Proteomic Analysis of Pathways Involved in Hematophoeisis and Leukaemic Transformation
Conference Recording Oct 07, 2013
About the Speaker
Professor Tony Whetton is Vice Dean and Deputy Head of the Faculty of Medical and Human Sciences at the University of Manchester. He is currently systematically defining the downstream proteomic and phosphoproteomic effects of the protein tyrosine kinases associated with myeloproliferative disorders and myeloid leukaemias to discover common mechanisms for leukaemic transformation. He is also Adjunct Professor in the Department of Gene and Cell Medicine at Mount Sinai School of Medicine in New York, USA where he works with the Black Family Stem Cell Institute, using proteomics to define embryonic stem cell differentiation control.
AbstractProteomic approaches have been employed to gain new insights into hematopoietic cell development. These approaches include isobaric tagging of peptides to offer 4 or 8 channel sample runs. Relative quantification of many proteins and their changes during differentiation or leukaemogenic protein tyrosine kinase mediated transformation has been achieved and comparison with cellular changes in mRNA performed. This has shown the critical importance of regulation at the protein level in hematopoietic cell development and the processes of leukaemic transformation. Based on these data novel features of protein tyrosine kinase mediated oncogenesis have been uncovered in both cell line models and highly enriched primitive hematopoietic cells. Based on these findings and a multiple reaction monitoring based mass spectrometry approach to phosphorylation site analysis on key proteins, a pathway for regulation of mRNA translation affected by extracellular agonists and growth factors, stress and leukaemogenic protein tyrosine kinases linking to mRNA translation modulation is being elucidated.