Alistair Hume

Contact

• workRoom D77 Medical School, QMC
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work01158230102
• fax01158230142
• Alistair.Hume@nottingham.ac.uk
• http://www.nottingham.ac.uk/biomedsci/people/school-directory/Alistair.Hume

Research Summary

Cells are fundamental units of the body and their correct function is vital for our health and survival. My research focuses on understanding how cells organise the complex array of internal… read more

Selected Publications

• OSTROWSKI M, CARMO NB, KRUMEICH S, RAPOSO G, SAVINA A, MOITA CF, FREITAS RP, SCHAUER K, GOUD B, BENAROCHE P, HUME AN, SEABRA MC, HACOHEN N, AMIGORENA S, MOITA LF, THERY, C, 2010. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 12, 19-30
• NIGHTINGALE TD, PATTNI K, HUME AN, SEABRA MC, CUTLER DF., 2009. Rab27a and Myrip regulate the amount and multimeric state of vWF released from endothelial cells. Blood. 113, 5010-8
• HUME AN, BUTTGEREIT J, AL-SUWAIDI SS, AL-AWADHI AM, JOHN A, BADER M, SEABRA MC, AL-GAZALI L, ALI BR., 2009. Defective cellular trafficking of missense NPR-B mutants underlies Acromesomelic Dysplasia type Maroteaux. Hum Mol Genet.. 18, 267-77
• HUME, ALISTAIR N, WILSON, MIRANDA S, USHAKOV, DMITRY S, FERENCZI, MICHAEL A and SEABRA, MIGUEL C, 2011. Semi-automated analysis of organelle movement and membrane content: understanding Rab-motor complex transport function. Traffic (Copenhagen, Denmark).

• View all publications

Current Research

Cells are fundamental units of the body and their correct function is vital for our health and survival. My research focuses on understanding how cells organise the complex array of internal structures (organelles) whose activities are vital for their function and how defects in these processes cause disease. In particular I am interested in the mechanism by which organelles are transported within the cell and the role played by motor proteins, that move organelles along intracellular protein tracks known as the cytoskeleton, and molecular switches (Rab proteins) that recruit motors to organelles. To address these issues I use melanosomes in skin melanocytes as a model. Several characteristics make this an ideal system for the study of intracellular transport. Firstly melanosomes are large highly motile organelles easily visible by bright-field microscopy. Secondly melanocytes are large, flat, adherent cells that are easily derived and maintained, and transfectable with plasmids and siRNA. Finally a large number of immortal mouse melanocyte cell lines are available that differ in melanosome colour, size and motility. Current interests include: The identification of molecular motors regulating melanosome transport. Understanding Rab signalling pathways that co-ordinate organelle biogenesis and transport. The development of Rab inhibitors.

The contribution of receptor trafficking defects in disease.

• SINGH RK, LIAO W, TRACEY-WHITE D, RECCHI C, TOLMACHOVA T, RANKIN SM, HUME AN and SEABRA MC, 2012. Rab27a Mediated Protease Release Regulates Neutrophil Recruitment By Allowing Uropod Detachment. Journal Of Cell Science. (In Press.)
• TARAFDER, ABUL K, WASMEIER, CHRISTINA, FIGUEIREDO, ANA C, BOOTH, ANTONIA E G, ORIHARA, ASUMI, RAMALHO, JOSE S, HUME, ALISTAIR N and SEABRA, MIGUEL C, 2011. Rab27a targeting to melanosomes requires nucleotide exchange but not effector binding. Traffic (Copenhagen, Denmark). 12(8), 1056-66
• CHIANG, LILIAN, NGO, JULIE, SCHECHTER, JOEL E, KARVAR, SERHAN, TOLMACHOVA, TANYA, SEABRA, MIGUEL C, HUME, ALISTAIR N and HAMM-ALVAREZ, SARAH F, 2011. Rab27b regulates exocytosis of secretory vesicles in acinar epithelial cells from the lacrimal gland. American journal of physiology. Cell physiology. 301(2), C507-21
• HUME, ALISTAIR N, WILSON, MIRANDA S, USHAKOV, DMITRY S, FERENCZI, MICHAEL A and SEABRA, MIGUEL C, 2011. Semi-automated analysis of organelle movement and membrane content: understanding Rab-motor complex transport function. Traffic (Copenhagen, Denmark).
• BOLASCO, GIULIA, TRACEY-WHITE, DHANI C, TOLMACHOVA, TANYA, THORLEY, ANDREW J, TETLEY, TERESA D, SEABRA, MIGUEL C and HUME, ALISTAIR N, 2011. Loss of Rab27 function results in abnormal lung epithelium structure in mice. American journal of physiology. Cell physiology. 300(3), C466-76
• HENDRIX A and HUME AN, 2011. Exosome Signaling In Mammary Gland Development And Cancer. The International Journal Of Developmental Biology. 55(7-9), 879-87
• HUME, AN and SEABRA, MC, 2011. Melanosomes On The Move: A Model To Understand Organelle Dynamics Biochemical Society Transactions. 39, 1191-1196
• ALI BR, NOUVEL I, LEUNG KF, HUME AN, SEABRA MC., 2010. A novel statin-mediated "prenylation block-and-release" assay provides insight into the membrane targeting mechanisms of small GTPases. Biochem Biophys Res Commun. 397, 34-41
• OSTROWSKI M, CARMO NB, KRUMEICH S, RAPOSO G, SAVINA A, MOITA CF, FREITAS RP, SCHAUER K, GOUD B, BENAROCHE P, HUME AN, SEABRA MC, HACOHEN N, AMIGORENA S, MOITA LF, THERY, C, 2010. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 12, 19-30
• RAMALHO JS, LOPES VS, TARAFDER AK, SEABRA MC, HUME AN, 2009. Myosin and Rab linking protein, Myrip, activates MyoVa and MyoVIIa via distinct domains in melanosome transport. Pigment Cell Melanoma Res.. 22, 461-73
• HUME AN, BUTTGEREIT J, AL-SUWAIDI SS, AL-AWADHI AM, JOHN A, BADER M, SEABRA MC, AL-GAZALI L, ALI BR., 2009. Defective cellular trafficking of missense NPR-B mutants underlies Acromesomelic Dysplasia type Maroteaux. Hum Mol Genet.. 18, 267-77
• NIGHTINGALE TD, PATTNI K, HUME AN, SEABRA MC, CUTLER DF., 2009. Rab27a and Myrip regulate the amount and multimeric state of vWF released from endothelial cells. Blood. 113, 5010-8
• WASMEIER C, HUME AN, BOLASCO G, SEABRA MC., 2008. Melanosomes at a glance. J Cell Sci.. 121, 3995-9
• HUME, AN, USHAKOV, DS, TARAFDER, AK, FERENCZI, MA and SEABRA, MC, 2007. Rab27a And Myova Are The Primary Miph Interactors Regulating Melanosome Transport In Melanocytes Journal Of Cell Science. 120(17), 3111-3122
• HUME AN, TARAFDER AK, RAMALHO JS, SVIDERSKAYA EV, SEABRA MC., 2006. A coiled-coil domain of melanophilin is essential for Myosin Va recruitment and melanosome transport in melanocytes. Mol Biol Cell.. 17, 4720-35
• ONFELT B, NEDVETZKI S, BENNINGER RK, PURBHOO MA, SOWINSKI S, HUME AN, SEABRA MC, NEIL MA, FRENCH PM, DAVIS DM, 2006. Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. J Immunol.. 177, 8476-83
• HANNAH MJ, HUME AN, ARRIBAS M, WILLIAMS R, HEWLETT LJ, SEABRA MC, CUTLER DF., 2003. Weibel-Palade bodies recruit Rab27 by a content-driven, maturation-dependent mechanism that is independent of cell type. J Cell Sci.. 116, 3939-48
• GOMES AQ, ALI BR, RAMALHO JS, GODFREY RF, BARRAL DC, HUME AN, SEABRA MC., 2003. Membrane targeting of Rab GTPases is influenced by the prenylation motif. Mol Biol Cell.. 14, 1882-99
• LARIJANI B, HUME AN, TARAFDER AK, SEABRA MC., 2003. Multiple factors contribute to inefficient prenylation of Rab27a in Rab prenylation diseases. J Biol Chem.. 278, 46798-804
• STROM M, HUME AN, TARAFDER AK, BARKAGIANNI E, SEABRA MC., 2002. A family of Rab27-binding proteins. Melanophilin links Rab27a and myosin Va function in melanosome transport. J Biol Chem.. 277, 25423-30
• HUME AN, COLLINSON LM, HOPKINS CR, STROM M, BARRAL DC, BOSSI G, GRIFFITHS GM, SEABRA MC., 2002. The leaden gene product is required with Rab27a to recruit myosin Va to melanosomes in melanocytes Traffic. 3, 193-202
• BARRAL DC, RAMALHO JS, ANDERS R, HUME AN, KNAPTON HJ, TOLMACHOVA T, COLLINSON LM, GOULDING D, AUTHI KS, SEABRA MC., 2002. Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome J Clin Invest.. 110, 247-57
• SEABRA MC, MULES EH, HUME AN., 2002. Rab GTPases, intracellular traffic and disease Trends Mol Med.. 8, 23-30
• PEREIRA-LEAL JB, HUME AN, SEABRA MC., 2001. Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease. FEBS Lett.. 498, 197-200
• RAMALHO JS, TOLMACHOVA T, HUME AN, MCGUIGAN A, GREGORY-EVANS CY, HUXLEY C, SEABRA MC., 2001. Chromosomal mapping, gene structure and characterization of the human and murine RAB27B gene. BMC Genet.. 2, 2
• STINCHCOMBE JC, BARRAL DC, MULES EH, BOOTH S, HUME AN, MACHESKY LM, SEABRA MC, GRIFFITHS GM., 2001. Rab27a is required for regulated secretion in cytotoxic T lymphocytes. J Cell Biol.. 152, 825-34
• HUME AN, COLLINSON LM, RAPAK A, GOMES AQ, HOPKINS CR, SEABRA MC., 2001. Rab27a regulates the peripheral distribution of melanosomes in melanocytes. J Cell Biol.. 152, 795-808