Dr. David Mottershead

Title: Lecturer in Biochemistry & Cell Biology
Phone: 01782 734764
Email: d.mottershead@keele.ac.uk
Location: Hornbeam Building, Room 2.32
Role: ISTM Research theme: Therapeutics
Contacting me: Try my office or arrange an appointment via e-mail

I joined the School of Pharmacy as a Lecturer in Biochemistry & Cell Biology at the beginning of 2016. From the beginning of 2009 until 2014 I was a Senior Research Fellow in the School of Paediatrics and Reproductive Health, at the University of Adelaide (Australia) heading up a group researching the oocyte-secreted factors GDF9 and BMP15. More recently (2015) I established a biotech consulting company (Mottasis Oy Ltd) based in Helsinki, Finland, specializing in the area of mammalian cell expression of recombinant proteins. My PhD research was carried out in the Biochemistry Dept. at the University of Adelaide (1990), which was followed by a number of Postdoc positions (Boston (USA), Sydney (Australia), Helsinki (Finland)). My research interests remain in particular with the growth factors GDF9 & BMP15, focussing on structure/function relationships, signal transduction mechanisms and the development of novel forms with applications for infertility treatment. 

ISTM Research theme: Therapeutics

In my research I focus on two growth factors produced by oocytes and which are essential for fertility in mammals, namely growth differentiation factor 9 (GDF9) and bone morphogenetic factor 15 (BMP15). These two proteins are members of the large transforming growth factor beta (TGF-b) family which share structural similarities and mechanisms of action. Recently, our group at the University of Adelaide demonstrated a unique mechanism of action critical for signalling by human GDF9, resulting in the production of a new form of the protein which we have called Cumulin. Following on from this work, the molecular mechanisms of action of Cumulin (a form of heterodimer of GDF9 & BMP15) need to be elucidated and forms produced for applications in the area of infertility treatment. 

Please see the web links below to media reoprts on the use of the protein Cumulin.

http://theconversation.com/emerging-infertility-treatment-could-be-a-less-invasive-and-cheaper-alternative-to-ivf-63831

https://www.newscientist.com/article/2102026-drug-free-ivf-could-be-cheaper-and-faster-way-to-get-pregnant/

http://www.abc.net.au/news/2016-08-24/in-vitro-treatment-avoids-hormone-injections-researchers-say/7778908

http://www.ibtimes.co.uk/potent-new-fertility-technique-prevents-side-effects-vitro-fertilisation-women-1577610

http://www.dailymail.co.uk/health/article-3754639/Fresh-hope-childless-couples-Scientists-develop-potent-fertility-treatment-cheaper-IVF-fewer-effects.html

YouTube clip highlighting the use of Cumulin in IVM:

https://www.youtube.com/watch?v=5xnBXWOdwT0

Selected Publications

  • Sharkey DJ, Schjenken JE, Mottershead DG, Robertson SA. 2015. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells. Mol Cell Endocrinol, vol. 417, 178-190. link> doi>
  • Mottershead DG, Sugimura S, Al-Musawi SL, Li J-J, Richani D, White MA, Martin GA, Trotta AP, Ritter LJ, Shi J, Mueller TD, Harrison CA, Gilchrist RB. 2015. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality. J Biol Chem, vol. 290(39), 24007-24020. link> doi>
  • Sugimura S, Ritter LJ, Rose RD, Thompson JG, Smitz J, Mottershead DG, Gilchrist RB. 2015. Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes. Dev Biol, vol. 403(2), 139-149. link> doi>
  • Sutton-McDowall ML, Purdey M, Brown HM, Abell AD, Mottershead DG, Cetica PD, Dalvit GC, Goldys EM, Gilchrist RB, Gardner DK, Thompson JG. 2015. Redox and anti-oxidant state within cattle oocytes following in vitro maturation with bone morphogenetic protein 15 and follicle stimulating hormone. Mol Reprod Dev, vol. 82(4), 281-294. link> doi>
  • Li J, Sugimura S, Mueller TD, White MA, Martin GA, Ritter LJ, Liang X, Gilchrist RB, Mottershead D. 2014. Modifications of human growth differentiation factor 9 to improve the generation of embryos from low competence oocytes. Molecular Endocrinology, vol. 29(1). doi>

Full Publications List show

Journal Articles

  • Sharkey DJ, Schjenken JE, Mottershead DG, Robertson SA. 2015. Seminal fluid factors regulate activin A and follistatin synthesis in female cervical epithelial cells. Mol Cell Endocrinol, vol. 417, 178-190. link> doi>
  • Mottershead DG, Sugimura S, Al-Musawi SL, Li J-J, Richani D, White MA, Martin GA, Trotta AP, Ritter LJ, Shi J, Mueller TD, Harrison CA, Gilchrist RB. 2015. Cumulin, an Oocyte-secreted Heterodimer of the Transforming Growth Factor-β Family, Is a Potent Activator of Granulosa Cells and Improves Oocyte Quality. J Biol Chem, vol. 290(39), 24007-24020. link> doi>
  • Sugimura S, Ritter LJ, Rose RD, Thompson JG, Smitz J, Mottershead DG, Gilchrist RB. 2015. Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes. Dev Biol, vol. 403(2), 139-149. link> doi>
  • Sutton-McDowall ML, Purdey M, Brown HM, Abell AD, Mottershead DG, Cetica PD, Dalvit GC, Goldys EM, Gilchrist RB, Gardner DK, Thompson JG. 2015. Redox and anti-oxidant state within cattle oocytes following in vitro maturation with bone morphogenetic protein 15 and follicle stimulating hormone. Mol Reprod Dev, vol. 82(4), 281-294. link> doi>
  • Li J, Sugimura S, Mueller TD, White MA, Martin GA, Ritter LJ, Liang X, Gilchrist RB, Mottershead D. 2014. Modifications of human growth differentiation factor 9 to improve the generation of embryos from low competence oocytes. Molecular Endocrinology, vol. 29(1). doi>
  • Reader KL, Mottershead DG, Martin GA, Gilchrist RB, Heath DA, McNatty KP, Juengel JL. 2016. Signalling pathways involved in the synergistic effects of human growth differentiation factor 9 and bone morphogenetic protein 15. Reprod Fertil Dev, vol. 28(4), 491-498. link> doi>
  • Sudiman J, Sutton-McDowall ML, Ritter LJ, White MA, Mottershead DG, Thompson JG, Gilchrist RB. 2014. Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence. PLoS One, vol. 9(7), e103563. link> doi> full text>
  • Tuck AR, Mottershead DG, Fernandes HA, Norman RJ, Tilley WD, Robker RL, Hickey TE. 2015. Mouse GDF9 decreases KITL gene expression in human granulosa cells. Endocrine, vol. 48(2), 686-695. link> doi>
  • Simpson CM, Robertson DM, Al-Musawi SL, Heath DA, McNatty KP, Ritter LJ, Mottershead DG, Gilchrist RB, Harrison CA, Stanton PG. 2014. Aberrant GDF9 expression and activation are associated with common human ovarian disorders. J Clin Endocrinol Metab, vol. 99(4), E615-E624. link> doi>
  • Sudiman J, Ritter LJ, Feil DK, Wang X, Chan K, Mottershead DG, Robertson DM, Thompson JG, Gilchrist RB. 2014. Effects of differing oocyte-secreted factors during mouse in vitro maturation on subsequent embryo and fetal development. J Assist Reprod Genet, vol. 31(3), 295-306. link> doi>
  • Sugimura S, Ritter LJ, Sutton-McDowall ML, Mottershead DG, Thompson JG, Gilchrist RB. 2014. Amphiregulin co-operates with bone morphogenetic protein 15 to increase bovine oocyte developmental competence: effects on gap junction-mediated metabolite supply. Mol Hum Reprod, vol. 20(6), 499-513. link> doi>
  • Simpson CM, Robertson DM, Heath DA, Ritter LJ, Mottershead D, Gilchrist RB, Harrison CA, Stanton PG. 2014. Aberrant GDF9 expression and activation is associated with human ovarian disorders. Endocrinology, vol. 99(4). doi>
  • Mottershead DG, Harrison CA, Mueller TD, Stanton PG, Gilchrist RB, McNatty KP. 2013. Growth differentiation factor 9:bone morphogenetic protein 15 (GDF9:BMP15) synergism and protein heterodimerization. Proc Natl Acad Sci U S A, vol. 110(25), E2257. link> doi> full text>
  • Sutton-McDowall ML, Mottershead D, Gardner DK, Gilchrist RB, Thompson JG. 2012. Metabolic differences in bovine cumulus oocyte complexes matured in vitro in the presence or absence of follicle stimulating hormone and bone morphogenetic protein 15. Biology of Reproduction, vol. 87(4). doi>
  • Watson LN, Mottershead D, Dunning KR, Robker RL, Gilchrist RB, Russell DL. 2012. Heparan sulfate proteoglycans regulate responses to oocyte paracrine signals in ovarian follicle morphogenesis. Endocrinology, vol. 153(9). doi>
  • Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA. 2012. TGF-β mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol, vol. 189(2), 1024-1035. link> doi>
  • Pulkki MM, Mottershead DG, Pasternack AH, Muggalla P, Ludlow H, van Dinther M, Myllymaa S, Koli K, ten Dijke P, Laitinen M, Ritvos O. 2012. A covalently dimerized recombinant human bone morphogenetic protein-15 variant identifies bone morphogenetic protein receptor type 1B as a key cell surface receptor on ovarian granulosa cells. Endocrinology, vol. 153(3), 1509-1518. link> doi>
  • Pulkki MM, Mottershead D, Pasternack AH, Muggalla P, Ludlow H, van Dinther M, Myllymaa S, Koli K, ten Dijke P, Laitinen M, Ritvos O. 2012. A covalently dimerized recombinant human bone morphogenetic protein-15 variant identifies bone morphogenetic protein receptor type 1B as a key cell surface receptor on ovarian granulosa cells. Endocrinology, vol. 153(3). doi>
  • Mottershead DG, Ritter LJ, Gilchrist RB. 2012. Signalling pathways mediating specific synergistic interactions between GDF9 and BMP15. Mol Hum Reprod, vol. 18(3), 121-128. link> doi>
  • Gilchrist RB, Mottershead D, Thompson JG. 2011. Oocyte maturation and ovulation - an orchestral symphony of signalling. Australian Biochemist, vol. 42(1), 8-11.
  • Pulkki MM, Myllymaa S, Pasternack A, Lun S, Ludlow H, Al-Qahtani A, Korchynskyi O, Groome N, Juengel JL, Kalkkinen N, Laitinen M, Ritvos O, Mottershead DG. 2011. The bioactivity of human bone morphogenetic protein-15 is sensitive to C-terminal modification: characterization of the purified untagged processed mature region. Mol Cell Endocrinol, vol. 332(1-2), 106-115. link> doi>
  • Sasseville M, Ritter LJ, Nguyen TM, Liu F, Mottershead DG, Russell DL, Gilchrist RB. 2010. Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells. J Cell Sci, vol. 123(Pt 18), 3166-3176. link> doi>
  • Myllymaa S, Pasternack A, Mottershead D, Poutanen M, Pulkki MM, Pelliniemi L, Ritvos O, Laitinen MP. 2010. Inhibition of oocyte growth factors in vivo modulates ovarian folliculgenesis in neonatal and immature mice. Reproduction, vol. 139, 587-598. doi>
  • Mottershead DG and Watson AJ. 2009. Oocyte peptides as paracrine tools for ovarian stimulation and oocyte maturation. Mol Hum Reprod, vol. 15(12), 789-794. link> doi>
  • Mottershead D, Pulkki MM, Muggalla P, Pasternack A, Tolonen M, Myllymaa S, Korchynskyi O, Nishi Y, Yanase T, Lun S, Juengel JL, Laitinen M, Ritvos O. 2007. Characterization of recombinant human growth differentiation factor-9 signaling in ovarian granulosa cells. Molecular and Cellular Endocrinology, vol. 283(1-2). doi>
  • Gilchrist RB, Ritter LJ, Myllymaa S, Kaivo-Oja N, Dragovic RA, Hickey TE, Ritvos O, Mottershead DG. 2006. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J Cell Sci, vol. 119(Pt 18), 3811-3821. link> doi>
  • Kaivo-Oja N, Jeffery LA, Ritvos O, Mottershead D. 2006. Smad signalling in the ovary. Reproductive Biology and Endocrinology, vol. 4(21). doi> full text>
  • McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead D, Groome NP, Ritvos O, Laitinen MP. 2005. Bone morphogenetic protein 15 and growth differentiation factor 9 interact to regulate granulosa cell function. Reproduction, vol. 129, 473-480. doi>
  • McNatty KP, Jeungel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, Western A, Meerasahib MF, Mottershead D, Groome NP, Ritvos O, Laitinen MP. 2005. Bone morphogenetic protein 15 and growth differentiation factor 9 interact to regulate granulosa cell function in ruminants. Reproduction, vol. 129, 481-487. doi>
  • Kaivo-Oja N, Mottershead D, Mazerbourg S, Myllymaa S, Duprat S, Gilchrist RB, Groome NP, Hsueh AJ, Ritvos O. 2013. Adenoviral gene transfer allows Smad responsive gene promoter analyses and delineation of type 1 receptor usage of transforming growth factor-B family ligands in cultured human granulosa-luteal cells. The Journal of Clinical Endocrinology and Metabolism, vol. 90(1). doi>
  • Gilchrist RB, Ritter LJ, Cranfield M, Jeffrey LA, Amato F, Scott SJ, Myllymaa S, Kaivo-Oja N, Lankinen H, Mottershead D, Groome NP, Ritvos O. 2004. Immunoneutralization of growth differentiation factor-9 reveals it partially accounts for mouse occyte mitogenic activity. Biology of Reproduction, vol. 71(3), 732-739. doi>
  • Mazerbourg S, Klein C, Roh J, Kaivo-Oja N, Mottershead D, Korchynskyi O, Ritvos O, Hsueh AJ. 2013. Growth differentiation factor-9 (GDF-9) signaling is mediated by the type 1 receptor, activin receptor-like kinase 5. Molecular Endocrinology, vol. 18(3). doi>
  • Mottershead D, Coleman SK, Cai C, Haapalahti JP, Keinanen K. 2003. Surface expression of GluR-D AMPA receptor is dependent upon an interaction between its C-terminal domain and a 4.1 protein. The Journal of Neuroscience, vol. 23(3), 798-806.
  • Joupilla A, Pentikainen OT, Settimo L, Nyronen JP, Haapalahti JP, Lampinen M, Mottershead D, Johnson MS, Keinanen K. 2002. Determinants of antagonist binding at the a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor: Role of the conserved Arg-507 and Glu-727 residues. The FEBS Journal, vol. 269(24), 6261-6270. doi>
  • Pasternack A, Coleman SK, Jouppila A, Mottershead D, Lindfors M, Pasternack M, Keinanen K. 2002. AMPA receptor channels lacking the N-terminal domain. Journal of Biological Chemistry, vol. 277, 49662-49667. doi>
  • Lampinen M, Pentikainen O, Settimo L, Mottershead D, Johnson M, Keinanen K. 2002. Discrimination between agonists and antagonists by the a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid selective glutamate receptor: an alanine scanning mutagenesis study. Journal of Biological Chemistry, vol. 277.
  • Ojala K, Mottershead D, Suokko A, Oker-Blom C. 2001. Specific Binding of Baculoviruses Displaying gp64 Fusion Proteins to Mammalian Cells. Biochemical and Biophysical Research Communications, vol. 284(3). doi>
  • Mottershead D, Alfthan K, Ojala K, Takkinen K, Oker-Blom C. 2000. Baculoviral Display of Functional scFv and Synthetic IgG-Binding Domains. Biochemical and Biophysical Research Communications, vol. 275(1). doi>
  • Mottershead D, Polly P, Lyons RJ, Sutherland RL, Watts CKW. 1996. High Activity, Soluble, Bacterially Expressed Human Vitamin D Receptor and its Ligand Binding Domain. Journal of Cell Biochemistry, vol. 61(1), 325-337.
  • Mottershead D, Hsu PN, Urban RG, Strominger JL, Huber BT. 1995. Direct Binding of the Mtv-7 Superantigen (M1s-1) to Soluble MHC Class II Molecules. Immunity, vol. 2, 149-154.
  • Szabo L, Mottershead D, Ballard FJ, Wallace JC. 1988. The Bovine Insulin-like Growth Factor (IGF) Binding Protein Purified from Conditioned Medium Requires the N-terminal Tripepide in IGF-1 for Binding. Biochemical and Biophysical Research Communications, vol. 151(1), 207-214. doi>
  • Haruyama T, Bongsebandhu-Phubhakdi S, Nakamura I, Mottershead D, Keinänen K, Kobatake E, Aizawa M. 2003. A biosensing system based on extracellular potential recording of ligand-gated ion channel function overexpressed in insect cells. Anal Chem, vol. 75(4), 918-921. link> doi>
  • Mottershead D, van der Linden I, von Bonsdorff CH, Keinänen K, Oker-Blom C. 1997. Baculoviral display of the green fluorescent protein and rubella virus envelope proteins. Biochem Biophys Res Commun, vol. 238(3), 717-722. link> doi>
  • Orellana A, Mottershead D, van der Linden I, Keinänen K, Oker-Blom C. 1999. Mimicking rubella virus particles by using recombinant envelope glycoproteins and liposomes. J Biotechnol, vol. 75(2-3), 209-219. link> doi>
  • Subramanyam M, Mohan N, Mottershead D, Beutner U, McLellan B, Kraus E, Huber BT. 1993. Mls-1 superantigen: molecular characterization and functional analysis. Immunol Rev, vol. 131, 117-130. link> doi>
  • Mohan N, Mottershead D, Subramanyam M, Beutner U, Huber BT. 1993. Production and characterization of an Mls-1-specific monoclonal antibody. J Exp Med, vol. 177(2), 351-358. link> doi>

Chapters

  • Thompson JG, Mottershead D, Gilchrist RB. 2013. Oocyte-secreted factors in domestic animals. In Oocyte physiology and development in domestic animals. Wiley-Blackwell Publishing. doi>

I teach elements of the undergraduate curriculum for the Keele University MPharm in the School of Pharmacy.