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

  • Ras nanoclusters: versatile lipid-based signaling platforms (2014) Zhou Y, Hancock JF. Biochim Biophys Acta, [Epub ahead of print Sep16]
  • Rare Streptomyces sp. polyketides as modulators of K-Ras localisation (2014) Salim AA, Xiao X, Cho KJ, Piggott AM, Lacey E, Hancock JF, Capon RJ. Org Biomol Chem. 12, 4872-4878
  • Signal integration by lipid-mediated spatial cross talk between Ras nanoclusters (2014) Zhou Y, Liang H, Rodkey T, Ariotti N, Parton RG, Hancock JF. Mol Cell Biol. 34, 862-876
  • Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling (2014) Ariotti N, Fernández-Rojo MA, Zhou Y, Hill MM, Rodkey T, Inder K, Hancock JF, Parton RG. J Cell Biol. 204, 777-792
  • Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function (2013) Hocker H, Cho KJ, Maharaja N, Stanslas J, Hancock JF, Gorfe AA. Proc Natl Acad Sci USA.110, 10201-10206
  • Fendiline inhibits K-Ras plasma membrane localization and blocks K-Ras signal transmission (2013) van der Hoeven D, Cho KJ, Ma X, Chigurupati S, Parton RG, Hancock JF. Mol Cell Biol. 33, 237-251
  • Staurosporines disrupt phosphatidylserine trafficking and mislocalize Ras proteins (2012) Cho KJ, Park JH, Piggott AM, Salim AA, Gorfe A, Parton RG, Capon RJ, Lacey E, Hancock JF. J Biol Chem. 287, 43573-43584
  • Structure-based reassessment of the caveolin signaling model: do caveolae regulate signaling through caveolin-protein interactions? (2012) Collins B, Davis MJ, Hancock JF, Parton RG. Dev Cell. 23, 11-20
  • Raf inhibitors dysregulate the spatiotemporal dynamics of Ras proteins on the plasma membrane (2012) Cho K-j, Kasai RS, Park J-H, Chigurupati S, Heidorn SJ, van der Hoeven D, Plowman SJ, Kusumi A, Marais R, Hancock JF. Curr Biol. 22, 945-955
  • Organization, dynamics and segregation of Ras nanoclusters in membrane domains (2012) Lanosi J, Li Z, Hancock JF, Gorfe AA. Proc Natl Acad Sci USA. 109, 8097-8102
  • Constitutive formation of caveolae in a bacterium (2012) Walser PJ, Ariotti N, Howes M, Ferguson C, Webb R, Schwudke D, Leneva N, Cho KJ, Cooper L, Rae J, Floetenmeyer M, Oorschot VM, Skoglund U, Simons K, Hancock JF, Parton RG. Cell.150, 752-763
  • Non-steroidal anti-inflammatory drugs alter the spatiotemporal organization of Ras proteins on the plasma membrane (2012) Zhou Y, Cho K-j, Plowman SJ, Hancock JF. J Biol Chem. 287, 16586-16595
  • The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes (2010) Zhou Y, Lichtenberger L, Hancock JF. J Biol Chem. 285, 35188-35195
  • EGFR activation remodels the plasma membrane lipid environment to induce nanocluster formation (2010)     Ariotti N, Liang H, Xu Y, Zhang Y, Yonekub Y, Inder K, Parton RG, Hancock JF, Plowman SJ. Mol Cell Biol. 30, 3795-3804
  • Signalling ballet in four dimensions (2010) Kholodenko BN, Hancock JF, Kolch W.     Nature Rev Mol Cell Biol. 11, 414-426
  • Membrane orientation and nanodomain localization generate Ras isoform diversity (2010) Abankwa D, Gorfe AA, Inder K, Hancock JF. Proc Natl Acad Sci USA. 107,1130-1135
  • Activation of the MAPK module from different spatial locations generates distinct system outputs (2008) Inder K, Harding A, Philips MR, Parton RG, Hancock JF. Mol Biol Cell. 19, 4776-4784
  • A novel switch region regulates H-ras membrane orientation and signal output (2008) Abankwa D, Hanzal-Bayer M, Ariotti N, Plowman SJ, Gorfe AA, Parton RG, McCammon JA, Hancock JF. EMBO J. 27, 727-735
  • PTRF, a novel, conserved caveolar coat protein that regulates caveolae formation and function (2008) Hill MH, Bastiani M, Luetterforst R, Kirkham M, Kirkham A, Nixon SJ, Walser P, Abankwa D, Oorschot VMJ, Martin S, Hancock JF, Parton RG. Cell. 132, 113-124
  • Plasma membrane nanoswitches generate high-fidelity Ras signal transduction (2007) Tian T, Harding A, Inder K, Plowman SJ, Parton RG, Hancock JF. Nature Cell Biol. 9, 905-914