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Prof Parmjit Jat

  • Telephone:

    020 7837 3973

  • Extension:

    020 7878 4099

  • Fax:

    020 7676 2180

  • Email:

    p.jat@ucl.ac.uk

  • Webpage:

    http://www.ion.ucl.ac.uk/

  • Address:

    Department of Neurodegenerative Disease, UCL Institute of Ne,
    Queen Square,
    London,
    WC1N 3BG

  • Appointments:

    Professor of Neurodegenerative Disease, Neurodegenerative Diseases, Institute of Neurology
No image is available

Research Summary

Normal somatic cells undergo a finite number of divisions and then cease dividing whereas cancer cells are able to proliferate indefinitely. This irreversible program of cell cycle arrest is triggered in response to a variety of intrinsic and extrinsic stimuli including alteration in telomere length and structure, DNA damage, physiological stresses and activation of certain oncogenes. It can lead to removal of defective and potentially cancerous cells from the proliferating pool thereby preventing neoplastic transformation and tumour development. It can also compromise tissue repair and regeneration and contribute to organismal ageing. The acquisition of an infinite proliferative potential is one of the six key events that are required for neoplastic transformation and one of the least understood since the underlying mechanism that controls cellular senescence and the signal transduction pathways involved are poorly understood. My research is aimed at identifying the underlying molecular basis for the finite proliferative life span and then if and how the key components are abrogated in cancer cells. We also aim to determine if these key components are conserved across species and in different cell types. Such components should represent novel, important and direct targets for both cancer and anti-ageing therapies.

Research Activities

  • Cellular mechanisms underlying neurodegeneration
  • Identification of new components in Parkinson's Disease signalling pathways

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. Caballero OL,Cohen T,Gurung S,Chua R,Lee P,Chen YT,Jat P,Simpson AJ (2013) Effects of CT-Xp Gene Knock down in Melanoma Cell Lines. Oncotarget, 4(4), 531 - 541.
  2. Gorvin CM,Wilmer MJ,Piret SE,Harding B,van den Heuvel LP,Wrong O,Jat PS,Lippiat JD,Levtchenko EN,Thakker RV (2013) Receptor-mediated endocytosis and endosomal acidification is impaired in proximal tubule epithelial cells of Dent disease patients. Proc Natl Acad Sci U S A, 110(17), 7014 - 7019. 10.1073/pnas.1302063110.
  3. Guhr SS,Sachs M,Wegner A,Becker JU,Meyer TN,Kietzmann L,Schlossarek S,Carrier L,Braig M,Jat PS,Stahl RA,Meyer-Schwesinger C (2013) The expression of podocyte-specific proteins in parietal epithelial cells is regulated by protein degradation. Kidney Int. 10.1038/ki.2013.115.
  4. Rovillain E,Mansfield L,Caetano C,Alvarez-Fernandez M,Caballero OL,Medema RH,Hummerich H,Jat PS (2011) Activation of nuclear factor-kappa B signalling promotes cellular senescence. Oncogene, 30(20), 2356 - 2366. 10.1038/onc.2010.611.
  5. Vaughan S,Jat PS (2011) Deciphering the role of nuclear factor-κB in cellular senescence. Aging (Albany NY), 3(10), 913 - 919.
  6. Rovillain E,Mansfield L,Lord CJ,Ashworth A,Jat PS (2011) An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence. BMC Genomics, 12, 355. 10.1186/1471-2164-12-355.
  7. Goold R,Rabbanian S,Sutton L,Andre R,Arora P,Moonga J,Clarke AR,Schiavo G,Jat P,Collinge J,Tabrizi SJ (2011) Rapid cell-surface prion protein conversion revealed using a novel cell system NAT COMMUN, 2. 10.1038/ncomms1282.
  8. Jia M,Souchelnytskyi N,Hellman U,O'Hare M,Jat PS,Souchelnytskyi S (2010) Proteome profiling of immortalization-to-senescence transition of human breast epithelial cells identified MAP2K3 as a senescence-promoting protein which is downregulated in human breast cancer PROTEOM CLIN APPL, 4(10-11), 816 - 828. 10.1002/prca.201000006.
  9. Sakairi T,Abe Y,Jat PS,Kopp JB (2010) Cell-cell contact regulates gene expression in CDK4-transformed mouse podocytes. Am J Physiol Renal Physiol, 299(4), F802 - F809. 10.1152/ajprenal.00205.2010.
  10. Sakairi T,Abe Y,Kajiyama H,Bartlett LD,Howard LV,Jat PS,Kopp JB (2010) Conditionally immortalized human podocyte cell lines established from urine. Am J Physiol Renal Physiol, 298(3), F557 - F567. 10.1152/ajprenal.00509.2009.
  11. Alexopoulou AN,Leao M,Caballero OL,Da Silva L,Reid L,Lakhani SR,Simpson AJ,Marshall JF,Neville AM,Jat PS (2010) Dissecting the transcriptional networks underlying breast cancer: NR4A1 reduces the migration of normal and breast cancer cell lines. Breast Cancer Res, 12(4), R51. 10.1186/bcr2610.
  12. Wood-Kaczmar A,Gandhi S,Yao Z,Abramov AY,Miljan EA,Keen G,Stanyer L,Hargreaves I,Klupsch K,Downward J,Mansfield L,Jat P,Taylor J,Heales S,Duchen MR,Latchman D,Tabrizi SJ,Wood NW (2009) PINK1 is necessary for long term survival and mitochondrial function in primary human dopaminergic neurons JOURNAL OF NEUROCHEMISTRY, 109, 301 - 302.
  13. Grigoriadis A,Oliver GR,Tanney A,Kendrick H,Smalley MJ,Jat P,Neville AM (2009) Identification of differentially expressed sense and antisense transcript pairs in breast epithelial tissues. BMC Genomics, 10, 324. 10.1186/1471-2164-10-324.
  14. Docquier F,Kita GX,Farrar D,Jat P,O'Hare M,Chernukhin I,Gretton S,Mandal A,Alldridge L,Klenova E (2009) Decreased poly(ADP-ribosyl)ation of CTCF, a transcription factor, is associated with breast cancer phenotype and cell proliferation. Clin Cancer Res, 15(18), 5762 - 5771. 10.1158/1078-0432.CCR-09-0329.
  15. Hein J,Boichuk S,Wu J,Cheng Y,Freire R,Jat PS,Roberts TM,Gjoerup OV (2009) Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol, 83(1), 117 - 127. 10.1128/JVI.01515-08.
  16. Jefferies HB,Cooke FT,Jat P,Boucheron C,Koizumi T,Hayakawa M,Kaizawa H,Ohishi T,Workman P,Waterfield MD,Parker PJ (2008) A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding. EMBO Rep, 9(2), 164 - 170. 10.1038/sj.embor.7401155.
  17. Wood-Kaczmar A,Gandhi S,Yao Z,Abramov AY,Miljan EA,Keen G,Stanyer L,Hargreaves I,Klupsch K,Deas E,Downward J,Mansfield L,Jat P,Taylor J,Heales S,Duchen MR,Latchman D,Tabrizi SJ,Wood NW (2008) PINK1 is necessary for long term survival and mitochondrial function in human dopaminergic neurons. PLoS One, 3(6), e2455. 10.1371/journal.pone.0002455.
  18. Yagüe E,Arance A,Kubitza L,O'Hare M,Jat P,Ogilvie CM,Hart IR,Higgins CF,Raguz S (2007) Ability to acquire drug resistance arises early during the tumorigenesis process. Cancer Res, 67(3), 1130 - 1137. 10.1158/0008-5472.CAN-06-2574.
  19. Lock RL,Szeto TH,Entwistle A,Gjoerup OV,Jat PS (2007) Preparation of monoclonal antibodies against the spindle checkpoint kinase Bub1. Hybridoma (Larchmt), 26(3), 140 - 147. 10.1089/hyb.2007.003.
  20. Jat P (2007) MAbs 2B8, 13G9, and 17E9 against mouse Bub1 protein HYBRIDOMA, 26(3), 190 - 190. 10.1089/hyb.2007.9982.
  21. Gjoerup OV,Wu J,Chandler-Militello D,Williams GL,Zhao J,Schaffhausen B,Jat PS,Roberts TM (2007) Surveillance mechanism linking Bub1 loss to the p53 pathway. Proc Natl Acad Sci U S A, 104(20), 8334 - 8339. 10.1073/pnas.0703164104.
  22. Jia M,Souchelnytskyi N,Hellman U,Jat P,O'Hare MJ,Souchelnytskyi S (2006) Proteome profiling of conditionally immortalized human breast epithelial cells MOL CELL PROTEOMICS, 5(10), S267 - S267.
  23. Wood-Kaczmar A,Gandhi S,Jat P,Miljan EA,Sinden J,Keen GJ,Taylor J,Latchman DS,Wood NW,Tabrizi SJ (2006) Generation of a cellular model of PINK1 parkinsonism in primary human dopaminergic neurons MOVEMENT DISORDERS, 21, S546 - S546.
  24. Gandhi S,Wood-Kaczmar A,Jat P,Latchman DS,Tabrizi SJ,Wood NW (2006) Investigation of PINK1 dysfunction in Parkinson's disease MOVEMENT DISORDERS, 21, S546 - S547.
  25. Lopez-Garcia J,Periyasamy M,Thomas RS,Christian M,Leao M,Jat P,Kindle KB,Heery DM,Parker MG,Buluwela L,Kamalati T,Ali S (2006) ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases. Nucleic Acids Res, 34(21), 6126 - 6136. 10.1093/nar/gkl875.
  26. Grønning LM,Tingsabadh R,Hardy K,Dalen KT,Jat PS,Gnudi L,Shepherd PR (2006) Glucose induces increases in levels of the transcriptional repressor Id2 via the hexosamine pathway. Am J Physiol Endocrinol Metab, 290(4), E599 - E606. 10.1152/ajpendo.00242.2005.
  27. Kawata S,Suzuki J,Maruoka M,Mizutamari M,Ishida-Kitagawa N,Yogo K,Jat PS,Shishido T (2006) Retrovirus-mediated conditional immortalization and analysis of established cell lines of osteoclast precursor cells. Biochem Biophys Res Commun, 350(1), 97 - 104. 10.1016/j.bbrc.2006.09.020.
  28. Grigoriadis A,MacKay A,Reis-Filho JS,Steele D,Iseli C,Stevenson BJ,Jongeneel CV,Valgeirsson H,Fenwick K,Iravani M,Leao M,Simpson AJG,Strausberg RL,Jat PS,Ashworth A,Neville AM,O'Hare MJ (2006) Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data Breast Cancer Research, 8(5), R56. 10.1186/bcr1604.
  29. Hardy K,Mansfield L,MacKay A,Benvenuti S,Ismail S,Arora P,O'Hare MJ,Jat PS (2005) Transcriptional networks and cellular senescence in human mammary fibroblasts Molecular Biology of the Cell, 16(2), 943 - 953.
  30. Lock RL,Benvenuti S,Jat PS (2004) Immortalisation by SV40 large T antigen., 467. 10.1002/0471656437.
  31. Fauth C,O'Hare MJ,Lederer G,Jat PS,Speicher MR (2004) Order of genetic events is critical determinant of aberrations in chromosome count and structure Genes, Chromosomes and Cancer, 40(4), 298 - 306.
  32. Tarunina M,Alger L,Chu G,Munger K,Gudkov A,Jat PS (2004) Functional genetic screen for genes involved in senescence: role of Tid1, a homologue of the Drosophila tumor suppressor l(2)tid, in senescence and cell survival. Molecular and Cellular Biology, 24(24), 10792 - 10801. 10.1128/MCB.24.24.10792-10801.2004.
  33. Suzuki J,Sukezane T,Akagi T,Georgescu MM,Ohtani M,Inoue H,Jat PS,Goff SP,Hanafusa H,Shishido T (2004) Loss of c-abl facilitates anchorage-independent growth of p53- and RB- deficient primary mouse embryonic fibroblasts. Oncogene, 23(52), 8527 - 8534. 10.1038/sj.onc.1207894.
  34. Cotsiki M,Lock RL,Cheng Y,Williams GL,Zhao J,Perera D,Freire R,Entwistle A,Golemis EA,Roberts TM,Jat PS,Gjoerup OV (2004) Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1 Proceedings of the National Academy of Sciences of the United States of America, 101(4), 947 - 952. 10.1073/pnas.0308006100.
  35. Mackay A,Jones C,Dexter T,Silva RL,Bulmer K,Jones A,Simpson P,Harris RA,Jat PS,Neville AM,Reis LF,Lakhani SR,O'Hare MJ (2003) cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells. Oncogene, 22(17), 2680 - 2688.
  36. Djelloul S,Tarunina M,Barnouin K,Mackay A,Jat PS (2002) Differential protein expression, DNA binding and interaction with SV40 large tumour antigen implicate the p63-family of proteins in replicative senescence. Oncogene, 21(7), 981 - 989. 10.1038/sj.onc.1205253.
  37. Benvenuti S,Cramer R,Bruce J,Waterfield MD,Jat PS (2002) Identification of novel candidates for replicative senescence by functional proteomics ONCOGENE, 21(28), 4403 - 4413. 10.1038/sj.onc.1205525.
  38. Lidington EA,Rao RM,Marelli-Berg FM,Jat PS,Haskard DO,Mason JC (2002) Conditional immortalization of growth factor-responsive cardiac endothelial cells from H-2K(b)-tsA58 mice AM J PHYSIOL-CELL PH, 282(1), C67 - C74.
  39. Benvenuti S,Cramer R,Quinn CC,Bruce J,Zvelebil MJ,Corless S,Bond J,Yang A,Hockfield S,Burlingame AL,Waterfield MD,Jat PS (2002) Differential proteome analysis of replicative senescence in rat embryo fibroblasts. Molecular and Cellular Proteomics, 1(4), 280 - 292. 10.1074/mcp.M100028-MCP200.
  40. Lidington EA,Rao RM,Marelli-Berg F,Jat P,Haskard DO,Mason JC (2001) Isolation and characterisation of conditionally immortal growth factor responsive cardiac endothelial cells (EC) from H-2K(b)-tsA58 transgenic mice RHEUMATOLOGY, 40, 8 - 8.
  41. Darmon AJ,Jat PS (2001) Immortalisation of primary rodent cells by SV40, 5, 7 - 41.
  42. O'Hare M,Bond J,Clarke C,Takeuchi Y,Atherton AJ,Berry C,Moody J,Silver ARJ,Davies DC,Alsop AE,Neville AM,Jat PS (2001) Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. Proceedings of the National Academy of Sciences of the United States of America, 98(2), 646 - 651. 10.1073/pnas.98.2.646.
  43. Mason JC,Lidington EA,Rao RM,Marelli-Berg FM,Jat PS,Haskard DO (2001) Use of H-2Kb-tsA58 transgenic mice to generate conditionally immortalized, growth factor responsive mouse cardiac endothelial cells for in vitro studies FASEB J, 15(5), A947 - A947.
  44. Sinden JD,Pilcher HR,Mann VM,Kershaw TR,Dong Z,Rodriguez T,Barnetson A,Majumdar S,Weeratunga N,Price J,Jat PS (2000) Human neural stem cells: A comparison of genetic and epigenetic approaches to long-term culturing EUR J NEUROSCI, 12, 245 - 245.
  45. Darmon AJ,Jat PS (2000) BAP37 and Prohibitin are specifically recognized by an SV40 T antigen antibody. Mol Cell Biol Res Commun, 4(4), 219 - 223. 10.1006/mcbr.2001.0281.
  46. Lidington EA,Rao RM,Marelli-Berg F,Jat P,Haskard DO,Mason JC (2000) Establishment and characterisation of a conditionally transformed immortalised murine cardiac endothelial cell line isolated from H2kb-tsA58 transgenic mice. CIRCULATION, 102(18), 329 - 329.
  47. John HA,Laffling AJ,Marrs J,Baird A,Jat PS,Holdstock NB,Rossdale PD (2000) Establishment and characterization of equine autonomic ganglion cell lines to enable direct testing of candidate toxins involved in equine dysautonomia (grass sickness) Cell Biology and Toxicology, 16(1), 63 - 74.
  48. Powell AJ,Darmon AJ,Gonos ES,Lam EW,Peden KW,Jat PS (1999) Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen Oncogene, 18(51), 7343 - 7350.
  49. Hugnot JP,Jat P,Sinden J (1998) Characterisation of telencephalon E10 cell cultures EUR J NEUROSCI, 10, 8 - 8.
  50. Gonos ES,Derventzi A,Kveiborg M,Agiostratidou G,Kassem M,Clark BFC,Jat PS,Rattan SIS (1998) Cloning and identification of genes that associate with mammalian replicative senescence Experimental Cell Research, 240, 66 - 74.

Qualifications

  • 1982: Doctor of Philosophy, Imperial College of Science, Technology and Medicine
  • 1978: Bachelor of Science, University of Bath

Keywords

  • Brain tumours in adults
  • Cancer cell cycle
  • Cell culture
  • Cell senescence, ageing and cancer
  • Gene expression
  • Gene expression profiling - tissue level
  • Genetic manipulation (including knockout/knockin)
  • Genetic screens
  • Genetically encoded reporters/indicators
  • Genomic analyses
  • Genomics
  • MRNA
  • MiRNA analysis
  • Microarrays
  • Neurodegeneration
  • Neurodegenerative diseases
  • Proliferation
  • Recombinant protein expression
  • Viral vectors