Andrew M Fry

Personal Details

Andrew Fry, FRSBCollege Director of Research
Andrew Fry

Department: Molecular and Cell Biology
College of Life Sciences University
Telephone: 0116 229 7069
Email: amf5@le.ac.uk
Address: Lancaster Rd, LE1 7HB
Web Links:

Qualifications

  • Professor of Cell Biology
  • College Director of Research
  • Fellow of the Royal Society of Biology
  • Fellow of the Higher Education Academy
  • M.A. (Hons) Biochemistry University of Oxford St. Peter’s College
  • D.Phil. Clinical Medicine University of Oxford Wolfson College

Teaching

  • Introductory Courses on Medical Biosciences
  • Molecular Cell Biology, Cell Cycle Control
  • Cancer Cell Biology

Research

We aim to better understand the biology of cancer so that we can develop more effective treatments for patients with this major disease of unmet need.

We take mechanism-based molecular and cell biology approaches to gain new insights into cancer-related processes, including cell division, microtubule organization, mitotic spindle assembly, centrosome biology and cell cycle checkpoints. Much of our research focuses on the regulation of these processes by protein phosphorylation and, more specifically, by members of the human NEK protein kinase family.

We are investigating how perturbation of these normal biological processes leads to the cancer-related phenotypes of aneuploidy, chromosome instability, tumour heterogeneity and metastasis. We wish to identify cellular mechanisms of action, resistance pathways and biomarkers that will enable better use of current microtubule-based chemotherapies and generation of new personalised approaches to cancer treatment.

In addition to our work in cancer biology, we are interested in how inherited genetic defects lead to the multi-organ syndromic diseases known as ciliopathies. These developmental and degenerative disorders, which include cystic kidney diseases and retinopathies, arise through defects in the organization or signaling function of the antenna-like microtubule-based organelle, called the primary cilium.

Supervision

  • NEK kinase protein regulation and function
  • Cell cycle-dependent regulation of microtubule associated proteins
  • Regulation of centrosome organization and number in cancer cells

Publications (Since 2010)

  1. Hayward DG, Newbatt Y, Pickard L, Byrne E, Mao G, Burns S, Sahota NK, Workman P, Collins I, Aherne W and Fry AM (2010) Identification by high-throughput screening of viridin analogs as biochemical and cell-based inhibitors of the cell cycle-regulated Nek2 kinase. Journal of Biomolecular Screening 15, 918-927. [Journal Cover Image]
  2. Mardin B, Lange C, Baxter JE, Hardy T, Scholz SR, Fry AM and Schiebel E (2010) Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nature Cell Biology 12, 1166-1176.
  3. Lopes CAM, Prosser S, Romio L, Merdes A, Hirst R, O’Callaghan C, Woolf A and Fry AM (2011) Centriolar satellites are assembly points for proteins implicated in human ciliopathies, including oral-facial-digital syndrome 1. Journal of Cell Science 124, 600- 612.
  4. Alexander J, Lim D, Joughin BA, Hegemann B, Hutchins JR, Ehrenberger T, Ivins F, Sessa F, Hudecz O, Nigg EA, Fry AM, Musacchio A, Stukenberg PT, Mechtler K, Peters J-M, Smerdon SJ and Yaffe MB (2011) Phosphorylation motifs of major mitotic kinases reveal sequence and spatial exclusivity as a basis for context-dependent mitotic signaling. Science Signaling 4: ra42
  5. Croasdale R, Ivins FJ, Muskett F, Daviter T, Scott DJ, Hardy T, Smerdon SJ, *Fry AM and *Pfuhl M (2011) An undecided coiled-coil: the leucine zipper of Nek2 exhibits atypical conformational exchange dynamics. Journal of Biological Chemistry 286, 27537- 27547. *Joint corresponding authors
  6. Zalli D, Bayliss R and Fry AM (2012) The Nek8 protein kinase Nek8, mutated in the human cystic kidney disease nephronophthisis, is both activated and degraded during ciliogenesis. Human Molecular Genetics 21, 1155-1171.
  7. Innocenti P, Cheung K-WJ, Solanki S, Mas-Droux C, Rowan F, Yeoh S, Boxall K, Westlake M, Pickard L, Hardy T, Baxter JE, Aherne GW, Bayliss R, Fry AM and Hoelder S. (2012) Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: SAR, structural biology and cellular activity. Journal of Medicinal Chemistry 55, 3228-3241.
  8. Prosser SL, Samant MD, Morrison CE, Baxter JE and Fry AM (2012) Oscillation of APC/C activity during cell cycle arrest drives centrosome amplification. Journal of Cell Science 125, 5353-5368.
  9. Venoux M, Tait X, Hames RS Straatman KR, Woodland HR and Fry AM (2013) Poc1A and Poc1B act together in human cells to ensure centriole integrity. Journal of Cell Science 126, 163-175.
  10. Richards MW, Law EWP, Rennalls LP, Busacca S, O’Regan L, Straube A, Fry AM, Fennell DA, and Bayliss R (2014) Crystal structure of EML1 reveals the basis for Hsp90-dependence of oncogenic EML4-ALK by disruption of an atypical b-propeller domain. Proc. Natl. Acad. Sci. (U.S.A.) 111, 5195-5200.
  11. Hardy T, Lee M, Hames RS, Prosser SL, Cheary D-M, Samant MD, Schultz F, Baxter JE, Rhee K and Fry AM (2014) Multisite phosphorylation of C-Nap1 releases it from Cep135 to trigger centrosome disjunction. Journal of Cell Science 127, 2493-506.
  12. Jamaladdin S, Kelly RDW, O’Regan L, Dovey OM, Hodson G, Millard C, Fry AM, Schwabe J and Cowley S (2014) Histone deacetylases (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells. Proc. Natl. Acad. Sci. (U.S.A.) 111, 9840-9845.
  13. Thauvin-Robinet C, Lee JS, Lopez E, Herranz-Perez V, Franco B, Jego L, Shida T, Ye F, Pasquier L, Loget P, Gigot N, Aral B, Lopes CAM, Thevenon J, Munnich A, Vekemans M, Huet F, Fry AM, Saunier S, Riviere JB, Attie-Bitach T, Garcia-Verdugo JM, Faivre L, Megarbane A and Nachury MV (2014) The oral-facial-digital syndrome gene C2CD3 is a positive regulator of centriole elongation. Nature Genetics 46, 905-911
  14. Neal CP, Fry AM, Moreman C, McGregor A, Garcea G, Berry DP and Manson MM (2014) Overexpression of the Nek2 kinase in colorectal cancer correlates with beta-catenin relocalization and shortened cancer-specific survival. Journal of Surgical Oncology 110, 828-838.
  15. Beck BB, Phillips JB, Bartram MP, Wegner J, Thoenes M, Pannes A, Sampson J, Heller R, Göbel H, Koerber F, Neugebauer A, Hedergott A, Nürnberg G, Nürnberg P, Thiele H, Altmüller J, Toliat, M.R., Staubach S, Boycott KM, Valente EM, Janecke AR, Eisenberger T, Bergmann C, Tebbe L, Wang Y, Wu Y, Fry AM, Westerfield M, Wolfrum U and Bolz HJ (2014) Mutation of POC1B in severe syndromic retinal ciliopathy. Human Mutation 35, 1153-1162.
  16. Jerman S, Ward HH, Lee R, Lopes CAM, Fry AM, MacDougall M and Wandinger-Ness A (2014) OFD1 and flotillins are integral components of a ciliary signaling protein complex organized by polycystins in renal epithelia and odontoblasts. PLoS ONE 9: e106330.
  17. Patel JT, Bottrill A, Prosser S, Jayaraman S, Straatman KR, Fry AM and Shackleton S (2014) Mitotic phosphorylation of SUN1 loosens its connection with the nuclear lamina whilst the LINC complex remains intact. Nucleus 5, 462-473.
  18. Richards MW, O’Regan L, Roth D, Montgomery JM, Straube A, *Fry AM and *Bayliss R (2015) Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein requires an N-terminal trimerization domain. Biochemical Journal 467, 529-536. *Joint corresponding authors.
  19. O’Regan L, Sampson J, Richards MW, Knebel A, Roth D, Hood FE, Straube A, Royle SJ, Bayliss R and Fry AM (2015) Hsp72 is targeted to the mitotic spindle by Nek6 kinase to promote K-fibre assembly and mitotic progression. Journal of Cell Biology 209, 349-358. [Article highlighted In This Issue].
  20. Prosser SL, Sahota NK, Pelletier L, Morrison CG and Fry AM (2015) Nek5 promotes centrosome integrity in interphase and loss of centrosome cohesion in mitosis. Journal of Cell Biology 209, 339-348
  21. Rogerson DT, Sachdeva A, Wang K, Haq T, Kazlauskaite A, Hancock SM, Huguenin- Dezot N, Muqit MMK, Fry AM, Bayliss R and Chin JW (2015) Efficient genetic encoding of phosphoserine and its nonhydrolyzable analog. Nature Chemical Biology 11, 496-503.
  22. Sabir SR, Sahota NK, Jones GDD and Fry AM (2015) Loss of Nek11 prevents G2/M arrest and promotes cell death in HCT116 colorectal cancer cells exposed to therapeutic DNA damaging agents. PLoS ONE 10, e0140975.
  23. Haq T, Richards MW, Burgess SG, Gallego P, Yeoh S, O’Regan L, Reverter D, Roig J, Fry AM and Bayliss R (2015) Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization. Nature Communications 6, 8771.
  24. Coxon CR, Wong C, Bayliss R, Boxall K, Carr KH, Fry AM, Hardcastle IR, Matheson CJ, Newell DR, Sivaprakasam M, Thomas H, Yoeh S, Wang LZ, Griffin RJ, Golding BT and Cano C (2016) Structure-guided design of purine-based probes for selective Nek2 inhibition. Oncotarget 13249.
  25. Mitcheson DF, Bottrill A, Carr K, Coxon, CR, Cano, C, Golding BT, Griffin RJ, Fry AM, Doerig C, Bayliss R, Tobin A (2016) A new tool for chemical genetic investigation of Plasmodium falciparum PfNek-2 NIMA-related kinase. Malaria J. 15, 535.
  26. Sampson J, O’Regan L, Dyer MJD, Bayliss R and Fry AM (2017) Hsp72 and Nek6 cooperate to cluster amplified centrosomes in cancer cells. Cancer Research 77, 4785-4796.

Share this page:

Contact Details

Department of Molecular and Cell Biology

T: +44(0)116 229 7038
E: MolCellBiol@le.ac.uk

Map with link to google maps geotag of Henry Wellcome

Henry Wellcome Building - University of Leicester, Lancaster Rd, LE1 7HB

Postal: Henry Wellcome Building, University of Leicester, Leicester, LE1 7RH

Directions on Arrival to The Henry Wellcome Building

Student complaints procedure

Accessibility

DisabledGo logo

The University of Leicester is committed to equal access to our facilities. DisabledGo has a detailed accessibility guide for the Henry Wellcome Building.