Executive Dean of The Faculty of Creative Arts, Technologies & Science

I gained my PhD through a series of biochemical studies on a then novel neuropeptide termed neuromedin U. I was the first in the world to quantify the expression of this peptide and document its tissue distribution.

I then moved to the Imperial Cancer Research Fund where under the guidance of Dr Enrique Rozengurt I began my interest in how phospholipids regulate the proliferation of cells in response to growth factor stimulation. I continued my training focusing my efforts on the recently cloned phosphoinositide 3-kinase (PI3K) enzyme in the laboratory of Professor Michael Waterfield FRS at the Ludwig Institute.

There I was the first to clone a series of genes that encode PI3K enzymes and their adaptor proteins including the first class II PI3K enzyme termed Drosophila 68_D.

I was the first to describe a human class II PI3K enzyme termed PI3K-C2alpha. In 1998 I left to establish an independent research group accepting the position of Lecturer at Imperial College.

Since that time my research efforts have focused on the human class II PI3K enzymes. I have demonstrated that they act downstream of several cell surface receptors and serve to regulate growth factor induced changes in intracellular vesicle transport and migration.

I have ongoing projects that focus on growth factor induced migration of breast cancer cells and novel mechanisms that occur in renal cancer cells in response to nutrient deprivation.

In addition I am investigating the hypothesis that the receptor for nerve growth factor binds connective tissue growth factor (CTGF) to elicit the synthesis of extracellular matrix proteins in renal cells.

Qualifications

• PhD in Biochemistry, University of London, Royal Postgraduate Medical School

Research plans

Prominent in my future research plans is the analysis of class II PI3K enzyme null-mice that we have either re-derived (PI3K-C2beta) or will shortly receive from my collaborator Dr Tamas Oravecz, Lexicon Pharmaceuticals, Inc USA (PI3K-C2alpha and PI3K-C2gamma).

I wish to build on the foundations I have established at the Ludwig Institute and Imperial College that will allow me to improve our understanding of growth factor receptor stimulated proliferation and migration of tumour cells through phosphoinositide signalling.

Recent Research Volume

BBRSC £ 36,710
Jan Domin and Professor Yuri Korchev
Underwood Fellowship
March 2006-Feb 2007

MRC £210,434
Jan Domin
Project Grant Nov 2006- Oct 2009
“Regulation of cell morphology, migration and adhesion by class II phosphoinositide 3-kinase enzymes”

Regione Autonoma Della Sardegna €61,730
Master and Back Pre-doctoral scholarship awarded to Simona Deplano
Nov 2007 – Oct 2009 (support extended to Oct 2010)
Supervisor Jan Domin

Diabetes UK £206,181
Prof R Mason, Dr Jan Domin, Dr George Bou-Gharios
Project Grant Sept 2008- Aug 2011
“The interaction of connective tissue growth factor with neurotrophin receptors – a possible therapeutic target in diabetic nephropathy”

The Wellcome Trust £ to be confirmed
Pre-doctoral Fellowship awarded to Emma Salisbury
Sept 2009-Aug 2012
Supervisors Professor Philip Ashton-Rickardt and Jan Domin

Myotubular Trust £38,548
Richard Piercy, Susan Brown, Jan Domin Cesare Terracciano
Project Grant Oct 2009-Sept 2012
“The Role of PTPLA in Canine Centronuclear Myopathy”

Selected guest lectures

• 2005 Site visit and 2 lectures - Nencki Institute of Experimental Biology, Warsaw, Poland
• 2006 Biochemistry Dept, University of Reading, UK
• 2007 Keynote presentation at Keystone Meeting “PI3K Signalling Pathways in Disease”
• Santa Fe, New Mexico USA
• 2007 Division of Clinical Pharmacology, NYU Medical Centre, USA
• 2007 Department of Biochemistry, Monash University Melbourne, Australia
• 2008 MRC Centre for Inflammation Research, Edinburgh UK
• 2009 Department of Pharmacology, University of Illinois at Chicago, USA

Recent awards

• 2008 Nominated by the Division of Medicine for the Imperial Award for Teaching.
• 2009 Rectors Award – Commendation - Excellence in Pastoral Care

Professional memberships

• The Biochemical Society
• The Renal Association
• The American Society for Cell Biology

Publications

2 book chapters, 64 original publications

Book Chapters

• Phosphoinositide 3-kinase enzymes as downstream targets of the EGF receptor Domin J in Epidermal Growth Factor Signalling Networks in Cancer Therapy. Humana Press 2009 Gullick W and Halley J ed.
• Phosphoinostide signalling pathways Domin J in Phosphoinositide 3-kinase signalling pathway: The key to cell proliferation and death Imperial College Press 2006 Lam E F-W ed.

Original Articles

• Banfic H, Visnjic D, Mise N, Balakrishnan S, Depano S, Korchev Y and Domin J (2009) “Epidermal growth factor stimulates translocation of the class II phosphoinositide 3-kinase PI3K-C2beta to the nucleus.” Biochem J 422, 53-60
• Wen PJ, Osborne SL, Morrow IC, Parton RG, Domin J, Meunier FA (2008) “Ca2+-regulated Pool of PtdIns(3)P Produced by PI3 kinase-C2{alpha} on Neurosecretory Vesicles.” Mol Biol Cell.19, 5593-603
• El Sheikh SS, Romanska HM, Abel P, Domin J, Lalani el-N (2008) “Predictive value of PTEN and AR coexpression of sustained responsiveness to hormonal therapy in prostate cancer--a pilot study”. Neoplasia 10, 949-53
• Behmoaras J, Bhangal G, Smith J, McDonald K, Mutch B, Lai PC, Domin J, Game L, Salama A, Foxwell BM, Pusey CD, Cook HT, Aitman TJ.(2008) “Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility “.Nat Genet. 40, 553-9.
• Marchbank T, Mahmood A, Fitzgerald AJ, Domin J, Butler M, Goodlad RA, Elia G, Cox HM, van Heel DA, Ghosh S, Playford RJ (2007) “Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents.” Am J Pathol 171, 1462-73.
• Das, M., Scappini E., Martin, NP., Wong, KA., Dunn ,S. Chen, YJ., Miller SL, Domin, J and O’Bryan, JP (2007) “Regulation of Neuron Survival Through an Intersectin (ITSN)-Phosphatidylinositol 3’-Kinase Class IIβ-AKT Pathway.” Mol Cell Biol. 27, 7906-17
• Harper L., Kashiwagi Y., Pusey CD., Hendry BM., Domin J. (2007) “PDGF re-organizes the actin cytoskeleton through phosphoinositide 3-kinase dependent and independent mechanisms in human mesangial cells.” Nephron Physiol. 107, 45-56
• Aitman, TJ; Dong, R; Vyse, TJ; Norsworthy, PJ; Johnson, MD; Smith J; Mangion, J; Roberton-Lowe, CR; Marshall, AJ; Petretto, E; Hodges, MD; Bhangal, G; Patel, SG; Sheehan, KS; Duda, M; Cook, PR; Evans DJ; Domin, J; Flint, J; Boyle, JJ, Pusey, CD and Cook, HT (2006) “Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans.” Nature 439; :851-5
• Wheeler M; Domin J; (2006) "The N-terminus of phosphoinositide 3-kinase-C2beta regulates lipid kinase activity and binding to clathrin." J Cell Physiol 206: 586-93
• Taylor JR; Brownlow N; Domin J; Dibb NJ; (2006) "FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance." Oncogene 5:147-51
• Domin J; Harper L; Aubyn D; Wheeler M; Florey O; Haskard D; Yuan M; Zicha D; (2005) "The class II phosphoinositide 3-kinase PI3K-C2beta regulates cell migration by a PtdIns(3)P dependent mechanism." J Cell Physiol 205, 452-62
• Meunier FA; Osborne SL; Hammond GR; Cooke FT; Parker PJ; Domin J; Schiavo G; (2005) "Phosphatidylinositol 3-Kinase C2{alpha} Is Essential for ATP-dependent Priming of Neurosecretory Granule Exocytosis." Mol Biol Cell 16, 4841-51
• El Sheikh SS; Domin J; Abel P; Stamp G; Lalani el-N; (2004) "Phosphorylation of both EGFR and ErbB2 is a reliable predictor of prostate cancer cell proliferation in response to EGF." Neoplasia 6, 846-53
• El Sheikh SS; Domin J; Tomtitchong P; Abel P; Stamp G; Lalani EN; (2003) "Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation." BMC Clin Pathol 3, 4
• El Sheikh SS; Domin J; Abel P; Stamp G; Lalani el-N; (2003) "Androgen-independent prostate cancer: potential role of androgen and ErbB receptor signal transduction crosstalk." Neoplasia 5, 99-109
• Nishino T; Pusey CD; Domin J; (2002) "Elevated Akt phosphorylation as an indicator of renal tubular epithelial cell stress." J Biol Chem volume 277, 33943-9
• Wheeler M; Domin J; (2001) "Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2." Mol Cell Biol 21, 6660-7
• Gaidarov I; Smith ME; Domin J; Keen JH; (2001) "The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking." Mol Cell 7, 443-9
• Row PE; Reaves BJ; Domin J; Luzio JP; Davidson HW; (2001) "Overexpression of a rat kinase-deficient phosphoinositide 3-kinase, Vps34p, inhibits cathepsin D maturation." Biochem J 353, 655-61
• Arcaro A; Zvelebil MJ; Wallasch C; Ullrich A; Waterfield MD; Domin J; (2000) "Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors." Mol Cell Biol 20, 3817-30
• Domin J; Gaidarov I; Smith ME; Keen JH; Waterfield MD; (2000) "The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles." J Biol Chem 275, 11943-50
• Brown RA; Domin J; Arcaro A; Waterfield MD; Shepherd PR; (1999) "Insulin activates the alpha isoform of class II phosphoinositide 3-kinase." J Biol Chem 274, 14529-32
• Turner SJ; Domin J; Waterfield MD; Ward SG; Westwick J; (1998) "The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/p110 phosphatidylinositol 3-kinase and the class II PI3K-C2alpha." J Biol Chem 273, 25987-95
• Domin J; Pages F; Volinia S; Rittenhouse SE; Zvelebil MJ; Stein RC; Waterfield MD; (1997) "Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin." Biochem J 326, 139-47
• Domin J; Waterfield MD; (1997) "Using structure to define the function of phosphoinositide 3-kinase family members." FEBS Lett 410, 91-5
• Linassier C; MacDougall LK; Domin J; Waterfield MD; (1997) "Molecular cloning and biochemical characterization of a Drosophila phosphatidylinositol-specific phosphoinositide 3-kinase." Biochem J 321, 849-56
• Panaretou C; Domin J; Cockcroft S; Waterfield MD; (1997) "Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex." J Biol Chem 272, 2477-85
• Domin J; Dhand R; Waterfield MD; (1996) "Binding to the platelet-derived growth factor receptor transiently activates the p85alpha-p110alpha phosphoinositide 3-kinase complex in vivo." J Biol Chem 271, 21614-21
• Zvelebil MJ; MacDougall L; Leevers S; Volinia S; Vanhaesebroeck B; Gout I; Panayotou G; Domin J; Stein R; Pages F; (1996) "Structural and functional diversity of phosphoinositide 3-kinases." Philos Trans R Soc Lond B Biol Sci 351, 217-23
• MacDougall LK; Domin J; Waterfield MD; (1995) "A family of phosphoinositide 3-kinases in Drosophila identifies a new mediator of signal transduction." Curr Biol 5, 1404-15
• Volinia S; Dhand R; Vanhaesebroeck B; MacDougall LK; Stein R; Zvelebil MJ; Domin J; Panaretou C; Waterfield MD; (1995) "A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system." EMBO J 14, 3339-48
• Domin J; Higgins T; Rozengurt E; (1994) "Preferential inhibition of platelet-derived growth factor-stimulated DNA synthesis and protein tyrosine phosphorylation by nordihydroguaiaretic acid." J Biol Chem 269, 8260-7
• Domin J; Rozengurt E; (1993) "Platelet-derived growth factor stimulates a biphasic mobilization of arachidonic acid in Swiss 3T3 cells. The role of phospholipase A2." J Biol Chem 268, 8927-34
• Playford RJ; Benito-Orfila MA; Nihoyannopoulos P; Nandha KA; Cockcroft J; Todd S; Ghatei MA; Domin J; Bloom SR; Calam J; (1992) "Effects of peptide YY on the human cardiovascular system: reversal of responses to vasoactive intestinal peptide." Am J Physiol 263, E740-7
• Domin J; Benito-Orfila MA; Nandha KA; Aitken A; Bloom SR; (1992) "The purification and sequence analysis of an avian neuromedin U." Regul Pept 41, 1-8
• Domin J; Rozengurt E; (1992) "Heterologous desensitization of platelet-derived growth factor-mediated arachidonic acid release and prostaglandin synthesis." J Biol Chem 267, 15217-23
• Kreymann B; Ghatei MA; Domin J; Kanse S; Bloom SR; (1991) "Developmental patterns of glucagon-like peptide-1-(7-36) amide and peptide-YY in rat pancreas and gut." Endocrinology 129, 1001-5
• Benito-Orfila MA; Domin J; Nandha KA; Bloom SR; (1991) "The motor effect of neuromedin U on rat stomach in vitro."
• Eur J Pharmacol 193, 329-33
• Jones PM; O'Halloran DJ; Ghatei MA; Domin J; Bloom SR; (1990) "The influence of adrenal hormone status on neuroendocrine peptides in the rat anterior pituitary gland." J Endocrinol 127, 437-44
• O'Halloran DJ; Jones PM; Ghatei MA; Domin J; Bloom SR; (1990) "The regulation of neuropeptide expression in rat anterior pituitary following chronic manipulation of estrogen status: a comparison between substance P, neuropeptide Y, neurotensin, and vasoactive intestinal peptide." Endocrinology 127, 1463-9
• Williams G; Cardoso HM; Domin J; Ghatei MA; Russell JC; Bloom SR; (1990) "Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat." Diabetes Res 15, 1-7
• Playford RJ; Domin J; Beacham J; Parmar KB; Tatemoto K; Bloom SR; Calam J; (1990) "Preliminary report: role of peptide YY in defence against diarrhoea." Lancet 335, 1555-7
• Nicholls J; Wynick D; Domin J; Sandler LM; Bloom SR; (1990) "Pharmacokinetics of the long-acting somatostatin analogue octreotide (SMS 201-995) in acromegaly." Clin Endocrinol (Oxf) 32, 545-50
• Domin J; Al-Madani AM; Desperbasques M; Bishop AE; Polak JM; Bloom SR; (1990) "Neuromedin U-like immunoreactivity in the thyroid gland of the rat." Cell Tissue Res 260, 131-5
• Spokes RA; Lee YC; Yiangou Y; Domin J; Bloom SR; (1990) "Comparison of neuromedin-N and neurotensin on net fluid flux across rat small intestine." Eur J Pharmacol 175, 43-7
• Goodlad RA; Ghatei MA; Domin J; Bloom SR; Wright NA; (1990) "Is peptide YY trophic to the intestinal epithelium of parenterally fed rats?" Digestion 46, 177-81
• Domin J; Yiangou YG; Spokes RA; Aitken A; Parmar KB; Chrysanthou BJ; Bloom SR; (1989) "The distribution, purification, and pharmacological action of an amphibian neuromedin U." J Biol Chem 264, 20881-5
• Beardshall K; Frost G; Morarji Y; Domin J; Bloom SR; Calam J; (1989) "Saturation of fat and cholecystokinin release: implications for pancreatic carcinogenesis." Lancet 2, 8670, 1008-10
• Domin J; Steel JH; Adolphus N; Burrin JM; Leonhardt U; Polak JM; Bloom SR; (1989) "The anterior pituitary content of neuromedin U-like immunoreactivity is altered by thyrotrophin-releasing hormone and thyroid hormone status in the rat." J Endocrinol 122, 471-6
• Calam J; Ghatei MA; Domin J; Adrian TE; Myszor M; Gupta S; Tait C; Bloom SR; (1989) "Regional differences in concentrations of regulatory peptides in human colon mucosal biopsy." Dig Dis Sci 34, 1193-8
• Goodlad RA; Ratcliffe B; Fordham JP; Ghatei MA; Domin J; Bloom SR; Wright NA; (1989) "Plasma enteroglucagon, gastrin and peptide YY in conventional and germ-free rats refed with a fibre-free or fibre-supplemented diet." Q J Exp Physiol 74, 437-42
• Nikou GC; Yiangou Y; Chrysanthou BJ; Domin J; Bloom SR; (1989) "Peptide histidine valine-42 stimulates gastric acid secretion in man." Biosci Rep 9, 369-74
• Green DM; Bishop AE; Rindi G; Lee FI; Daly MJ; Domin J; Bloom SR; Polak JM; (1989) "Enterochromaffin-like cell populations in human fundic mucosa: quantitative studies of their variations with age, sex, and plasma gastrin levels." J Pathol 157, 235-41
• Goodlad RA; Ghatei MA; Domin J; Bloom SR; Gregory H; Wright NA; (1989) "Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?" Experientia 45, 168-9
• Gill JS; Ghatei MA; Domin J; Bloom SR; (1989) "The generation of valosin-like peptides from a precursor protein in vitro as an extraction artifact." Life Sci 44, 483-91
• Conlon JM; Domin J; Thim L; DiMarzo V; Morris HR; Bloom SR; (1988) "Primary structure of neuromedin U from the rat." J Neurochem 51, 988-91
• Ballesta J; Carlei F; Bishop AE; Steel JH; Gibson SJ; Fahey M; Hennessey R; Domin J; Bloom SR; Polak JM; (1988) "Occurrence and developmental pattern of neuromedin U-immunoreactive nerves in the gastrointestinal tract and brain of the rat." Neuroscience 25, 797-816
• Davis TM; Bray G; Domin J; Bloom SR; (1988) "A case of somatostatinoma: responses to food and SMS 201-995 administration." Pancreas 3, 729-33
• Domin J; Polak JM; Bloom SR; (1988) "The distribution and biological effects of neuromedins B and U." Ann N Y Acad Sci 547, 391-403
• Steel JH; Van Noorden S; Ballesta J; Gibson SJ; Ghatei MA; Burrin J; Leonhardt U; Domin J; Bloom SR; Polak JM; (1988) "Localization of 7B2, neuromedin B, and neuromedin U in specific cell types of rat, mouse, and human pituitary, in rat hypothalamus, and in 30 human pituitary and extrapituitary tumors." Endocrinology 22, 270-82
• Domin J; Ghatei MA; Chohan P; Bloom SR; (1987) "Neuromedin U - a study of its distribution in the rat." Peptides 8, 779-84
• Fuessl HS; Domin J; Bloom SR; (1987) "Oral absorption of the somatostatin analogue SMS 201-995: theoretical and practical implications." Clin Sci (Lond) 72, 255-7
• Fuessl HS; Domin J; Anderson JV; Bloom SR; (1987) "Chronic administration of the somatostatin analogue SMS 201-995 does not lead to endogenous antibody formation." Aliment Pharmacol Ther 1, 45-50
• Adrian TE; Domin J; Bacarese-Hamilton AJ; Bloom SR; (1986) "Is the C-terminal flanking peptide of rat cholecystokinin double sulphated?" FEBS Lett 196, 5-8

Contact details

T: +44 (0)1582 489134
E: jan.domin@beds.ac.uk