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Research Interests:
Since 2003, Dr. Malehorn has performed development and implementation of proteomic profiling methods in the UPCI Clinical Proteomics Facility (CPF) (William L. Bigbee, Ph.D. and Thomas P. Conrads, Ph.D., Co-Directors), which serves and supports a broad range of translational research studies of basic science and clinician researchers across the UPCI and the Health Sciences at the University of Pittsburgh. Initial pilot biomarker discovery projects - profiling of archived biofluid specimens (serum, plasma, urine, etc) on the SELDI-ToF MS instrument platform - have led to follow-on studies with expanded and/or prospectively collected sample sets. These current studies are being transitioned into modified workflows on the Bruker ClinProt profiling system, which utilizes high-throughput sample processing, high-resolution MALDI-ToF MS and MS/MS, and integrated informatics to perform statistical classification. Dr. Malehorn also supports exploratory proteomics investigations of new biofluid or tissue sample types, including sample preparation, fractionation and separations (including gel-based) prior to profiling. Dr. Malehorn also supports analyte enrichment, biochemical purification, and protein identification in conjunction with an intersite collaboration between the CPF, the University of Pittsburgh Genomics and Proteomics Core Laboratories, and the Windber Research Institute. Dr. Malehorn continues an ongoing collaboration with University of Pittsburgh Departments of Biomedical Informatics and Computer Science, and extramural collaborators, with regard to the generation, preprocessing and statistical analysis of mass spectrometric profiling data. Dr. Malehorn is available for presentation and hands-on instruction in the CPF facility or in other classroom, meeting, or laboratory settings to discuss proteomic profiling, as well as data analysis and interpretation as currently being performed in the CPF.
Selected Publications:
Malehorn DE, Telmer CA, McEwen SB, An J, Kinsey AD, Retchless AC, Mason C, Vieta WM, Jarvik JW. Detection of cystic fibrosis mutations by peptide mass signature genotyping. Clin Chem 2003;49:1318-30.
Telmer CA, An J, Malehorn DE, Zeng X, Gollin SM, Ishwad CS, Jarvik JW. Detection and assignment of TP53 mutations in tumor DNA using peptide mass signature genotyping. Hum Mutat 2003;22:158-65.
R. Pelikan, M. Lotze, J. Lyons-Weiler, D. Malehorn, and M. Hauskrecht. Serum Proteomic Profiling and Analysis. In Lotze MT, Thomson AW, eds. Measuring Immunity: Basic Science and Clinical Practice, Elsevier, London, 2004.
Hauskrecht M, Pelikan R, Malehorn D, Bigbee WL, Lotze MT, Zeh HJ, III, Whitcomb DC, Lyons-Weiler J. Feature selection for classification of SELDI-TOF-MS proteomic profiles. Appl Bioinformatics 2005;4:227-46.
Lyons-Weiler J, Pelikan R, Hauskrecht M, Malehorn D, Bigbee WL. Assessing the statistical significance of the achieved classification error of classifiers constructed using serum peptide profiles, and a prescription for random sampling repeated studies for massive high-throughput genomic and proteomic studies. Cancer Informatics 2005;1:53-77.
Bigbee WL, Malehorn DE, El-Hefnawy T, Hauskrecht M, Lyons-Weiler J, Pelikan RC, Landreneau RJ, Luketich JD, Weissfeld JL, Siegfried JM (2005) Serum SELDI-TOF-MS protein expression profiling for lung cancer detection and classification. Presented at the 2005 Annual Meeting of the American Association for Cancer Research, Anaheim, CA. Proceedings of the American Association for Cancer Research 46 [Abstract 4797].
Miyamae T, Malehorn DE, Lemster B, Mori M, Imagawa T, Yokota S, Bigbee WL, Welsh MJ, Klarskov K, Nishomoto N, Vallejo AN, Hirsch R. Serum protein profile in systemic-onset juvenile idiopathic arthritis differentiates response versus non-response to therapy. Arthritis Res Ther 2005;7: R746-R755.
Dabbs DJ, El-Hefnawy T, Malehorn DE, Elbakri R, Bigbee WL. (2006) Tissue Fixation in Surgical Pathology for Proteome Analysis and Protein/DNA Preservation. Presented at 2006 Annual Meeting of the United States and Canadian Academy of Pathology, Atlanta GA, [abstract 1522]
Jahnukainen T, Malehorn D, Sun M, Lyons-Weiler J, Bigbee W, Gupta G, Shapiro R, Randhawa PS, Pelikan R, Hauskrecht M, Vats A. Proteomic analysis of urine in kidney transplant patients with BK virus nephropathy. J Am Soc Nephrol 2006;17:3248-56.
Malehorn DE, LaFramboise WA, Petrosko P, Jahnukainen T, Becich MJ and Bigbee WL. Trouble in Paradigm: Immunodepletion in Support of Proteomic Profiling and Biomarker Discovery. Presented at 2006 Clinical and Translational Science Day, University of Pittsburgh [Abstract 33].
Malehorn DE, Maity T, Leech BJ, Mural R, Shriver CD, Bassil F, Liebman MN, Kolli VSK, Bigbee WL (2006) Serum Fractionation in Support of Proteomic Profiling and Biomarker Discovery. Presented at Science2006 University of Pittsburgh, Pittsburgh PA. [Abstract 38].
Papachristou GI, Malehorn DE, Lamb J, Slivka A, Bigbee WL, Whitcomb DC. Serum proteomic patterns as a predictor of severity in acute pancreatitis. Pancreatology 2007 (accepted)
Malehorn DE, Dhir R, Chatta G, Bigbee WL. (2007) Divide and conquer: combined depletion and fractionation in support of plasma proteomic profiling. Presented at AACR Advances in Proteomics in Cancer Research, Amelia Island FL [abstract 36].
Malehorn DE, El-Hefnawy T, Landreneau RJ, Luketich JD, Sun M, Kaminski N, Rosas IO, Siegfried JM, Bigbee WL. Proteomic Profiling of Bronchoalveolar Lavage Fluid (BALF) As a Biofluid for the Detection of Lung Cancer. Abstract submitted to 2007 Annual Meeting of the American Society for Mass Spectrometry, Indianapolis IN.
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