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Ketan J. Patel

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Ketan J. Patel
FRS FMedSci MRCP
Patel in 2015
Born
Ketan Jayakrishna Patel

Nairobi, Kenya[5]
Nationality
EducationBanda School
Marlborough College
Alma mater
AwardsEMBO Member
Scientific career
Fields
Institutions
ThesisAntigen presentation by the B cell antigen receptor (1994)
Doctoral advisorMichael Neuberger[3][4]
Website

www2.mrc-lmb.cam.ac.uk/group-leaders/n-to-s/kj-patel/

Ketan Jayakrishna Patel[5] is a British–Kenyan scientist who is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford.[7] Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).[8][9][10][11][12]

Education and early life

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Patel is of Gujarati Indian origin and was born in Nairobi, Kenya. His early education took place in his home country at Hospital Hill Primary School and Banda Preparatory School. In 1976, Patel left Kenya to continue his secondary education at Marlborough College in Wiltshire.[5] He subsequently went to medical school at the Royal Free Hospital and the University of London (1980–1985) where he qualified as a doctor with distinctions in Medicine and Surgery.

Patel originally trained as a gastroenterologist but also was awarded an MRC training fellowship to work with Michael Neuberger[3] FRS at the MRC Laboratory of Molecular Biology (1989–1993). He completed a PhD in which he conducted research to understand the role the membrane bound form of the antibody molecule.[13]

Career and Research

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After his PhD, Patel was awarded an MRC Clinician Scientist Fellowship and started working with A. Venkitaraman (1995–1998) where he contributed to the discovery that the BRCA2 protein functions in repairing damaged DNA.[11] Patel eventually joined the LMB as a tenure track group leader (1999–2007) and was later on promoted to tenured principal investigator at the LMB (2007–2020). He was appointed professor of Molecular Medicine and Stem Cell Genomics in 2017.[14] He also served on the Life Sciences jury for the Infosys Prize in 2018 and 2019.

In 2020 Patel was appointed as Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford.[15]

Patel's research is mainly concerned with how living cells repair DNA crosslinks. These lesions cause the two opposing strands of DNA to be covalently bound together. Such crosslinks are lethal to cells since they would prevent DNA from being copied (DNA replication) or for the genes it carries to be read (DNA transcription). DNA crosslinks are caused by numerous anti-cancer drugs (such as cisplatin), but they also must arise naturally since individuals carrying a genetic defect in crosslink repair suffer from the illness Fanconi anaemia. This devastating inherited illness leads to congenital defects, progressive loss of blood production and an enormous lifetime risk of certain cancers.

Patel's research on the Fanconi pathway has provided key molecular insights into how cells remove DNA crosslinks[1][2] and, most recently, his lab discovered that reactive aldehydes are the likely natural agents that produce them.[16][17][18][19] Aldehydes are ubiquitous metabolites, arising not only from many metabolic pathways but also when cells process alcohol. His lab showed that mammals use a two-tier protection mechanism to counteract aldehydes, consisting of (1) enzymatic clearance of aldehydes by aldehyde dehydrogenases and (2) the Fanconi DNA repair pathway (see Figure). Although Fanconi anaemia is a very rare condition, genetic deficiency of this two-tier protection mechanism is actually very common in man: up to 500 million Asians are deficient in first tier protection due to mutations in the gene ALDH2.

Two-tier protection against reactive aldehydes

Awards and honours

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Patel was elected to Research Fellow of Gonville and Caius College, Cambridge (1996–2000). He was also awarded the Max Perutz Prize for his PhD research at the LMB (1994), a prize from the Children with Cancer Research Fund for breakthroughs into the causes of childhood leukaemia (2005) and the Award of Merit from the Fanconi Anemia Research Fund. In 2013, Patel was elected EMBO Membership and a Fellow of the Academy of Medical Sciences (FMedSci).[20] In 2015, he was elected fellow of the Royal Society of London (FRS). His certificate for election to Fellow of the Royal Society (FRS) in 2015[21] reads:

KJ Patel has made seminal discoveries on the Fanconi pathway of DNA repair. Deficiencies in this pathway lead to defective development, stem cell attrition and cancer in humans. Patel has unveiled the primary role of the Fanconi pathway in resolving DNA damage caused by aldehydes (whether generated by endogenous metabolism or though oxidation of ingested substances such as ethanol). He has also advanced our knowledge of the molecular mechanism of action of the pathway and thrown light on its roles in preserving blood stem cells as well as in protection from cancer.[22]

Patel derived the most pleasure when he received was a lifetime achievement award from the Fanconi Anemia research fund – a charity set up by the families of those effected by this devastating illness.

References

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  1. ^ a b Joenje, H; Patel, K. J. (2001). "The emerging genetic and molecular basis of Fanconi anaemia". Nature Reviews Genetics. 2 (6): 446–57. doi:10.1038/35076590. PMID 11389461. S2CID 14130453.
  2. ^ a b Niedzwiedz, W; Mosedale, G; Johnson, M; Ong, C. Y.; Pace, P; Patel, K. J. (2004). "The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair". Molecular Cell. 15 (4): 607–20. doi:10.1016/j.molcel.2004.08.009. PMID 15327776.
  3. ^ a b Patel, K.J.; Neuberger, M.S. (1993). "Antigen presentation by the B cell antigen receptor is driven by the αβ sheath and occurs independently of its cytoplasmic tyrosines". Cell. 74 (5): 939–946. doi:10.1016/0092-8674(93)90473-4. ISSN 0092-8674. PMID 8374958. S2CID 140208777.
  4. ^ Ketan J. Patel (1 December 2013). "Michael Neuberger obituary: Biochemist who discovered how antibodies are greatly improved". The Guardian. Archived from the original on 27 March 2015.
  5. ^ a b c "PATEL, Dr Ketan Jayakrishna". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  6. ^ "Ketan J. Patel CV". University of Cambridge. Archived from the original on 21 July 2013.
  7. ^ "MRC Molecular Haematology Unit appoints new Director". Medical Research Council. 1 April 2020. Archived from the original on 23 September 2020. Retrieved 14 November 2020.
  8. ^ Pace, P; Mosedale, G; Hodskinson, M. R.; Rosado, I. V.; Sivasubramaniam, M; Patel, K. J. (2010). "Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway". Science. 329 (5988): 219–23. Bibcode:2010Sci...329..219P. doi:10.1126/science.1192277. PMID 20538911. S2CID 206527645.
  9. ^ Crossan, G. P.; Van Der Weyden, L; Rosado, I. V.; Langevin, F; Gaillard, P. H.; McIntyre, R. E.; Sanger Mouse Genetics, Project; Gallagher, F; Kettunen, M. I.; Lewis, D. Y.; Brindle, K; Arends, M. J.; Adams, D. J.; Patel, K. J. (2011). "Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia". Nature Genetics. 43 (2): 147–52. doi:10.1038/ng.752. PMC 3624090. PMID 21240276. Open access icon
  10. ^ Joenje, H (2011). "Metabolism: Alcohol, DNA and disease". Nature. 475 (7354): 45–6. doi:10.1038/475045a. PMID 21734701.
  11. ^ a b Patel, K. J.; Yu, V. P.; Lee, H; Corcoran, A; Thistlethwaite, F. C.; Evans, M. J.; Colledge, W. H.; Friedman, L. S.; Ponder, B. A.; Venkitaraman, A. R. (1998). "Involvement of Brca2 in DNA repair". Molecular Cell. 1 (3): 347–57. doi:10.1016/s1097-2765(00)80035-0. PMID 9660919.
  12. ^ Carpten, J. D.; Faber, A. L.; Horn, C; Donoho, G. P.; Briggs, S. L.; Robbins, C. M.; Hostetter, G; Boguslawski, S; Moses, T. Y.; Savage, S; Uhlik, M; Lin, A; Du, J; Qian, Y. W.; Zeckner, D. J.; Tucker-Kellogg, G; Touchman, J; Patel, K; Mousses, S; Bittner, M; Schevitz, R; Lai, M. H.; Blanchard, K. L.; Thomas, J. E. (2007). "A transforming mutation in the pleckstrin homology domain of AKT1 in cancer". Nature. 448 (7152): 439–44. Bibcode:2007Natur.448..439C. doi:10.1038/nature05933. PMID 17611497. S2CID 4302164.
  13. ^ Patel, Ketan Jayakrishna (1994). Antigen presentation by the B cell antigen receptor (PhD thesis). University of Cambridge. OCLC 53650905.
  14. ^ "Senior Academic Promotions, 1 October 2017 exercise: Appointments and titles". Cambridge University Reporter. 26 July 2017. Retrieved 17 November 2020.
  15. ^ "MRC Molecular Haematology Unit appoints new Director". Medical Research Council. 1 April 2020. Archived from the original on 23 September 2020. Retrieved 14 November 2020.
  16. ^ Langevin, Frédéric; Crossan, Gerry P.; Rosado, Ivan V.; Arends, Mark J.; Patel, Ketan J. (2011). "Fancd2 counteracts the toxic effects of naturally produced aldehydes in mice". Nature. 475 (7354): 53–58. doi:10.1038/nature10192. ISSN 0028-0836. PMID 21734703. S2CID 205225420.
  17. ^ Rosado, I. V.; Patel, KJ (2011). "Formaldehyde catabolism is essential in cells deficient for the Fanconi anemia DNA repair pathway". Nat Struct Mol Biol. 18 (12): 1432–4. doi:10.1038/nsmb.2173. PMID 22081012. S2CID 27164069.
  18. ^ Garaycoechea, J. I.; Patel, KJ (2012). "Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function". Nature. 489 (7417): 571–575. Bibcode:2012Natur.489..571G. doi:10.1038/nature11368. PMID 22922648. S2CID 4396869.
  19. ^ Pontel, L. B.; Patel, KJ (2015). "Endogenous Formaldehyde Is a Hematopoietic Stem Cell Genotoxin and Metabolic Carcinogen". Mol Cell. 60 (1): 177–188. doi:10.1016/j.molcel.2015.08.020. PMC 4595711. PMID 26412304.
  20. ^ "Dr Ketan Patel FRS FMedSci". London: Academy of Medical Sciences. Archived from the original on 12 May 2015.
  21. ^ "Dr Ketan Patel FRS". London: Royal Society. Archived from the original on 17 November 2015.
  22. ^ "Dr Ketan Patel FMedSci FRS". London: The Royal Society. Archived from the original on 2 May 2015.
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