Dean Billheimer

Photo of Dean Billheimer

Dean Billheimer

Professor, Public Health
Director, Statistical Consulting
Professor, Statistics-GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Epidemiology and Biostatistics
Department Affiliations
Epidemiology and Biostatistics
BIO5 Institute
Contact
(520) 626-9902
dean.billheimer@arizona.edu

Work Summary

My research develops new clinical trial and experimental study designs to allow 'learning from data' more efficiently. My research also develops new analysis methods to understand latent structure in data. This allows better understanding of disease processes, better targeting of existing treatments, and development of more effective new treatments. Finally, I am developing new statistical methods based on prediction of future events.

Research Interest

Dean Billheimer, PhD, works with the Arizona Statistics Consulting Laboratory (StatLab) to partner with scientists and physicians to advance discovery and understanding. The 'Stat Lab' provides statistical expertise, personnel and computing resources to facilitate study design and conduct, data acquisition protocols, data analysis, and the preparation of grants and manuscripts. Dr. Billheimer also works to adapt and develop new statistical methods to address emerging problems in science and medicine. Dr. Billheimer facilitates discovery translation and economic development by consulting with public and private organizations external to the University of Arizona. Keywords: Biostatistics, Bioinformatics, Study Design, Bayesian Analysis

Publications

Xu, H., Radabaugh, T., Lu, Z., Galligan, M., Billheimer, D., Vercelli, D., Wright, A. L., Monks, T. J., Halonen, M., & Lau, S. S. (2016). Exploration of early-life candidate biomarkers for childhood asthma using antibody arrays. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 27(7), 696-701.

Proteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.

Zhang, H., Liu, Q., Zimmerman, L., Ham, A., Slebos, R., Rahman, J., Kikuchi, T., Massion, P., Carbone, D., Billheimer, D., & Liebler, D. (2011). Methods for peptide and protein quantitation by liquid chromatography-multiple reaction monitoring mass spectrometry. Mol Cell Proteomics, 10(6).

M110.006593 ; PMID: 21357624

Yang, L., Amann, J. M., Kikuchi, T., Porta, R., Guix, M., Gonzalez, A., Park, K., Billheimer, D., Arteaga, C. L., Tai, H., DuBois, R., Carbone, D. P., & Johnson, D. H. (2007). Inhibition of epidermal growth factor receptor signaling elevates 15-hydroxyprostaglandin dehydrogenase in non-small-cell lung cancer. Cancer Research, 67(12), 5587-5593.

PMID: 17575121;Abstract:

Evidence indicates that the induction of cyclooxygenase-2 (COX-2) and high prostaglandin E2 (PGE2) levels contribute to the pathogenesis of non-small-cell lung cancer (NSCLC). In addition to overproduction by COX-2, PGE2 concentrations also depend upon the levels of the PGE2 catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH). We find a dramatic down-regulation of PGDH protein in NSCLC cell lines and in resected human tumors when compared with matched normal lung. Affymetrix array analysis of 10 normal lung tissue samples and 49 resected lung tumors revealed a much lower expression of PGDH transcripts in all NSCLC histologic groups. In addition, treatment with the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) erlotinib increased the expression of 15-PGDH in a subset of NSCLC cell lines. This effect may be due in part to an inhibition of the extracellular signal-regulated kinase (ERK) pathway as treatment with mitogen-activated protein kinase kinase (MEK) inhibitor U0126 mimics the erlotinib results. We show by quantitative reverse transcription-PCR that the transcript levels of ZEB1 and Slug transcriptional repressors are dramatically reduced in a responsive cell line upon EGFR and MEK/ERK inhibition. In addition, the Slug protein, but not ZEB1, binds to the PGDH promoter and represses transcription. As these repressors function by recruiting histone deacetylases to promoters, it is likely that PGDH is repressed by an epigenetic mechanism involving histone deacetylation, resulting in increased PGE 2 activity in tumors. This effect is reversible in a subset of NSCLC upon treatment with an EGFR TKI. ©2007 American Association for Cancer Research.

Koska, J., Yassine, H., Trenchevska, O., Sinari, S., Schwenke, D. C., Yen, F. T., Billheimer, D., Nelson, R. W., Nedelkov, D., & Reaven, P. D. (2016). Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes. Journal of lipid research, 57(5), 894-905.

The apoC-III proteoform containing two sialic acid residues (apoC-III2) has different in vitro effects on lipid metabolism compared with asialylated (apoC-III0) or the most abundant monosialylated (apoC-III1) proteoforms. Cross-sectional and longitudinal associations between plasma apoC-III proteoforms (by mass spectrometric immunoassay) and plasma lipids were tested in two randomized clinical trials: ACT NOW, a study of pioglitazone in subjects with impaired glucose tolerance (n = 531), and RACED (n = 296), a study of intensive glycemic control and atherosclerosis in type 2 diabetes patients. At baseline, higher relative apoC-III2 and apoC-III2/apoC-III1 ratios were associated with lower triglycerides and total cholesterol in both cohorts, and with lower small dense LDL in the RACED. Longitudinally, changes in apoC-III2/apoC-III1 were inversely associated with changes in triglycerides in both cohorts, and with total and small dense LDL in the RACED. apoC-III2/apoC-III1 was also higher in patients treated with PPAR-γ agonists and was associated with reduced cardiovascular events in the RACED control group. Ex vivo studies of apoC-III complexes with higher apoC-III2/apoC-III1 showed attenuated inhibition of VLDL uptake by HepG2 cells and LPL-mediated lipolysis, providing possible functional explanations for the inverse association between a higher apoC-III2/apoC-III1 and hypertriglyceridemia, proatherogenic plasma lipid profiles, and cardiovascular risk.

Yassine, H. N., Trenchevska, O., Ramrakhiani, A., Parekh, A., Koska, J., Walker, R. W., Billheimer, D., Reaven, P. D., Yen, F. T., Nelson, R. W., Goran, M. I., & Nedelkov, D. (2015). The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides. PloS one, 10(12), e0144138.

Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations.

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