Philip INGHAM    DEVELOPMENTal BIOlogy
                       
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  Philip INGHAM  
  Lab Location: #8-03

email:
pingham@imcb.a-star.edu.sg
tel:65869736
 
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  Key Publications  
 

Ingham, P.W., Taylor, A.M. & Nakano, Y. (1991)
Role of the Drosophila patched gene in positional signalling.
Nature
353: 184-187

Krauss, S., Concordet, J-P.,  and Ingham, P.W. (1993)
A Functionally Conserved Homolog of the Drosophila Segment Polarity Gene hedgehog is Expressed in Tissues with Polarising Activity in Zebrafish Embryos.
Cell 75 1431-1444

Currie, P. and Ingham, P. W. (1996)
Induction of a specific muscle cell type by a novel hedgehog gene in the zebrafish,
Nature
382: 452-455

van den Heuvel, M.,  and Ingham, P. W. (1996)
The Drosophila gene smoothened is required for hedgehog signalling and encodes a receptor-like serpentine protein.
Nature
382: 547-551

Baxendale, S., Davison, C., Muxworthy, C., Wolff, C., Ingham, P.W. and Roy, S. (2004)
The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch fiber identity in response to Hedgehog signaling.
Nature Genetics
36: 88-93

Ingham, P.W. & Placzek, M. (2006) Orchestrating ontogenesis: variations on a theme by Sonic Hedgehog. Nat Rev Genet. 7:841-50

Renshaw, SA, Loynes, CA, Trushell, DM, Elworthy, S, Ingham, PW, Whyte, MKB (2006)
A novel transgenic zebrafish model for the study of inflammation resolution. Blood, 108:3796-8

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  Philip INGHAM


Philip Ingham studied Theology, Philosophy and Genetics at Cambridge University and received his D.Phil from Sussex University, UK. He did post-doctoral research at the CNRS LGME in Strasbourg, France and at the ICRF Mill Hill laboratories in London, England, before becoming a junior Group Leader at the MRC Laboratory of Molecular Biology in Cambridge. In 1986 he was appointed Research Scientist at the ICRF Developmental Biology Unit in Oxford and became a Principal Scientist at the ICRF Lincoln’s Inn Fields Laboratories in London in 1994. In 1996 was appointed Professor of Developmental Genetics at the University of Sheffield, UK where he established the MRC Centre for Developmental and Biomedical Genetics, of which he is currently Director. He was Chairman of the British Society for Developmental Biology from 1999 to 2004 and is a member of the editorial boards of a number of leading journals including Developmental Cell, Current Biology and the EMBO Journal. He was elected a member of EMBO in 1995, a Fellow of the Academy of Medical Sciences in 2001 a Fellow of the Royal Society in 2002 and an Honorary Fellow of the Royal College of Physicians in 2007. He received the Medal of the Genetics Society of Great Britain in 2005. He joined IMCB in 2006 and was appointed Deputy Director in 2007.

     
  Developmental Biomedical Genetics
 


Hedgehog (Hh) proteins belong to one of a small number of families of secreted signals that regulate the specification, differentiation and growth of a wide variety of tissues and organs during animal development. The Ingham lab has a long-standing interest in the mechanistic basis of Hedgehog (Hh) pathway signalling and how it controls cell fates. We pioneered the genetic analysis of the signalling pathway in Drosophila, identifying the Hh receptor, Patched, and transmembrane transducer, Smoothened as well as elucidating the roles of the Fused, Costal-2 and Ci proteins in the intracellular transduction of the signal. In collaboration with Andy McMahon and Cliff Tabin, we identified the vertebrate homologues of Hh and showed that one of these, Sonic hedgehog (Shh) is expressed in a number of crucial organizing centres, notably the Zone of polarizing activity, notochord and floor plate.

Subsequent studies have focused on the role of Hh signalling in the specification of muscle cell identity in the zebrafish. We demonstrated that different populations of muscle fibers are specified in response to different levels of Hh signaling, and identified the transcription factor Prdm1 as a key target of Hh signaling in this process.

One focus of our current research is to understand the basis of the differential response of cells to Hh signaling in the zebrafish and to characterize the divergence in the Hh signaling pathway between Drosophila, teleosts and mammals. We use a variety of approaches, including transgenesis, in vivo imaging of pathway components and proteomic analysis of signaling complexes.
We also continue to study the transcriptional networks underlying the specification and differentiation of skeletal muscle in the zerbafish, using Chromatin immuno precipitation (ChIP) together with forward and reverse genetics.

A second major theme in our lab is the analysis of disease related processes using the zebrafish as a model system. In collaboration with clinician scientists in the UK we have established models of the inflammatory response and arteriogenesis and are using these as the basis for chemical genetic screens. We are also using establishing xenograft models in the zebrafish to study tumor angiogenesis.

     
     
   
         
 
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