缅北禁地

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Staff Profile

Professor Michael Briggs

Professor of Skeletal Genetics

  • Personal Website:
  • Address: Biosciences Institute
    缅北禁地
    International Centre for Life
    Central Parkway
    缅北禁地 upon Tyne
    NE1 3BZS
Background
Personal biography:

  • From October 1989 to September 1992, I was a PhD Student in the MRC Clinical Research Centre at Harrow investigating the molecular defects of type I collagen in osteogenesis imperfecta.
  • From October 1992 to October 1993, I was a Research Fellow in the Division of Medical Genetics at UCLA/Cedars Sinai Medical Centre. This was a 3-year Training Fellowship in the UCLA Intercampus Medical Genetics Training Program and the project involved the genetic mapping of PSACH and MED mutations in large families with these diseases. 
  • In July 1995, I was awarded a Research Fellowship from the Arthritis Research Campaign and moved to the University of Manchester. 
  • In January 2004, I started a 5-year Wellcome Trust Senior Research Fellowship (SRF) and during this time we studied the disease mechanisms of matrilin-3 and COMP mutations in vitro and generated of the first mouse models of PSACH-MED. In April 2008, I was awarded a 5-year renewal of my SRF. 
  • In June 2012 I moved to 缅北禁地 as Professor of Skeletal Genetics.
Research

Overview 

During endochondral bone growth, chondrocytes in the growth plate undergo a highly coordinated and tightly controlled process of proliferation, hypertrophy and finally apoptosis at the vascular invasion front. Chondrocyte proliferation and hypertrophy is vital for correct long bone growth, whilst apoptosis of terminal hypertrophic chondrocytes plays a critical role in the transition from chondrogenesis to osteogenesis. Disruptions to these processes lead to growth plate dysplasia and result in a heterogeneous group of genetic diseases known as skeletal dysplasias that are characterised predominantly by short-limb dwarfism.

The scientific story

At each stage of maturation in the growth plate, chondrocytes synthesise and secrete specific structural proteins that are incorporated into the extracellular matrix (ECM). For example, cartilage oligomeric matrix protein (COMP) and matrilin-3 are expressed to the greatest extent by resting and proliferative chondrocytes, whilst type X collagen is expressed exclusively by hypertrophic chondrocytes. The expression of mutant forms of these cartilage structural proteins causes endoplasmic reticulum (ER) stress and induces an unfolded protein response (UPR). Briefly, the UPR is a sophisticated quality control system that aims to reduce ER stress through the activation of a number of different pathways that are mediated by three receptors, IRE1, ATF6 and PERK, and involving other downstream factors such as Xbp-1 and eIF2a. However, if ER homeostasis is not achieved then prolonged ER stress can eventually result in CHOP-mediated apoptosis.

We have shown using genetically engineered mouse models that the induction of ER stress and the UPR, through the expression of mutant COMP, matrilin-3 and type X collagen, can directly affect chondrocyte phenotype and cause growth plate dysplasia leading to short-limb dwarfism. Interestingly, although these mouse models all exhibit ER stress and an UPR, the different pathways that are activated appear to be gene and/or mutation specific. It is not clear in these archetypal examples of prolonged ER stress, whether the UPR is chondrocyte protective or a significant cause of distress. Answering this fundamental question will not only explain the initiation and progression of skeletal dysplasias, but will provide essential insight into disease mechanisms in many different diseases in which ER stress and UPR has been implicated.



Publications

  • Articles

    • Dennis EP, Watson RN, McPate F, Briggs MD. . International Journal of Molecular Sciences 2023, 24(2), 1496.
    • Duxfield A, Munkley J, Briggs MD, Dennis EP. . Scientific Reports 2022, 12(1), 13884.
    • Hayman DJ, Modebadze T, Charlton S, Cheung K, Soul J, Lin H, Hao Y, Miles CG, Tsompani D, Jackson RM, Briggs MD, Piróg KA, Clark IM, Barter MJ, Clowry GJ, LeBeau FEN, Young DA. . Scientific Reports 2021, 11(1), 10452.
    • Dennis EP, Edwards SM, Jackson RM, Hartley CL, Tsompani D, Capulli M, Teti A, Boot-Handford RP, Young DA, Piróg KA, Briggs MD. . Journal of Bone and Mineral Research 2020, 35(8), 1452-1469.
    • Piróg KA, Dennis EP, Hartley CL, Jackson RM, Soul J, Schwartz JM, Bateman JF, Boot-Handford RP, Briggs MD. . PLoS Genetics 2019, 15(7), e1008215.
    • Kung LHW, Mullan L, Soul J, Wang P, Mori K, Bateman JF, Briggs MD, Boot-Handford RP. . Arthritis Research and Therapy 2019, 21(1), 206.
    • Bell PA, Dennis EP, Hartley CL, Jackson RM, Porter A, Boot-Handford RP, Pirog KA, Briggs MD. . Cell Stress and Chaperones 2018, 24(1), 159-173.
    • Mullan LA, Mularczyk EJ, Kung LH, Forouhan M, Wragg JM, Goodacre R, Bateman JF, Swanton E, Briggs MD, Boot-Handford RP. . Journal of Clinical Investigation 2017, 127(10), 3861-3865.
    • Briggs MD, Bell PA, Wright MJ, Pirog KA. . Expert Opinion on Orphan Drugs 2015, 3(10), 1137-1154.
    • Kung LHW, Rajpar MH, Preziosi R, Briggs MD, Boot-Handford RP. . PLoS ONE 2015, 10(2), e0117016.
    • Cameron TL, Gresshoff IL, Bell KM, Piróg KA, Sampurno L, Hartley CL, Sanford EM, Wilson R, Ermann J, Boot-Handford RP, Glimcher LH, Briggs MD, Bateman JF. . Osteoarthritis and Cartilage 2015, 23(4), 661-670.
    • Briggs MD, Brock J, Ramsden SC, Bell PA. . European Journal of Human Genetics 2014, 22(11), 1278-1282.
    • Piróg KA, Irman A, Young S, Halai P, Bell PA, Boot-Handford RP, Briggs MD. . PLoS One 2014, 9(2), e85145.
    • Piróg KA, Katakura Y, Mironov A, Briggs MD. . PLoS One 2013, 8(11), e82412.
    • Hartley CL, Edwards S, Mullan L, Bell PA, Fresquet M, Boot-Handford RP, Briggs MD. . Human Molecular Genetics 2013, 22, 5262-5275.
    • Bell PA, Wagener R, Zaucke F, Koch M, Selley J, Warwood S, Knight D, Boot-Handford RP, Thornton DJ, Briggs MD. . Biology Open 2013, 2(8), 802-811.
    • Gualeni B, Rajpar MH, Kellogg A, Bell PA, Arvan P, Boot-Handford RP, Briggs MD. . Disease Models & Mechanisms 2013, 6(6), 1414-1425.
    • Boyden ED, Campos-Xavier AB, Kalamajski S, Cameron TL, Suarez P, Tanackovic G, Andria G, Ballhausen D, Briggs MD, Hartley C, Cohn DH, Davidson HR, Hall C, Ikegawa S, Jouk PS, Konig R, Megarbane A, Nishimura G, Lachman RS, Mortier G, Rimoin DL, Rogers RC, Rossi M, Sawada H, Scott R, Unger S, Valadares ER, Bateman JF, Warman ML, Superti-Furga A, Bonafe L. . American Journal of Human Genetics 2012, 90(1), 170.
    • Jackson G, Mittaz-Crettol L, Taylor J, Mortier G, Spranger J, Zabel B, Le Merrer M, Cormier-Daire V, Hall C, Offiah A, Wright M, Savarirayan R, Nishimura G, Ramsden S, Elles R, Bonafe L, Superti-Furga A, Unger S, Zankl A, Briggs M. . Human Mutation 2012, 33(1), 144-157.
    • Bell PA, Piróg KA, Fresquet M, Thornton DJ, Boot-Handford RP, Briggs MD. . Arthritis & Rheumatism 2012, 64(5), 1529-1539.
    • Suleman F, Gualeni B, Gregson HJ, Leighton MP, Piróg KA, Edwards S, Holden P, Boot-Handford RP, Briggs MD. . Human Mutation 2012, 33(1), 218-231.
    • Boyden ED, Campos-Xavier AB, Kalamajski S, Cameron TL, Suarez P, Tanackovich G, Andria G, Ballhausen D, Briggs MD, Hartley C, Cohn DH, Davidson HR, Hal C, Ikegawa S, Jouk PS, Konig R, Megarbane A, Nishimura G, Lachman RS, Mortier G, Rimoin DL, Rogers RC, Rossi M, Sawada H, Scott R, Unger S, Valadares ER, Bateman JF, Warman ML, Superti-Furga A, Bonafe L. . American Journal of Human Genetics 2011, 89(6), 767-772.
    • Jackson GD, Marcus-Soekarman D, Stolte-Dijkstra I, Verrips A, Taylor JA, Briggs MD. . American Journal of Medical Genetics Part A 2010, 152A(4), 863-869.
    • Boot-Handford RP, Briggs M. . Cell and Tissue Research 2010, 339(1), 197-211.
    • Fresquet M, Jowitt TA, Stephen LA, Ylostalo J, Briggs MD. . Journal of Biological Chemistry 2010, 285(44), 34048-34061.
    • Pirog KA, Briggs MD. . Journal of Biomedicine and Biotechnology 2010, Article no. 686457.
    • Nundlall S, Rajpar MH, Bell PA, Clowes C, Zeeff LAH, Gardner B, Thornton DJ, Boot-Handford RP, Briggs MD. . Cell Stress and Chaperones 2010, 15(6), 835-849.
    • Piróg KA, Jaka O, Katakura Y, Meadows RS, Kadler KE, Boot-Handford RP, Briggs MD. . Human Molecular Genetics 2010, 19(1), 52-64.
    • Rajpar MH, McDermott B, Kung L, Eardley R, Knowles L, Heeran M, Thornton DJ, Wilson R, Bateman JF, Poulsom R, Arvan P, Kadler KE, Briggs MD, Boot-Handford RP. . PLoS Genetics 2009, 5(10), e1000691.
    • Tompson S, Merriman B, Funari VA, Fresquet M, Lachman RS, Rimoin DL, Nelson SF, Briggs MD, Cohn DH, Krakow D. . American Journal of Human Genetics 2009, 84(1), 72-79.
    • Fresquet M, Jackson GC, Loughlin J, Briggs MD. . Human Mutation 2008, 29(2), 330.
    • Saeed S, Briggs M, Lobo C, Al-Zoubi F, Ramsden R, Read A. . Otosclerosis and Stapes Surgery 2007, 65, 75-85.
    • Fresquet M, Jowitt TA, Ylostalo J, Coffey P, Meadows RS, Ala-Kokko L, Thornton DJ, Briggs MD. . Journal of Biological Chemistry 2007, 282(48), 34634-34643.
    • Pirog-Garcia KA, Meadows RS, Knowles L, Heinegard D, Thornton DJ, Kadler KE, Boot-Handford RP, Briggs MD. . Human Molecular Genetics 2007, 16(17), 2072-2088.
    • Zankl A, Jackson GC, Crettol LM, Taylor J, Elles R, Mortier GR, Spranger J, Zabel B, Unger S, Le Merrer M, Cormier-Daire V, Hall CM, Wright MJ, Bonafe L, Superti-Furga A, Briggs MD. . European Journal of Human Genetics 2007, 15(2), 150-154.
    • Leighton MP, Nundlall S, Starborg T, Meadows RS, Suleman F, Knowles L, Wagener R, Thornton DJ, Kadler KE, Boot-Handford RP, Briggs MD. . Human Molecular Genetics 2007, 16(14), 1728-1741.
    • Plumb DA, Dhir V, Mironov A, Ferrara L, Poulsom R, Kadler KE, Thornton DJ, Briggs MD, Boot-Handford RP. . Journal of Biological Chemistry 2007, 282(17), 12791-12795.
    • Kennedy J, Jackson GC, Barker FS, Nundlall S, Bella J, Wright MJ, Mortier GR, Neas K, Thompson E, Elles R, Briggs MD. . Human Mutation 2005, 25(6), 593-594.
    • Jakkula E, Makitie O, Czarny-Ratajczak M, Jackson GC, Damignani R, Susic M, Briggs MD, Cole WG, Ala-Kokko L. . European Journal of Human Genetics 2005, 13(10), 1166-1166.
    • Cotterill SL, Jackson GC, Leighton MR, Wagener R, Makitie O, Cole WG, Briggs MD. . Human Mutation 2005, 26(6), 557-565.
    • Kennedy J, Jackson G, Ramsden S, Taylor J, Newman W, Wright MJ, Donnai D, Elles R, Briggs MD. . European Journal of Human Genetics 2005, 13(5), 547-555.
    • Spranger JW, Zabel B, Kennedy J, Jackson G, Briggs M. . American Journal of Medical Genetics Part A 2005, 132A(1), 20-24.
    • Jackson GC, Barker FS, Jakkula E, Czarny-Ratajczak M, Makitie O, Cole WG, Wright MJ, Smithson SF, Suri M, Rogala P, Mortier GR, Baldock C, Wallace A, Elles R, Ala-Kokko L, Briggs MD. . Journal of Medical Genetics 2004, 41(1), 52-59.
    • Makitie O, Mortier GR, Czarny-Ratajczak M, Wright MJ, Suri M, Rogala P, Freund M, Jackson GC, Jakkula E, Ala-Kokko L, Briggs MD, Cole WG. . American Journal of Medical Genetics Part A 2004, 125(3), 278-284.
    • Briggs MD, Chapman KL. . Human Molecular Genetics 2002, 19(5), 465-478.
    • Chapman KL, Mortier GR, Chapman K, Loughlin J, Grant ME, Briggs MD. . Nature Genetics 2001, 28(4), 393-396.
    • Mortier GR, Chapman K, Leroy JL, Briggs MD. . European Journal of Human Genetics 2001, 9(8), 606-612.
    • Holden P, Meadows RS, Chapman KL, Grant ME, Kadler KE, Briggs MD. . Journal of Biological Chemistry 2001, 276(8), 6046-6055.
    • Newman B, Donnai D, Briggs MD. . Journal of Medical Genetics 2000, 37(1), 64-65.
    • Reardon AJ, LeGoff M, Briggs MD, McLeod D, Sheehan JK, Thornton DJ, Bishop PN. . Journal of Biological Chemistry 2000, 275(3), 2123-2129.
    • Spayde EC, Joshi AP, Wilcox WR, Briggs M, Cohn DH, Olsen BR. . Matrix Biology 2000, 19(2), 121-128.
    • Delot E, King LM, Briggs MD, Wilcox WR, Cohn DH. . Human Molecular Genetics 1999, 8(1), 123-128.
    • Holden P, Canty EG, Mortier GR, Zabel B, Spranger J, Carr A, Grant ME, Loughlin JA, Briggs MD. . American Journal of Human Genetics 1999, 65(1), 31-38.
    • Loughlin J, Irven C, Mustafa Z, Briggs MD, Carr A, Lynch SA, Knowlton RG, Cohn DH, Sykes B. Identification of five novel mutations in cartilage oligomeric matrix protein gene in pseudoachrondroplasia and multiple epiphyseal dysplasia. Human Mutation 1998, (s1), S10-S17.
    • Briggs MD, Mortier GR, Cole WG, King LM, Golik SS, Bonaventure J, Nuytinck L, DePaepe A, Leroy JG, Biesecker L, Lipson M, Wilcox WR, Lachman RS, Rimoin DL, Knowlton RG, Cohn DH. Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia multiple epiphyseal dysplasia disease spectrum. American Journal of Human Genetics 1998, 62(2), 311-319.
    • Ballo R, Briggs MD, Cohn DH, Knowlton RG, Beighton PH, Ramesar RS. Multiple epiphyseal dysplasia, ribbing type: A novel point mutation in the COMP gene in a South African family. American Journal of Medical Genetics 1997, 68(4), 396-400.
    • Briggs MD, Hoffman SMG, King LM, Olsen AS, Mohrenweiser H, Leroy JG, Mortier GR, Rimoin DL, Lachman RS, Gaines ES, Cekleniak JA, Knowlton RG, Cohn DH. Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nature Genetics 1995, 10(3), 330-336.
    • Knowlton RG, Cekleniak JA, Cohn DH, Briggs MD, Hoffman SMG, Brandriff BF, Olsen AS. High-resolution genetic and physical mapping of multiple epiphyseal dysplasia and pseudoachondroplasia mutations at chromosome 19p13.1-p12. Genomics 1995, 28(3), 513-519.
    • Briggs MD, Choi HC, Warman ML, Loughlin JA, Wordsworth P, Sykes BC, Irven CMM, Smith M, Wynnedavies R, Lipson MH, Biesecker LG, Garber AP, Lachman R, Olsen BR, Rimoin DL, Cohn DH. Genetic-mapping of a locus for multiple epiphyseal dysplasia (edm2) to a region of chromosome-i containing a type ix collagen gene. American Journal Of Human Genetics 1994, 55(4), 678-684.
    • Rimoin DL, Rasmussen IM, Briggs MD, Roughley PJ, Gruber HE, Warman ML, Olsen BR, Hsia YE, Yuen J, Reinker K, Garber AP, Grover J, Lachman RS, Cohn DH. A large family with features of pseudoachondroplasia and multiple epiphyseal dysplasia - exclusion of 7 candidate gene loci that encode proteins of the cartilage extracellular-matrix. Human Genetics 1994, 93(3), 236-242.
    • Hecht JT, Francomano CA, Briggs MD, Deere M, Conner B, Horton WA, Warman M, Cohn DH, Blanton SH. Linkage of typical pseudoachondroplasia to chromosome-19. Genomics 1993, 18(3), 661-666.
    • Briggs MD, Rasmussen IM, Weber JL, Yuen J, Reinker K, Garber AP, Rimoin DL, Cohn DH. Genetic-linkage of mild pseudoachondroplasia (psach) to markers in the pericentromeric region of chromosome-19. Genomics 1993, 18(3), 656-660.

  • Book Chapters

    • Briggs MD, Bell PA, Piróg KA. . In: Grässel S; Aszódi A, ed. Cartilage. Springer International Publishing AG, 2017, pp.135-153.
    • Briggs MD. . In: Streuli, C., Grant, M, ed. Extracellular Matrix Protocols. London: Humana Press, 2000, pp.133-145.

  • Conference Proceedings (inc. Abstracts)

    • Dennis EP, Capulli M, Teti A, Pirog KA, Briggs MD. . In: 43rd Annual European Calcified Tissue Society Congress. 2016, Rome, Italy: Bone Abstracts.
    • Boot-Handford RP, Kung LH, Mullan L, Mularczyk EJ, Briggs MD. . In: 2016 OARSI World Congress on Osteoarthritis: Promoting Clinical and Basic Research in Osteoarthritis. 2016, Amsterdam, The Netherlands: Elsevier.
    • Gibson BG, Sonntag S, Selbert S, Pirog KA, Briggs MD. . In: British Society for Matrix Biology / Bone Research Society Third Joint Meeting. 2015, Edinburgh: Wiley-Blackwell Publishing Ltd.
    • Dennis EP, Edwards SM, Boot-Handford RP, Pirog KA, Briggs MD. . In: British Society for Matrix Biology / Bone Research Society Third Joint Meeting. 2015, Edinburgh: Wiley-Blackwell Publishing Ltd.
    • Jackson RM, Bell PA, Briggs MD. . In: British Society for Matrix Biology / Bone Research Society Third Joint Meeting. 2015, Edinburgh: Wiley-Blackwell Publishing Ltd.
    • Pirog KA, Meadows RS, Boot-Handford RP, Briggs MD. . In: British Society for Matrix Biology Autumn 2013 Meeting. 2013, Cardiff: Wiley-Blackwell.
    • Kung LHW, Mullan L, Briggs MD, Boot-Handford RP. . In: British Society for Matrix Biology Autumn 2013 Meeting. 2013, Cardiff: Wiley-Blackwell.
    • Unger SL, Briggs MD, Holden P, Zabel B, Ala-Kokko L, Paassilta P, Lohiniva J, Rimoin DL, Lachman RS, Cohn DH. . In: 4th International Skeletal Dysplasia Meeting. 2001, Baden Baden, Germany: Springer.
    • Cohn DH, Briggs MD, King LM, Rimoin DL, Wilcox WR, Lachman RS, Knowlton RG. . In: Molecular and Developmental Biology of Cartilage. 1996, Bethesda, Maryland, USA: New York Academy of Sciences.

  • Reviews

    • Dennis EP, Greenhalgh-Maychell PL, Briggs MD. . Developmental Dynamics 2021, 250(3), 345-359.
    • Briggs MD, Dennis EP, Dietmar H, Pirog KA. . F1000Research 2020, 9, 290.
    • Gibson BG, Briggs MD. . Orphanet Journal of Rare Diseases 2016, 11, 86.
    • Briggs MD, Bell PA, Pirog KA. . International Journal of Molecular Medicine 2015, 1483-1492.
    • Chapman KL, Briggs MD, Mortier GR. . Pediatric Pathology and Molecular Medicine 2003, 22(1), 53-75.