplantation, 19(10):1493-1497,2013 Wei D, Parsels LA, Karnak D, Davis MA, Parsels JD, Zhao L et al. Inhibition of protein phosphatase 2A radiosensitizes pancreatic cancers by modulating CDC25C/CDK1 and homologous recombination repair. Clin Cancer Res, 19(16):442232, 2013. 2012-2013 Sheetz KH, Zhao L, Holcombe SA, Wang SC, Reddy RM, Lin MB et al. Decreased core muscle size is associated with worse patient survival following esophagectomy for cancer. Dis Esophagus, 26(7):716-22, 2013 Jorns JM, Healy P and Zhao L. Review of Estrogen Receptor, Progesterone Receptor, and HER-2/neu Immunohistochemistry Impacts on Treatment for a Small Subset of Breast Cancer Patients Transferring Care to Another Institution. Arch Pathol Lab Med, 137(11):1660-3, 2013 Arps DP, Healy P, Zhao L, Kleer CG and Pang JC. Invasive ductal carcinoma with lobular features: a comparison study to invasive ductal and invasive lobular carcinomas of the breast. Breast Cancer Res Treat, 138(3):719-26, 2013 Zhao L, Taylor JMG, Schuetze SM. Bayesian decision theoretic two-stage design in Phase II clinical trials with survival endpoints, Statistics in Medicine 31(17):18041820, 2012 Venkatesha VA, Parsels LA, Parsels JD, Zhao L, Zabludoff SD, Simeone D et al. Sensitization of pancreatic cancer stem cells to gemcitabine by Chk1 inhibition. Neoplasia, 14:519-25, 2012. Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG , Chiang MY et al. Wholegenome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 209(9) 1553-65, 2012 Zhao L, Banerjee M. Bayesian piecewise mixture model for racial disparity in prostate cancer. Computational Statistics and Data Analysis 56(2):362-369, 2012 Schuetze SM, Zhao L, Chugh R et al. Results of a phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma. Eur J Cancer 48(9):1347-53, 2012 Teman N, Silski L, Zhao L, Kober M, Urba SC, Orringer MB et al. Thromboembolic Last Updated: April 30, 2015 Page 5 Events During Neoadjuvant Treatment of Esophageal Cancer Delay Time to Surgery. Ann Thorac Surg 94(4):1118-25, 2012 Kim SH, Chen G, King AN, Jeon CK, Christensen PJ, Zhao L et al. Characterization of Vitamin D Receptor (VDR) in Lung Adenocarcinama. Lung Cancer 2012. Wei DP, Li H, Yu J, Sebolt JT, Zhao L, Lawrence TS et al. Radiosensitization of human pancreatic cancer cells by MLN4924, an investigational NEDD8-activating enzyme inhibitor. Cancer Res. 72(1): 282-93, 2011. Vance S, Liu E, Zhao L, Parsels J, Parsels L, Brown J et al. Selective radiosensitization of p53 mutant pancreatic cancer cells by combined inhibition of Chk1 and PARP1. Cell Cycle, 10:4321-29, 2011. Zhao L, Lee J, Mody, R and Braun TM. The Superiority of the Time-to-Event Continual Reassessment Method to the Rolling Six Design in Pediatric Phase I Cancer Trials. Clinical Trials 8(4):361-369, 2011 Ray D, Ahsan A, Helman A, Chen G, Hegde A, Gurjar SR, Zhao L, Kiyokawa H, Beer DG, Lawrence TS, Nyati MK. Regulation of EGFR protein stability by the HECT-type ubiquitin ligase MURF2. Neoplasia,13(7):570-8, 2011 Parsels L, Qian Y, Tanska D, Gross M, Zhao L, Hassan M, et al. Chk1 phosphorylation as a pharmacodynamic biomarker of Chk1 inhibition. Clin Cancer Res, 17:3706-15, 2011. Bhojani MS, Nyati MK, Zhao L, Normolle, DP, Ross BD, Lawrence TS, Rehemtulla A. Molecular Imaging of Akt Enables Early Prediction of Response to Molecular Targeted Therapy. Transl Oncol 4(3): 122-125, 2011. Zhao L, Morgan MA, Parsels LA, et al. Response to Letter from Bassukas. Clinical Cancer Research 17: 4613, 2011 Lao CD, Johnson T, Sondak VK, Lowe L, Kim DS, Zhao L, Naftanel M, Olsen S, Brenner DE. Feasibility of serial biopsies of large dysplastic nevi as a melanoma chemoprevention model. J Am Acad Dermato 64(6):1188-90,2011 Davis SJ, Zhao L, Chang A and Orringer M. Refractory cervical esophagogastric anastomotic strictures: management and outcomes. Journal of Thoracic and Cardiovascular Surgery 141:444-448, 2011 Chen G, Kim SH, King A, Zhao L, et.al. CYP24A1 Is an Independent Prognostic Marker of Survival in Patients with Lung Adenocarcinoma. Clinical Cancer Research 17: 817-826, 2011 Tan L, Kwok RP, Shukla A, Kshirsagar M, Zhao L, et al. Trichostatin a restores Apaf1 function in chemoresistant ovarian cancer cells. Cancer 4: 784-794, 2011 Zhao L, Morgan MA, Parsels LA, et al. Bayesian Hierachical changepoint methods in modeling the tumor growth profiles in xenograft experiments. Clinical Cancer Research 17(5): 1-7, 2010 Last Updated: April 30, 2015 Page 6 Morgan MA, Parsles LA, Parsels JD, Davis MA, Hassan MC, Arumugarajah S, Hylander-Gans L, Morosini D, Zhao L, et al. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Research 70(12):4972-4981, 2010 Jing X, Roh, M, Knoepp S, Zhao L and Michael C. Follicular Lesion of Undetermined Significance and Identifying Predictive Features for Neoplasia. Diagnostic Cytopathology 2010 Ning W. and Zhao L. A moment-based test for the mixture distributions with small sample sizes and its application. Far East Journal of Theoretical Statistics. 33(1): 2329, 2010 Anderson M, Brenner D, Scheiman J, Simeone D, Singh N, Sikora M, Zhao L, Mertens A. Reliable gene expression measurements from endoscopic fine needle aspirates of pancreatic tumors: effect of amplicon length and quality assessment. Journal of Molecular Diagnostics 12(5): 566-575, 2010 Zhao L, Woodworth G. Bayesian Decision-Theoretic Group Sequential Analysis with Survival Endpoints. Statistics in Medicine 28:1339–1352, 2009 Stoffel E, Turgeon D, Stockwell D, Zhao L, et al. Missed Adenomas during Colonoscopic Surveillance in Individuals with Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer). Cancer Prevention Research 1, 470-475, 2008. Moon J, Kuehn D, Chen G, Zhao L. Induced Velopharyngeal Fatigue Effects in Speakers with Repaired Palatal Clefts. The Cleft Palate-Craniofacial Journal 44, 251260, 2007. Last Updated: April 30, 2015 Page 7