Division of Biostatistics & Bioinformatics In the Department of Family Medicine and Public Health

Karen Messer, PhD

Professor & Division Chief

3855 Health Sciences Drive 0901
La Jolla, CA 92093-0901
858-822-4334
kmesser@ucsd.edu

http://biostats.mcc.ucsd.edu/

Dr. Karen Messer is Chief of the Division of Biostatistics and Bioinformatics at UCSD and has directed the Biostatistics Shared Resource at Moores UCSD Cancer Center since 2006. As an applied biostatistician, she has collaborated widely in academic medicine and in translational research, and as a mathematical statistician, she has developed new statistical tools and methods in genomic and biomarker studies. She has leadership experience within large collaborative research projects and statistical cores. She has designed many oncology trials, including validation studies for devices and prognostic biomarkers, and early phase therapeutic trials. Her current statistical research interests are in prognostic modeling and biomarker studies in cancer and with her colleague Loki Natarajan she is PI of an NCI-funded R01 to develop integrated genomic and behavioral risk models for breast cancer recurrence.

Principal Research Interests

  • High dimensional data analysis and genomic studies
  • Design and analysis of biomarker studies
  • Clinical trial design in oncology
  • Epidemiology of tobacco use
  • Prognostic modeling

A Complete List of her Published Work


http://www.ncbi.nlm.nih.gov/myncbi/karen.messer.1/bibliography/45282048/public/?sort=date&direction=descending

Statistical methods and tools:

Dr. Messer has published fundamental studies in mathematical statistics. However, new statistical tools and methods often arise from translational studies. She has contributed tools for next-gen sequencing data and methods of adjustment for measurement error, has clarified the FDR rate of common approaches to validation studies in genomics and established the properties of resampling- based variance estimates which are widely used bioinformatics and statistics. In this work, her training in mathematical statistics is often useful.

  • Natarajan L, Pu M, Messer K. Exact statistical tests for the intersection of independent lists of genes. Ann Appl Stat. 2012 Jun;6(2):521-541. PubMed PMID: 23335952; PubMed Central PMCID: PMC3546508.
  • Messer K, Natarajan L. Maximum likelihood, multiple imputation and regression calibration for measurement error adjustment. Stat Med. 2008 Dec 30;27(30):6332-50. PubMed PMID: 18937275; PubMed Central PMCID: PMC2630183.
  • Messer K, Gamst A. The asymptotic distribution of the delete-d Jackknife variance estimator for smooth functionals. Journal of statistical planning and inference. 2008; 138:2154-2162.
  • Messer K, Goldstein L. A new class of kernels for nonparametric curve estimation. Annals of statistics. 1993; 21:179 - 195.

Genomic studies in cancer:

New assays and experimental systems are rapidly increasing our knowledge of cancer etiology and progression. These new methods bring important statistical and data analysis challenges, for example control of the error rate in ultra deep sequencing studies, and avoiding false positives in multiplexed biomarker assays. Classical statistical issues become even more important, such as control of confounding in discovery studies from human specimens, efficient experimental designs in animal studies with transgenic mice, and proper comparison of survival experience by transcript expression levels in post hoc analyses.

  • Smith EN, Ghia EM, DeBoever CM, Rassenti LZ, Jepsen K, Yoon KA, Matsui H, Rozenzhak S, Alakus H, Shepard PJ, Dai Y, Khosroheidari M, Bina M, Gunderson KL, Messer K, Muthuswamy L, Hudson TJ, Harismendy O, Barrett CL, Jamieson CH, Carson DA, Kipps TJ, Frazer KA. Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development. Blood Cancer J. 2015 Apr 10;5:e303. PubMed PMID: 25860294; PubMed Central PMCID: PMC4450323
  • Cui B, Chen L, Zhang S, Mraz M, Fecteau JF, Yu J, Ghia EM, Zhang L, Bao L, Rassenti LZ, Messer K, Calin GA, Croce CM, Kipps TJ. MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia. Blood. 2014 Jul 24;124(4):546-54. PubMed PMID: 24914134; PubMed Central PMCID: PMC4110661.
  • Barnhill LM, Williams RT, Cohen O, Kim Y, Batova A, Mielke JA, Messer K, Pu M, Bao L, Yu AL, Diccianni MB. High expression of CAI2, a 9p21-embedded long noncoding RNA, contributes to advanced-stage neuroblastoma. Cancer Res. 2014 Jul 15;74(14):3753-63. PubMed PMID: 25028366; PubMed Central PMCID: PMC4126165.
  • Harismendy O, Schwab RB, Bao L, Olson J, Rozenzhak S, Kotsopoulos SK, Pond S, Crain B, Chee MS, Messer K, Link DR, Frazer KA. Detection of low prevalence somatic mutations in solid tumors with ultra-deep targeted sequencing. Genome Biol. 2011 Dec 20;12(12):R124. PubMed PMID: 22185227; PubMed Central PMCID: PMC3334619.

Prognostic modelling, biomarkers, and risk assessment:

Important statistical issues in risk modeling include strategies for control of optimism in assessing the prediction error rate, rigorous model development and independent validation, adjustment for bias and confounding in non-experimental systems, and quantification of prognostic benefit using clinically relevant measures.

  • Baumgartner JM, Kwong TG, Ma GL, Messer K, Kelly KJ, Lowy AM. A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol. 2015 Dec 17;PubMed PMID: 26678406.
  • Bao L, Messer K, Schwab R, Harismendy O, Pu M, Crain B, Yost S, Frazer KA, Rana B, Hasteh F, Wallace A, Parker BA. Mutational Profiling Can Establish Clonal or Independent Origin in Synchronous Bilateral Breast and Other Tumors. PLoS One. 2015;10(11):e0142487. PubMed PMID: 26554380; PubMed Central PMCID: PMC4640562.
  • Martínez ME, Thompson P, Messer K, Ashbeck EL, Lieberman DA, Baron JA, Ahnen DJ, Robertson DJ, Jacobs ET, Greenberg ER, Cross AJ, Atkin W. One-year risk for advanced colorectal neoplasia: U.S. versus U.K. risk-stratification guidelines. Ann Intern Med. 2012 Dec 18;157(12):856-64. PubMed PMID: 23247939; PubMed Central PMCID: PMC3787691.
  • Zhang L, Murray F, Rassenti LZ, Pu M, Kelly C, Kanter JR, Greaves A, Messer K, Kipps TJ, Insel PA. Cyclic nucleotide phosphodiesterase 7B mRNA: an unfavorable characteristic in chronic lymphocytic leukemia. Int J Cancer. 2011 Sep 1;129(5):1162-9. PubMed PMID: 21120911; PubMed Central PMCID: PMC3111850.

Drug discovery and mechanism of action studies:

High throughput molecular screening and highly multiplexed assays of experimental differences in transcription products, protein expression, or immune cell populations are common in drug development studies. Dr Messer has contributed to the design and analysis of complex experiments in this setting, in animal models, in vitro screens and clinical samples.

  • Goff DJ, Court Recart A, Sadarangani A, Chun HJ, Barrett CL, Krajewska M, Leu H, Low-Marchelli J, Ma W, Shih AY, Wei J, Zhai D, Geron I, Pu M, Bao L, Chuang R, Balaian L, Gotlib J, Minden M, Martinelli G, Rusert J, Dao KH, Shazand K, Wentworth P, Smith KM, Jamieson CA, Morris SR, Messer K, Goldstein LS, Hudson TJ, Marra M, Frazer KA, Pellecchia M, Reed JC, Jamieson CH. A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition. Cell Stem Cell. 2013 Mar 7;12(3):316-28. PubMed PMID: 23333150; PubMed Central PMCID: PMC3968867.
  • Chan M, Hayashi T, Mathewson RD, Nour A, Hayashi Y, Yao S, Tawatao RI, Crain B, Tsigelny IF, Kouznetsova VL, Messer K, Pu M, Corr M, Carson DA, Cottam HB. Identification of substituted pyrimido[5,4-b]indoles as selective Toll-like receptor 4 ligands. J Med Chem. 2013 Jun 13;56(11):4206-23. PubMed PMID: 23656327; PubMed Central PMCID: PMC3722616.
  • Widhopf GF 2nd, Cui B, Ghia EM, Chen L, Messer K, Shen Z, Briggs SP, Croce CM, Kipps TJ. ROR1 can interact with TCL1 and enhance leukemogenesis in Eμ-TCL1 transgenic mice. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):793-8. PubMed PMID: 24379361; PubMed Central PMCID: PMC3896194.
  • Goff PH, Hayashi T, Martínez-Gil L, Corr M, Crain B, Yao S, Cottam HB, Chan M, Ramos I, Eggink D, Heshmati M, Krammer F, Messer K, Pu M, Fernandez-Sesma A, Palese P, Carson DA. Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine adjuvants induce rapid, sustained, and broadly protective responses. J Virol. 2015 Mar;89(6):3221-35. PubMed PMID: 25568203; PubMed Central PMCID: PMC4337541.

Development of molecularly targeted imaging agents:

UCSD is fortunate to have several groups working in this fast developing area. Dr Messer has contributed to design and analysis of experimental and clinical studies over a number of years with several of these groups. Considerable care is often needed in order to quantify improvement over standard of care, using these novel agents.

  • Baker JL, Pu M, Tokin CA, Hoh CK, Vera DR, Messer K, Wallace AM. Comparison of [(99m)Tc]tilmanocept and filtered [(99m)Tc]sulfur colloid for identification of SLNs in breast cancer patients. Ann Surg Oncol. 2015 Jan;22(1):40-5. PubMed PMID: 25069859; PubMed Central PMCID: PMC4273083.
  • Hussain T, Mastrodimos MB, Raju SC, Glasgow HL, Whitney M, Friedman B, Moore JD, Kleinfeld D, Steinbach P, Messer K, Pu M, Tsien RY, Nguyen QT. Fluorescently labeled peptide increases identification of degenerated facial nerve branches during surgery and improves functional outcome. PLoS One. 2015;10(3):e0119600. PubMed PMID: 25751149; PubMed Central PMCID: PMC4353702.
  • Hussain T, Savariar EN, Diaz-Perez JA, Messer K, Pu M, Tsien RY, Nguyen QT. Surgical molecular navigation with ratiometric activatable cell penetrating peptide for intraoperative identification and resection of small salivary gland cancers. Head Neck. 2014 Dec 18;PubMed PMID: 25521629; PubMed Central PMCID: PMC4472578.
  • Tran Cao HS, Kaushal S, Metildi CA, Menen RS, Lee C, Snyder CS, Messer K, Pu M, Luiken GA, Talamini MA, Hoffman RM, Bouvet M. Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy in an orthotopic model of pancreatic cancer. Hepatogastroenterology. 2012 Sep;59(118):1994-9. PubMed PMID: 22369743; PubMed Central PMCID: PMC4096574.

Epidemiology of tobacco use behaviors:

Tobacco use remains the leading cause of preventable death in the developed world. Population attitudes have become less tolerant of tobacco use and more supportive of effective tobacco control policies, such as smoke-free laws and high excise taxes. Along with advertising restrictions on cigarette marketing to youth, these changes have led to decreased smoking initiation and increased cessation. However, smoking rates remain high especially among disadvantaged populations. There is also increased and unrestricted marketing of new tobacco products and the regulation of tobacco is now under the authority of the FDA. Population surveillance of tobacco use remains critically important in order to inform effective tobacco control policy and new tobacco regulation.

  • Pierce JP, Messer K, James LE, White MM, Kealey S, Vallone DM, Healton CG. Camel No. 9 cigarette-marketing campaign targeted young teenage girls. Pediatrics. 2010 Apr;125(4):619-26. PubMed PMID: 20231181.
  • Pierce JP, Messer K, White MM, Kealey S, Cowling DW. Forty years of faster decline in cigarette smoking in California explains current lower lung cancer rates. Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2801-10. PubMed PMID: 20852009.
  • Pierce JP, Cummins SE, White MM, Humphrey A, Messer K. Quitlines and nicotine replacement for smoking cessation: do we need to change policy?. Annu Rev Public Health. 2012 Apr;33:341-56. PubMed PMID: 22224888.
  • Messer K, White MM, Strong DR, Wang B, Shi Y, Conway KP, Pierce JP. Trends in use of little cigars or cigarillos and cigarettes among U.S. smokers, 2002-2011. Nicotine Tob Res. 2015 May;17(5):515-23. PubMed PMID: 25239955; PubMed Central PMCID: PMC4402355.

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