Dr. John F. Hancock

Regular Member

The University of Texas Health Science Center at Houston
Medical School
Department of Integrative Biology & Pharmacology

Research Interests:

• Mammalian signal transduction
• Ras signaling
• Ras trafficking
• Cancer biology
• Plasma membrane structure and function
• Drug discovery

We are interested in signal transduction mechanisms that operate in mammalian cells. Our particular focus is centered on Ras GTPases that operate as membrane localized molecular switches in many signaling circuits. Understanding how Ras proteins signal is clinically relevant because of the high frequency of oncogenic mutations that target Ras directly, or other components of the Ras signaling network, in human cancer. Our most recent work has investigated how Ras proteins are organized on the plasma membrane, studies that have required the development of novel imaging methods and computational approaches to assay Ras function. Research themes in the laboratory are diverse, and include: investigation of the cell biology of Ras protein trafficking between the ER and plasma membrane, analysis of the molecular mechanisms that govern Ras interactions with the plasma membrane, proteomic and functional characterization of plasma membrane nanodomains, caveolae and lipid rafts, and mathematical modeling of Ras signaling networks. These research areas are among the most exciting and controversial in contemporary cell biology. A key aim of studying Ras biology and signaling is to identify novel approaches that could be used clinically to neutralize aberrant Ras function in cancer cells; genomic and chemical discovery programs therefore operate in parallel with all of our basic cell biology projects.

A tutorial in my laboratory includes an introduction to a variety of advanced imaging techniques such as confocal microscopy, FRET and FLIM imaging, TIRF microscopy and electron microscopy, as well as cellular and biochemical assays of signaling pathways, coupled with a firm grounding in basic cell and molecular biological methodologies that include cell culture and transfection, cell fractionation, immunoblotting, immunoprecipitation and protein purification. There are weekly lab meetings, group discussions and presentations.


Selected Publications:

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

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

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) Using plasma membrane nanoclusters to build better signaling circuits. Trends Cell Biol, 18,364-371

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, 615-61

Additional Publications

Program Affiliations:

Program in Cell and Regulatory Biology

Program in Experimental Therapeutics