William A. LaFramboise, PhD
Associate Professor of Pathology
Dr. LaFramboise is a member of the Division of Anatomic Pathology, the Division of Molecular Anatomic Pathology, and the University of Pittsburgh Cancer Institute. He directs the Genomics Division of the Cancer Biomarker Facility.
Pittsburgh, PA 15232
Office Telephone: 412-623-6160
Genomics Lab: 412-623-1497
Sequencing Lab: 412-864-7515
Stem Cell Lab: 412-623-7903
Molecular Diagnosis and Etiology of GU CancersHigh density genome-wide SNP profiles generated on five classifications of renal cell carcinoma (RCC) have led to the identification of prospective tumor type-specific genomic biomarkers. Whole genome sequencing and targeted chromosome 9 resequencing studies are ongoing to validate RCC tumor-type specific signatures using SOLiD and Ion Torrent platforms. We are also testing for the presence of tumor stem cells underlying prostate tumorigenesis. An in vitro assay is utilized to identify stem cells intrinsic to normal tissues and tumors of the prostate gland. Currently, DNA, mRNA and miRNA harvested from stem, stromal and epithelial cells from prostate biopsies purified in vitro reveal cell type-specific changes in profiles of the mRNA and miRNA transcriptome. These classification signatures are being tested for efficacy as a biopsy biomarker in PCR based assays of prostate tumors.
Myocardial Repair and Detection of Coronary Artery DiseaseWe identified factors secreted from embryonic stem cells that activate proliferation of neonatal cardiomyocytes in vitro through the RhoA, RAC1 and Jak-Stat pathways. Additional studies demonstrated that cardiac fibroblasts block the proliferative behavior of neonatal cardiomyocytes in culture by production of cytokines associated with the TGF-beta pathway. These data suggest that cardiomyocytes may be influenced by paracrine factors to adopt phenotypic behavior supporting scarification or regeneration. Targeted proteomics studies are currently underway using the Aushon Immunoassay system to determine combinatorial serum protein profiles in patients that reveal the presence of coronary artery disease (CAD) prior to infarct. Significant differences in circulating proteins from patients with CAD requiring revascularization included increased APO-B100, CRP, fibrinogen, VCAM-1, MPO, resistin, osteopontin, IL-6, IL-1β , IL-10 and NT-pBNP and decreased APO-A1.
High Throughput Genomics and Proteomics: Clinical Genomics, Immunogeneomics, and Sequencing FacilitiesGeneration of genome-wide DNA, mRNA and microRNA profiles is routinely performed with microarrays using probe specific hybridization kinetics or primer driven assays. Dr. LaFramboise is responsible for the selection, design, calibration, optimization, and performance of all assays in the research service facilities including interrogation of genome-wide DNA, mRNA and microRNA profiles in human cancer specimens using 1) microarrays employing probe specific hybridization (Affymetrix, CodeLink, Exiqon), 2) PCR based primer driven amplification assays (7900 HT-qrtPCR), and 3) massively parallel sequencing of whole human genome, exomes and targeted regions (SOLiD, Ion Torrent). We have compiled an internal normal DNA and SNP reference database for utilization in all SNP and sequencing studies. We also assist with statistical analysis of data generated within the facility. Secure client database access is provided over the primary server and laboratory information system (LIMS: DS3400 IBM SAS external storage and Windows Enterprise server).
Genomics Facility: http://www.upci.upmc.edu/cbf/index.cfm; 412-623-1497. Sequencing Facility: 412-864-7515.
Recent Peer-Reviewed PublicationsView Dr. LaFramboise's publications on PubMed
LaFramboise WA, Jayaraman RC, Bombach KL, Ankrapp DP, Krill-Burger JM, Sciulli CM, Petrosko P, Wiseman RW. Acute molecular response of mouse hindlimb muscles to chronic stimulation. Am J Physiol Cell Physiol. 2009 Sep;297(3):C556-70. Epub 2009 Jul 22.
Krill-Burger JM, Lyons MA, Kelly LA, Sciulli CM, Patricia Petrosko P, Chandran UR, Kubal MD, Bastacky SI, Parwani AV, Dhir R, LaFramboise WA. Renal Cell Neoplasms Contain Shared Tumor Type-Specific Copy Number Variations. American Journal of Pathology. (in press).
Yu YP, Song C, Tseng G, Ren BG, LaFramboise W, Michalopoulos G, Nelson J, Luo JH. Genome abnormalities precede prostate cancer and predict clinical relapse. Am J Pathol. 2012 Jun: 180(6):2240-2248.
Satish L, LaFramboise WA, Johnson S, Vi L, Njarlangattil A, Raykha C, Krill-Burger JM, Gallo PH, O'Gorman DB, Gan BS, Baratz ME, Ehrlich GD, Kathju S. Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture. BMC Med Genomics. 2012 May: (4): 5:15.
Manohar R, Komori J, Guzik L, Stolz DB, Chandran UR, LaFramboise WA, Lagasse E. Identification and expansion of a unique stem cell population from adult mouse gallbladder. Hepatology. 2011 Jul 25. doi: 10.1002/hep.24568.
Lisovich A, Chandran UR, Lyons-Weiler MA, LaFramboise WA, Brown AR, Jakacki RI, Pollack IF, Sobol RW. A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples. BMC Med Genomics. 2011 Jan 26;4(1):14.
Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Holmes EJ, Zhou T, Jakacki RI; Children's Oncology Group. IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group. Childs Nerv Syst. 2011 Jan;27(1):87-94.
LaFramboise WA, Petrosko P, Krill-Burger JM, Morris DR, McCoy AR, Scalise D, Malehorn DE, Guthrie RD, Becich MJ, Dhir R. Proteins secreted by embryonic stem cells activate cardiomyocytes through ligand binding pathways. J Proteomics. 2010 Mar 10;73(5):992-1003.
LaFramboise WA, Jayaraman RC, Bombach KL, Ankrapp DP, Krill-Burger JM, Sciulli CM, Petrosko P, Wiseman RW. Acute molecular response of mouse hindlimb muscles to chronic stimulation. Am J Physiol Cell Physiol. 2009 Sep;297(3):C556-70.