Assistant Prof Tom Carney

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Assistant Professor Tom Carney
BSc (Hons), PhD
Assistant Professor of Developmental Biology
Email: tcarney@ntu.edu.sg
Principal Investigator, Dermal-Epidermal Interface Laboratory
Website: http://www.imcb.a-star.edu.sg/php/tc2.php

 




Laboratory Staff

  • Dr Koh Shze Yung, Research Fellow
  • Ma Jiajia, Research Assistant

 

Introduction

Dr Tom Carney is an Assistant Professor in Lee Kong Chian School of Medicine, Nanyang Technological University, and Co-Principal Investigator at the Institute of Molecular and Cell Biology (IMCB, A*STAR). Previously, he held the position of Assistant  Principal Investigator (PI) at IMCB from 2008, and was promoted to Co-PI in 2013. Before moving to Singapore, he was a postdoctoral fellow with Matthias Hammerschmidt at the Max Planck Institute for Immunobiology in Freiburg, Germany, from 2004-2008 through a Max-Planck Postdoctoral Fellowship. In 1999, he was awarded a British Council ORS Award to pursue a PhD degree under the supervision of Robert Kelsh from the Department of Biology and Biochemistry, University of Bath, UK.

Dr Carney’s research career is focused on the developmental program of derivatives of the non-neural ectoderm, namely the neural crest and the epidermis. This work has exploited the advantages of the zebrafish system for in vivo genetic and cellular analyses, and has led to publications in numerous international journals, including Current Biology, American Journal of Human Genetics, PLoS Genetics, Development, and Nature Neuroscience.

Research Focus

The Carney lab focuses on epidermal development and disease, with particular interest in the formation and signalling of the dermal-epidermal interface. The epidermis protects against external insults and infection, and thus forms a first line of defence. We are using the advantages of the zebrafish as an experimental model to analyse epidermal development and disease. The zebrafish epidermis shows high conservation with the basal-most layers of mammalian epidermis at the cellular and genetic levels (Figure 1).

Projects

  1. The skin consists of both an epithelial epidermis, comprised of keratinocytes, and a matrix-rich dermis, infiltrated by dermal fibroblasts. We have identified the source of these fibroblasts in zebrafish, and are defining their functions in maturation of the matrix and signalling to the epidermis. Furthermore, we are analysing the regulation and roles of signals, derived from the keratinocytes, have on fibroblast behaviour. We are investigating mutants that display blistering of the integument due to loss of signals between the epidermis and dermis (Figure 2).
  2. A number of human inherited diseases lead to blistering of the epidermis due to structural defects at the dermal-epidermal junction. We are currently developing models of these in the zebrafish to observe the mechanics of blister formation in vivo and in real time.
  3. Through our genetic analysis of zebrafish matrix mutants and in collaboration with human geneticists, we have identified and characterised the role of BMP1 in a type of human collagenopathy. We continue to work with human geneticists to determine the genetic basis of rare inherited diseases and develop zebrafish models to understand the underlying mechanisms.
  4. We are interested in the defensive systems of the zebrafish epidermis. We have identified that the zebrafish epidermis contains a newly described intracellular Ribonucleoprotein antibacterial defence system. We are using the powerful imaging and reverse genetics of the zebrafish to define the function and mechanism of these particles.  
Figure 1 - Striking.jpg
Figure 1: Labelling of the different layers of the adult epidermis in the zebrafish fin by a novel transgenic line
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Figure 2:      Top: Yellow fibroblasts invading the fin.
Bottom: In the absence of signalling between the epidermis and the fibroblasts, the fin fold blisters. We are studying a number of mutants with blistering in the fins.
Key Publications
1. Lee RT, Asharani PV, Carney TJ. (2014). Basal keratinocytes contribute to all strata of the adult zebrafish epidermis. PLoS One. 9: e84858.
2. Fischer B, Metzger M, Richardson R, Knyphausen P, Ramezani T, Franzen R, Schmelzer E, Bloch W, Carney TJ, Hammerschmidt M. (2014). p53 and TAp63 promote keratinocyte proliferation and differentiation in breeding tubercles of the zebrafish. PLoS Genet. 10: e1004048.
3. Lee RT, Thiery JP, Carney TJ. (2013). Dermal fin rays and scales derive from mesoderm, not neural crest. Curr Biol. 23: R336-337.
4. Lee RT, Knapik EW, Thiery JP, Carney TJ. (2013). An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchyme. Development. 140: 2923-2932.
5. Feitosa NM, Zhang J, Carney TJ, Metzger M, Korzh V, Bloch W, Hammerschmidt M. (2012). Hemicentin 2 and Fibulin 1 are required for epidermal-dermal junction formation and fin mesenchymal cell migration during zebrafish development. Dev Biol. 369: 235-248.
6. Asharani PV, Keupp K, Semler O, Wang W, Li Y, Thiele H, Yigit G, Pohl E, Becker J, Frommolt P, Sonntag C, Altmuller J, Zimmermann K, Greenspan DS, Akarsu NA, Netzer C, Schonau E, Wirth R, Hammerschmidt M, Nurnberg P, Wollnik B, Carney TJ. (2012). Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish. Am J Hum Genet. 90: 661-674.
7. Carney TJ, Feitosa NM, Sonntag C, Slanchev K, Kluger J, Kiyozumi D, Gebauer JM, Coffin Talbot J, Kimmel CB, Sekiguchi K, Wagener R, Schwarz H, Ingham PW, Hammerschmidt M. (2010). Genetic analysis of fin development in zebrafish identifies Furin and Hemicentin1 as potential novel Fraser Syndrome disease genes. PLoS Genetics. 6: e1000907.
8. Slanchev K, Carney TJ, Stemmler MP, Koschorz B, Amsterdam A, Schwarz H, Hammerschmidt M. (2009). The epithelial cell adhesion molecule EpCAM is required for epithelial morphogenesis and integrity during zebrafish epiboly and skin development. PLoS Genetics. 5: e1000563.
9. Carney TJ, von der Hardt S, Sonntag C, Amsterdam A, Topczewski J, Hopkins N, Hammerschmidt M. (2007). Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis. Development. 134: 3461-3471.
10. Carney TJ, Dutton KA, Greenhill E, Delfino-Machin M, Dufourcq P, Blader P, Kelsh RN. (2006). A direct role for Sox10 in specification of neural crest-derived sensory neurons. Development. 133: 4619-4630.