Personal profile
My research in a nutshell
Current Research Interests
My research focus is on host defence peptides. It has become clear to me that the dysregulation of innate immunity processes can lead to the destructive inflammation central to many (all) human diseases. Currently I am working on a multigene family of antimicrobial peptides called β-defensins which are astonishingly potent against yeast, bacteria and viruses and recognised as major players in innate immunity and yet deletion of these genes results in novel and exciting phenotypes. They are expressed at mucosal surfaces when induced but are highly expressed normally in male and female reproductive tract. I have shown that these molecules are both important in protection from infection and in immune modulation in vitro and in vivo. I have recently developed single gene, clade specific and whole locus deletions of these genes to reveal their full in vivo functional repertoire. I have recently published (Zhou et al 2013 (over 1,000 downloads in the first 2 weeks of publication) the profound male infertility phenotype we observe in mice when a subset of defensin genes are deleted and reveal a novel function of these genes in sperm maturation and control of calcium influx into sperm cells. This cluster of β-defensins in human (but not in mouse) is highly copy number variable (varies between 1 and 16 in human populations). The mutant derived sperm are precociously activated and show microtubule disruption and lack of motility. Deletion of the whole 31 gene locus is revealing a diverse series of inflammatory phenotypes and I am investigating their relevance to human disease.
Biography
- 1986-1989 CF Trust UK funded postdoctoral with Prof. Veronica van Heyningen. MRC HGU Edinburgh
- 1989-1992 CF Trust UK funded postdoctoral with Prof. David Porteous MRC HGU Edinburgh
- 1992-1995 Caledonian Fellowship Royal Society of Edinburgh MRC HGU Edinburgh
- 1995-2011 MRC Senior scientist (band 2) MRC Human Genetics Unit
- 2011-2015: Edinburgh University,: College of Medicine and Veterinary Science IGMM, Edinburgh Uni, MRC HGU Western General Hospital EH4 2XU
- 2015-Professor of Genetics of Host Defence MRC CIR
- Hours of work 1999-2001: 3 days per week
- 2001-2002: 4 days per week
- 2002-2006: 3.5 days per week
- 2006-2012: 4.5 days per week.
- March 2012-present: fulltime
- Four periods of maternity leave.
Education/Academic qualification
Doctor of Science, University of Edinburgh
Award Date: 1 Jan 1987
Bachelor of Science, Newcastle University
Award Date: 1 Jan 1983
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Collaborations and top research areas from the last five years
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Human β-D-3 Exacerbates MDA5 but Suppresses TLR3 Responses to the Viral Molecular Pattern Mimic Polyinosinic:Polycytidylic Acid
Semple, F., MacPherson, H., Webb, S., Kilanowski, F., Lettice, L., McGlasson, S. L., Wheeler, A. P., Chen, V., Millhauser, G. L., Melrose, L., Davidson, D. J. & Dorin, J. R., 8 Dec 2015, In: PLoS Genetics. 11, 12, e1005673.Research output: Contribution to journal › Article › peer-review
Open AccessFile -
The RNA-Editing Enzyme ADAR1 Controls Innate Immune Responses to RNA
Mannion, N. M., Greenwood, S. M., Young, R., Cox, S., Brindle, J., Read, D., Nellåker, C., Vesely, C., Ponting, C. P., McLaughlin, P. J., Jantsch, M. F., Dorin, J., Adams, I. R., Scadden, A. D. J., Öhman, M., Keegan, L. P. & O'Connell, M. A., 20 Nov 2014, In: Cell Reports. 9, 4, p. 1482-1494 13 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile -
Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice
Zhou, Y., Webb, S., Lettice, L., Tardif, S., Kilanowski, F., Tyrrell, C., MacPherson, H., Semple, F., Tennant, P., Baker, T., Hart, A., Devenney, P. S., Perry, P., Davey, T., Barran, P., Barratt, C. L. R. & Dorin, J., Oct 2013, In: PLoS Genetics. 9, 10, e1003826.Research output: Contribution to journal › Article › peer-review
Open AccessFile -
Enzymatic removal of ribonucleotides from DNA is essential for Mammalian genome integrity and development
Reijns, M. A. M., Rabe, B., Rigby, R. E., Mill, P., Astell, K. R., Lettice, L. A., Boyle, S., Leitch, A., Keighren, M., Kilanowski, F., Devenney, P. S., Sexton, D., Grimes, G., Holt, I. J., Hill, R. E., Taylor, M. S., Lawson, K. A., Dorin, J. R. & Jackson, A. P., 2012, In: Cell. 149, 5, p. 1008-22 15 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile -
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF
Semple, F., MacPherson, H., Webb, S., Cox, S. L., Mallin, L. J., Tyrrell, C., Grimes, G. R., Semple, C. A., Nix, M. A., Millhauser, G. L. & Dorin, J. R., 2011, In: European Journal of Immunology. 41, 11, p. 3291-300 10 p.Research output: Contribution to journal › Article › peer-review
Open AccessFile
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Restore- Reducing the barriers in correcting research outputs and stress of the Research Misconduct process in researchers
Dorai-Schneiders, T. (Principal Investigator) & Dorin, J. (Co-investigator)
1/08/25 → 31/05/26
Project: Research
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The Role of Defensins in Hidradenitis Suppurativa
Dorin, J. (Principal Investigator) & Tyrrell, K. (Co-investigator)
1/11/21 → 31/10/24
Project: Research
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The Role of Defensins in Hidradenitis Suppurativa
Dorin, J. (Principal Investigator) & Tyrrell, K. (Co-investigator)
1/11/21 → 18/01/26
Project: Research
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Human beta-defensin in Atopic Dermatitis: dissecting the mechanism of a novel, targetable, protection against barrier damage.
Davidson, D. (Principal Investigator), Dorin, J. (Co-investigator), McHugh, B. (Co-investigator) & Weller, R. (Co-investigator)
1/09/18 → 31/12/21
Project: Research
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Denny and the T team fight Cancer.
Dorin, J. (Principal Investigator) & Davidson, D. (Co-investigator)
1/10/17 → 30/09/18
Project: Research