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Philip Ingham

Philip Ingham-01 (Custom).jpg

 
Professor Philip W. Ingham
FRS, FMedSci, Hon. FRCP
Toh Kian Chui Distinguished Professor and Professor of Developmental Biology  
Principal Investigator, Developmental Genetics Laboratory

 



Team

  • Dr Sowjanya Kallakuri, PhD, Research Fellow
  • Ms Kanmani Saminathan, Research Officer

 
Introduction

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. He graduated in Natural Sciences, specialising in Genetics, from the University of Cambridge in 1977 and completed research for his doctoral degree at the Univeristy of Sussex in 1980. During this time he discovered and characterised the trithorax gene in Drosophila, showing that it is a key mediator of cell memory. He did post-doctoral research in the group of Pat Simpson at the Laboratoire de Genetique Moleculaire des Eukaryotes in Strasbourg, France and subsequently in the group of David Ish-Horowicz at the Imperial Cancer Research Fund (ICRF) in London. Here he perfected the technique of visualising mRNA in embryos by in situ hybridisation, using this approach to analyse the segmentation gene hierarchy in the Drosophila embryo. He established his own independent research group at the ICRF Developmental Biology Unit in Oxford in 1986, cloning the patched and smoothened genes in Drosophila and elucidating the roles of the proteins encoded by these and other genes in the transduction of the Hedgehog signal. In 1993, in collaboration with Cliff Tabin and Andrew McMahon, his group discovered the Hedgehog family of signalling proteins in vertebrates (recognised as one of the “24 Milestones in Development” of the past century by the journal Nature in 2004) and adduced the first evidence of their role in patterning the central nervous system.  Prof Ingham has published more than 180 papers in top-ranking journals, including six “Citation Classics”.

He is an elected member of the European Molecular Biology Organisation (EMBO), a Fellow of the Royal Society as well as 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) and was President of the International Society of Developmental Biologists from 2013-2017. He is currently Head of the Developmental Biology Faculty for the online reviews journal Faculty of 1000. And serves on the External Advisory Committee of the Max-Planck Institute for Heart and Lung Research in Bad Nauheim, Germany, and the Scientific Advisory Boards of the the Sars Centre for Marine Molecular Biology in Bergen, Norway and of INOVA4 Health in Lisbon, Portugal.


Prior to joining Lee Kong Chian School of Medicine, Prof Ingham 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, Singapore.



Research Focus

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.

Selected Publications
Stainier DYR, Raz E, ... Ingham PW, et al. (2017) Guidelines for morpholino use in zebrafish.​ PLOS Genetics. 13(10):e1007000.

Gurung R, Ono Y, , ... Ingham PW. (2016). A Zebrafi​sh Model for Human Myopathy Associated with Mutation of the Unconventional Myosin MYO18B. Genetics, 205(2):725-35.

Poon KL, Wang X, ... Ingham PW, et al. (2017). Transgenic Zebrafish Reporter Lines as Alternative in vivo OrganToxicity Models, Toxicological Sciences. 156(1):133-48.

Lee RT, Ng AS, & Ingham PW (2016). Ribozyme Mediated gRNA Generation for In Vitro and In Vivo CRISPR/Cas9 Mutagenesis. PLOS One. 11(11):e0166020.

Poon KL, Wang X,... Ingham PW. (2016). Humanizing the zebrafish liver shifts drug metabolic profiles and improves pharmacokinetics of CYP3A4 substrates. Archives of Toxicology. 91(3):1187-97.

Zhao Z, Lee RT, ... Ingham PW. (2016). An essential Role for Grk2 in Hedgehog signalling downstream of Smoothened. EMBO Reports. 17:739-52.

Jackson HE, Ono Y, ... Ingham PW. (2015). The role of Sox6 in Zebrafish Muscle Fibre-Type Specification. Skeletal Muscle. 5(1):2.

Wang X, Robertson AL, ... Ingham PW. (2014). Novel natural product inhibitors of neutrophil recruitment identified through a transgenic zebrafish screen. Disease Models & Mechanisms. 7(1):163-9.

Nachtergaele S, Whalen DM, ... Ingham PW, et al. (2013). Structure and Function of the Smoothened Extracellular Domain in Vertebrate Hedgehog Signaling.​ eLIFE. 2:e0
1340.

Maurya AK, Ben J, ... Ingham PW (2013). Regulation of Gli transcription factor activity by Kif7 in the zebrafish embryo. PLOS Genetics. 9(12):e1003955.


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