Professor Philip Ingham, FRS, FMedSci, Hon. FRCP
Professor of Developmental Biology
Principal Investigator, Zebrafish Models of Human Disease Laboratory
- Dr Sowjanya Kallakuri, PhD, Research Fellow
- Dr Yin Juan, PhD, Research Fellow
- Dr Yosuke Ono, PhD, Research Fellow
Professor Philip Ingham is Professor
of Developmental Biology at Lee Kong Chian School of Medicine, Nanyang
Technological University as well as Director of the Living Systems Institute at
the University of Exeter, UK. Previously, he was founding Director of the MRC
Centre for Developmental & Biomedical Genetics at the University of
Sheffield, UK, and Deputy Director of the A*STAR Institute of Molecular and
Cell Biology. After graduating from the Universities of Cambridge and Sussex in
the UK, he spent ten years as a Principal Investigator first at the MRC
Laboratory of Molecular Biology in Cambridge and then at Imperial Cancer Research Fund (now CRUK)
Laboratories in Oxford and London.
Internationally recognised for
his contributions to the developmental genetics of both Drosophila and
zebrafish, Prof Ingham has published more than 170 papers in top-ranking
journals, including four “Citation Classics”. His research has provided
fundamental insights into cell signalling in the developing embryo and has
relevance both to regenerative medicine and cancer biology. He elucidated the
Hedgehog signalling pathway in Drosophila and cloned and characterised the
Sonic hedgehog gene in vertebrates, a discovery recognised as one of the 24 Milestones in Development of the past century by the
journal Nature in 2004.
Prof Ingham is a Fellow of the Royal
Society and of the UK Academy of Medical Sciences and an Honorary Fellow of the
Royal College of Physicians. He was awarded the Genetics Society Medal in 2005
and the Waddington Medal, the only national award in
developmental biology in the UK, in 2014.
Prof Ingham has served on
the advisory panels of a number of international funding bodies including the
Research Grants Council of the Hong Kong University Grants Committee, the
European Molecular Biology Organisation (EMBO), the Wellcome Trust and the Human
Frontiers of Science Programme (HFSP). He is Head of the Developmental Biology
Faculty for the online reviews journal Faculty of 1000 and President of the
International Society of Developmental Biologists. He currently serves on the
External Advisory Committee of the Max-Planck Institute for Heart and Lung
Research in Bad Nauheim, Germany, and the Scientific Advisory Board of the Sars
Centre for Marine Molecular Biology in Bergen, Norway.
Research in Prof Ingham’s lab aims
to understand complex biological processes in the context of the whole
organism. The lab uses genetically tractable model organisms, principally the
tropical fish Danio rerio (commonly known as the zebrafish), in their research.
Zebrafish not only offer exceptional opportunities for in vivo imaging, genetic
manipulation analysis and high throughput drug screening, but also address the
aims of the 3Rs – Reduction, Refinement, Replacement - in animal research.
Intercellular Singnalling by Hedgehog Family Proteins
The lab’s long-standing interest in the Hedgehog (Hh) signalling pathway is of direct relevance to human disease. Hh proteins control a variety of processes, both during embryonic development as well as post-embryonically, for instance in tissue homeostasis and physiological processes such as pain perception and glucose metabolism. Not surprisingly, dysfunction of the Hh pathway underlies many clinical conditions. We aim to understand the complexities of Hh signalling through the in vivo functional analysis of its various components, using the zebrafish as a model. The knowledge generated in this way will continue to contribute to the development of novel therapeutics for cancer, algesia and metabolic disorders.
Myogenesis and Muscle Disease
Skeletal muscle is a major component of vertebrate anatomy, making up around 50% of the body mass of a human and around 80% of that of a fish. We exploit the many advantages of the zebrafish to analyse in vivo the specification, differentiation and function of skeletal muscle cells. One focus is on the specification of the physiologically distinct muscle cell fibre-types: we have elucidated a regulatory network that integrates the activities of signaling factors, transcription factors and micro RNAs (miRs) in the specification of slow-twitch muscle fibres in the developing embryo. A second focus is on the control of muscle fibre differentiation: we have uncovered a role in sarcomere assembly for an unconventional, mutations of which are associated with nemaline myopathies in human. Together, these studies illustrate the power of the zebrafish as a model system for understanding the mechanistic basis of human myopathies and for uncovering the pathways of specification that can be exploited in regenerative medicine.
- Gurung R, Ono Y, Baxendale S, Lee SL, Moore S,
Calvert M, Ingham PW. (2016) A Zebrafish Model for Human Myopathy
Associated with Mutation of the Unconventional Myosin MYO18B. Genetics.
- Lee RT, Ng AS, Ingham PW. (2016) Ribozyme Mediated gRNA Generation
for In Vitro and In Vivo CRISPR/Cas9 Mutagenesis. PLoS One.
- Poon KL, Wang X, Ng AS, Goh WH, McGinnis C, Fowler S, Carney TJ, Wang H, Ingham
PW. (2106) Humanizing the zebrafish liver shifts drug metabolic profiles
and improves pharmacokinetics of CYP3A4 substrates. Arch Toxicol. PMID:
- Zhao Z, Lee RT,
Pusapati, GV Iyu, AQ. Rohatgi R, Ingham,
PW (2016) An essential Role for Grk2 in Hedgehog signalling downstream of
Smoothened. EMBO Reports ;17(5):739-52.
- Leow SC, Poschmann J, Too PG,
Yin J, Joseph R, McFarlane C, Dogra S, Shabbir A, Ingham PW, Prabhakar S, Leow MK, Lee YS, Ng KL, Chong YS, Gluckman
PD, Stünkel W (2016) The transcription factor SOX6 contributes to the
developmental origins of obesity by promoting adipogenesis. Development 143(6):950-61.
- Ono Y, Yu W, Jackson HE,
Parkin CA, Ingham PW (2015) Adaxial
cell migration in the zebrafish embryo is an active cell autonomous property
that requires the Prdm1a transcription factor. Differentiation. 89(3-4):77-86.
- Jackson, H.E., Ono, Y., Wang,
X., Elworthy, S., Cunliffe, V.T. Ingham,
P.W. (2015) The role of Sox6 in Zebrafish Muscle Fibre-Type
Specification. Skeletal Muscle, 5(1)2 doi:
- Wang X, Robertson AL, Li
J, Chai RJ, Haishan W, Sadiku P, Ogryzko NV, Everett M, Yoganathan K, Luo HR,
Renshaw SA, Ingham PW. (2014) Novel
natural product inhibitors of neutrophil recruitment identified through a
transgenic zebrafish screen. Dis Model Mech.
- Nachtergaele, S. Whalen,
DM. Mydock, L. Zhao, Z. Malinauskas, T. Ingham,
PW. Covey, DF. Siebold, C. and Rohatgi, R. (2013) Structure and Function of
the Smoothened Extracellular Domain in Vertebrate Hedgehog Signaling. eLIFE. Oct 29;2:e01340. doi: 10.7554/eLife.01340.
- Maurya AK, Ben J, Zhao
Z, Lee RT, Niah W, Ng AS, Iyu A, Yu W, Elworthy S, van Eeden FJ, Ingham PW. (2013) Regulation of Gli
transcription factor activity by Kif7 in the zebrafish embryo. PLoS Genet. 9(12):e1003955