Ketan J. Patel

Last updated

KJ Patel

FRS FMedSci MRCP
Ketan Jayakrishna Patel FRS.jpg
Ketan Patel in 2015, portrait from the Royal Society
Born
Ketan Jayakrishna Patel

Nairobi, Kenya [1]
Nationality
EducationBanda School
Marlborough College
Alma mater
Awards EMBO Member
Scientific career
Fields
Institutions
Thesis Antigen presentation by the B cell antigen receptor  (1994)
Doctoral advisor Michael Neuberger [5] [6]
Website

Ketan Jayakrishna Patel [1] FRS FMedSci MRCP [7] 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. [8] Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB). [9] [10] [11] [12] [13]

Education and early life

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. [1] 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 [5] 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. [14]

Career and Research

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. [12] 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. [15] 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. [16]

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 [3] [4] and, most recently, his lab discovered that reactive aldehydes are the likely natural agents that produce them. [17] [18] [19] [20] 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 Two-tier protection against genotoxic aldehydes (after KJ Patel).jpg
Two-tier protection against reactive aldehydes

Awards and honours

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). [21] 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 [22] 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. [7]

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.

Related Research Articles

<span class="mw-page-title-main">Fanconi anemia</span> Medical condition

Fanconi anaemia (FA) is a rare, AR, genetic disease resulting in impaired response to DNA damage in the FA/BRCA pathway. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), MDS, and liver tumors. 90% develop aplastic anemia by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. 60% of FA is FANC-A, 16q24.3, which has later onset bone marrow failure.

<span class="mw-page-title-main">MRC Laboratory of Molecular Biology</span> Research institute in Cambridge, England

The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical research laboratory at the forefront of scientific discovery, dedicated to improving the understanding of key biological processes at atomic, molecular and cellular levels using multidisciplinary methods, with a focus on using this knowledge to address key issues in human health.

<span class="mw-page-title-main">Fanconi anemia, complementation group C</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group C protein is a protein that in humans is encoded by the FANCC gene. This protein delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA. Mutations in this gene result in Fanconi anemia, a human rare disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages.

<span class="mw-page-title-main">FANCA</span> Protein-coding gene in the species Homo sapiens

Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the FANCA gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementation groups are currently recognized and is hypothesised to operate as a post-replication repair or a cell cycle checkpoint. FANCA proteins are involved in inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability that regulates the differentiation of haematopoietic stem cells into mature blood cells.

<span class="mw-page-title-main">FANCD2</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO.

<span class="mw-page-title-main">FANCG</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group G protein is a protein that in humans is encoded by the FANCG gene.

<span class="mw-page-title-main">ERCC4</span> Protein-coding gene in the species Homo sapiens

ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ERCC4 gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">FANCF</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group F protein is a protein that in humans is encoded by the FANCF gene.

<span class="mw-page-title-main">FANCE</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia, complementation group E protein is a protein that in humans is encoded by the FANCE gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA cross-linking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation groufcrp E.

<span class="mw-page-title-main">FANCL</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.

<span class="mw-page-title-main">FANCB</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group B protein is a protein that in humans is encoded by the FANCB gene.

<span class="mw-page-title-main">FANCI</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia, complementation group I (FANCI) also known as KIAA1794, is a protein which in humans is encoded by the FANCI gene. Mutations in the FANCI gene are known to cause Fanconi anemia.

<span class="mw-page-title-main">PALB2</span> Protein-coding gene in the species Homo sapiens

Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.

<span class="mw-page-title-main">SLX4</span> Protein involved in DNA repair

SLX4 is a protein involved in DNA repair, where it has important roles in the final steps of homologous recombination. Mutations in the gene are associated with the disease Fanconi anemia.

Simon Joseph Boulton is a British scientist who has made important contributions to the understanding of DNA repair and the treatment of cancer resulting from DNA damage. He currently occupies the position of Senior Scientist and group leader of the DSB Repair Metabolism Laboratory at the Francis Crick Institute, London. He is also an honorary Professor at University College London.

<span class="mw-page-title-main">FAN1</span> Protein-coding gene in the species Homo sapiens

FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease. It is thought to play an important role in the Fanconi Anemia (FA) pathway.

<span class="mw-page-title-main">Andrew N. J. McKenzie</span>

Andrew Neil James McKenzie is a molecular biologist and group leader in the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).

<span class="mw-page-title-main">Lori Passmore</span> Canadian/British scientist

Lori Anne Passmore is a Canadian/British cryo electron microscopist and structural biologist who works at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) at the University of Cambridge. She is known for her work on multiprotein complexes involved in gene expression and development of new supports for cryo-EM.

<span class="mw-page-title-main">Helen Walden</span> English structural biologist

Helen Walden is an English structural biologist who received the Colworth medal from the Biochemical Society in 2015. She was awarded European Molecular Biology Organization (EMBO) membership in 2022. She is a Professor of Structural Biology at the University of Glasgow and has made significant contributions to the Ubiquitination field.

Agata Smogorzewska is a Polish-born scientist. She is an associate professor at Rockefeller University, heading the Laboratory of Genome Maintenance. Her work primarily focuses on DNA interstrand crosslink repair and the diseases resulting from deficiencies in this repair pathway, including Fanconi anemia and karyomegalic interstitial nephritis.

References

  1. 1 2 3 "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.)
  2. ↑ "Ketan J. Patel CV". University of Cambridge. Archived from the original on 21 July 2013.
  3. 1 2 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.
  4. 1 2 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.
  5. 1 2 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.
  6. ↑ 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.
  7. 1 2 "Dr Ketan Patel FMedSci FRS". London: The Royal Society. Archived from the original on 2 May 2015.
  8. ↑ "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.
  9. ↑ 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.
  10. ↑ 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 logo PLoS transparent.svg
  11. ↑ Joenje, H (2011). "Metabolism: Alcohol, DNA and disease". Nature. 475 (7354): 45–6. doi: 10.1038/475045a . PMID   21734701.
  12. 1 2 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.
  13. ↑ 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.
  14. ↑ Patel, Ketan Jayakrishna (1994). Antigen presentation by the B cell antigen receptor (PhD thesis). University of Cambridge. OCLC   53650905.
  15. ↑ "Senior Academic Promotions, 1 October 2017 exercise: Appointments and titles". Cambridge University Reporter. 26 July 2017. Retrieved 17 November 2020.
  16. ↑ "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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ "Dr Ketan Patel FRS FMedSci". London: Academy of Medical Sciences. Archived from the original on 12 May 2015.
  22. ↑ "Dr Ketan Patel FRS". London: Royal Society. Archived from the original on 17 November 2015.
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