The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 John F. Hancock, MA, MB, BChir, PhD, ScD

John F. Hancock, MA, MB, BChir, PhD, ScD

Vice-Dean of Research
Executive Director, Institute of Molecular Medicine,
Professor and Chairman, Dept Integrative Biology and Pharmacology
John S Dunn Distinguished University Chair in Physiology and Medicine

John.F.Hancock@uth.tmc.edu

713-500-2401

John F. Hancock was appointed Chairman of Integrative Biology and Pharmacology at the University of Texas Medical School in July 2008 and Vice-Dean of Research and Executive Director of the Institute of Molecular Medicine in July 2012.  Dr. Hancock also holds the Fondren Chair in Cellular Signaling. He is a fellow of the Royal Australian College of Physicians and a member of The Royal College of Physicians (UK).  Dr. Hancock was formerly Deputy Director of the Institute for Molecular Bioscience, University of Queensland, one of Australia’s premier biomedical Research Institutes and Director of the Australian Research Council’s Special Research Center for Functional and Applied Genomics. He was also on the faculty of the University of Queensland as a professor of molecular cell biology and professor of experimental oncology. Before moving to Australia in 1995, he was a Research Director at Onyx Pharmaceuticals, a biotech company in California. Dr. Hancock read Natural Sciences and Medicine at the University of Cambridge, UK from 1975-1981 before embarking on the US equivalent of internal medicine and then hematology/ oncology residency programs at major London teaching hospitals. He started his scientific training in 1986 as an MRC Research Fellow at the Institute of Cancer Research, London, from where he received his PhD. In 1989 Dr. Hancock set up his first research laboratory at the Royal Free Hospital, London where he also practiced as a Consultant Hematologist until leaving the UK in 1992.

Research Interests

Dr. Hancock’s laboratory studies basic mechanisms of mammalian cell signaling. He is especially interested in the function of Ras proteins. These small GTP binding proteins operate as molecular switches in signal transduction pathways and are present in a mutant, activated state in many human tumors. Understanding the basic biology of Ras has major implications for the development of novel anticancer therapeutics. The laboratory uses advanced live cell imaging, electron microscopy, proteomics and mathematical modeling to study how the Ras membrane anchors cooperate with the G-domain and peptide sequences flanking the anchor to drive lateral segregation into dynamic nanodomains, called nanoclusters. This work has generated new models of how lipidated proteins interact with, and use, the plasma membrane to generate signaling platforms and has revealed how the confinement of signaling complexes in plasma membrane nanodomains regulates the kinetics, sensitivity and fidelity of signal transmission. Related projects are focused on characterizing the mechanisms whereby K-ras, the Ras that protein that drives the largest number of human tumors, is transported to the plasma membrane after posttranslational processing on the endoplasmic reticulum. Recent novel insights from these basic scientific programs have been translated into drug discovery programs.  

Selected recent publications

  • Cho K-j, Hill MH, Chigurupati S, Du G, Parton RG, Hancock JF (2011) Therapeutic levels of the HMG-CoA reductase inhibitor lovastatin activate Ras signaling via phospholipase D2. Mol Cell Biol. in press
  • Zhou Y, Lichtenberger L, Hancock JF (2010) The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes. J Biol Chem. 285, 35188-35195
  • Howes MT, Kirkham M, Riches J, Cortese K, Walser PJ, Simpson F, Hill MM, Jones A, Lundmark R, Lindsay MR, Hernandez-Deviez DJ, Hadzic G, McCluskey A, Bashir R, Liu L, Pilch P, McMahon H, Robinson PJ, Hancock JF, Mayor S, Parton RG.(2010) Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. J Cell Biol. 190, 675-91
  • Crouthamel M, Abankwa D, Zhang L, Dilizio C, Manning DR, Hancock JF, Wedegaertner PB (2010) An N-terminal polybasic motif of Gaq is required for signaling and influences membrane nanodomain distribution. Mol Pharmacol. 78, 767-777
  • Rotblat B, Belanis L, Hancock JF, Kloog Y, Plowman SJ (2010) H-Ras nanocluster stability regulates the magnitude of MAPK signal output. PLoS One. 5, e11991
  • Ariotti N, Liang H, Xu Y, Zhang Y, Yonekub Y, Inder K, Parton RG, Hancock JF, Plowman SJ (2010) EGFR activation remodels the plasma membrane lipid environment to induce nanocluster formation. Mol Cell Biol. 30, 3795-3804
  • Kholodenko BN, Hancock JF, Kolch W (2010) Signalling ballet in four dimensions. Nature Rev Mol Cell Biol. 11, 414-426
  • Tian T, Plowman SJ, Parton RG, Kloog Y, Hancock JF (2010) Mathematical modeling of K-Ras nanocluster formation on the plasma membrane. Biophys J. 99, 534-543
  • Zhou Y, Hancock JF, Lichtenberger L (2010) Nonsteroidal anti-inflammatory drug indomethacin induces phase heterogeneity in mixed lipid membranes: potential implication for its diverse biological actions. PLoS One. 5, e8811
  • Abankwa D, Gorfe AA, Inder K, Hancock JF (2010) Membrane orientation and nanodomain localization generate Ras isoform diversity. Proc Natl Acad Sci USA. 107,1130-1135
  • Kiskowski MA, Hancock JF, Kenworthy AK (2009) On the use of Ripley's K-function and its derivatives to analyze domain size. Biophys J. 97,1095-103
  • Bastiani M, Liu L, Hill MH, Jedrychowski MP, Nixon SJ, Lo HP, Abankwa D, Luetterforst R, Fernandez-Rojo, Breen MR, Steven P, Gygi SP, Vinten J, Walser PJ, North KN, Hancock JF, Pilch PF, Parton RG (2009) MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes. J Cell Biol. 185, 1259-1273
  • Inder K, Lau C, Loo, Chaudhary N, Goodall A, Martin S, Jones A, Parton RG, Hill M, Hancock JF (2009) Nucleophosmin and nucleolin regulate K-Ras plasma membrane interactions and MAPK signal transduction. J Biol Chem. 284, 28410-28419
  • Abankwa D, Gorfe AA, Hancock JF (2008) Mechanisms of Ras membrane organization and signaling: Ras on a rocker. Cell Cycle. 7, 2667-2673
  • Inder K, Harding A, Philips MR, Parton RG, Hancock JF (2008) Activation of the MAPK module from different spatial locations generates distinct system outputs. Mol Biol Cell. 19, 4776-4784
  • Shalom-Feuerstein R, Plowman SJ, Rotblat B, Ariotti N, Tian T, Hancock JF and Kloog Y (2008) K-Ras nanoclustering is subverted by over-expression of the scaffold protein galectin-3. Cancer Res. 68, 6608-6616
  • Harding, A and Hancock JF (2008) Using plasma membrane nanoclusters to build better circuits. Trends Cell Sci. 18, 364-371
  • Plowman SJ, Ariotti N, Parton RG, Hancock JF (2008) Electrostatic interactions positively regulate K-Ras nanocluster formation and function. Mol Cell Biol. 28, 4377-4385
  • Rowlinson SW, Yoshizato H, Barclay JL, Brooks AJ, Behncken SN, Kerr LM, Millard K, Palethorpe K, Nielsen K, Clyde-Smith J, Hancock JF, Waters MJ (2008) An agonist-induced conformational change in the Growth Hormone receptor determines choice of signalling pathway. Nature Cell Biol. 10, 740-747
  • Abankwa D, Hanzal-Bayer M, Ariotti N, Plowman SJ, Gorfe AA, Parton RG, McCammon JA, Hancock JF (2008) A novel switch region regulates H-ras membrane orientation and signal output.  EMBO J. 27, 727-735
  • Belanis L, Plowman SJ, Rotblat B, Hancock JF, Kloog Y (2008) Galectin-1 is a novel structural component and major regulator of H-ras nanoclusters. Mol Biol Cell. 19, 1404-1414v
  • Hill MH, Bastiani M, Luetterforst R, Kirkham M, Kirkham A, Nixon SJ, Walser P, Abankwa D, Oorschot VMJ, Martin S, Hancock JF, Parton RG (2008) PTRF, a novel, conserved caveolar coat protein that regulates caveolae formation and function. Cell. 132, 113-124
  • Harding A and Hancock JF (2008) Ras nanoclusters: combining digital and analog signaling. Cell Cycle. 7, 127-134
  • Tian T, Harding A, Inder K, Plowman SJ, Parton RG, Hancock JF (2007) Plasma membrane nanoswitches generate high-fidelity Ras signal transduction. Nature Cell Biol. 9, 905-914
  • Hancock JF (2007) PA promoted to manager. Nature Cell Biol. 9, 615-617