Jonathan Slack, M.A., Ph.D.
B.A. Biochemistry (Oxon) 1971
Ph.D. (Edinburgh) 1974
Postdoc, Middlesex Hospital Medical School, London 1974-76
Staff Scientist, Imperial Cancer Research Fund 1976-95
(at Mill Hill Institute and later Developmental Biology Unit, Oxford)
Professor of Developmental Biology, University of Bath, from 1995
Head of Department of Biology & Biochemistry, University of Bath 2000-2006
Director, Stem Cell Institute, University of Minnesota 2007-2012
EMBO member 1993
Waddington Medal (British Society for Developmental Biology) 2002
FMedSci (Academy of Medical Sciences, UK) 2004
Tulloch Chair in Stem Cell Biology, Genetics, and Genomics, University of Minnesota
Respecification of cell type
Different cell types can sometimes be interconverted by introduction of genes for the appropriate transcription factors. The transcription factors that are effective are those that control formation of the relevant tissues and cell types during normal embryonic development. The ability to make induced pluripotent stem cells (iPS cells) is a particularly spectacular example of this principle, but many other transformations are possible that do not involve a complete reversion to pluripotent behavior.
We are interested in possible therapeutic applications of this technique, especially in relation to the production of pancreatic beta cells from developmentally related cell types such as progenitor cells found in the liver. Current projects are being conducted both in vitro and in vivo, using viral vectors to introduce the genes.
Some animals are able to regenerate missing parts. Among these are the tadpoles which represent the juvenile stage of frog development. Understanding the cellular and molecular mechanisms of these regeneration processes could have important implications for human health. We are presently studying the mechanisms of regeneration of the limbs in the frog Xenopus. We find that limb regeneration can be provoked by a graft of larval limb bud cells together with suitable factors.
Selected Recent Publications
Slack, J.M.W. (2012). Stem Cells: A Very Short Introduction. Oxford University Press.
Slack, J.M.W. (2012). Essential Developmental Biology, third edition. Wiley-Blackwell.
Selected Recent Papers:
Dutton, J.R., Chillingworth, N.L., Brannon, C.A., Eberhard, D., Hornsey, M., Tosh, D and Slack, J.M.W. (2007). Beta cells occur naturally in extrahepatic bile ducts of mice. J. Cell Science120, 239-245.
Slack, J.M.W. (2007). Transdifferentiation and metaplasia : from pure biology to the clinic. Nature Reviews Molecular Cell Biology 8, 369-378
Slack, J.M.W., Lin, G and Chen, Y. (2008). The Xenopus tadpole, a new model for regeneration research. Cellular and Molecular Life Sciences 65, 54-63.
Lin, G. and Slack, J.M.W. (2008). Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration. Developmental Biology 316, 323-335.
Eberhard, D., Tosh, D., and Slack J.M.W. (2008). Origin of pancreatic endocrine cells from biliary duct epithelium. Cellular and Molecular Life Sciences 65, 3467 – 3480.
Slack, J.M.W. (2008). Origin of stem cells in organogenesis. Science 322, 1498-1501.
Daughters, R.S., Chen, Y. and Slack, J.M.W. (2011). Origin of muscle satellite cells in the Xenopus embryo. Development 138, 821-830.
Slack, J.M.W. (2011). Planarian Pluripotency. Science 332, 799-800.
Slack, J.M.W. (2012). Alternative cells for regeneration. Developmental Cell 22, 689-670.
Akinci, E., Banga, A., Greder, L.V., Dutton, J.R. and Slack, J.M.W. (2012). Reprogramming of pancreatic exocrine cells towards a beta cell character using Pdx1, Ngn3 and MafA. Biochemical Journal 442, 539-550.
Banga, A., Akinci, E., Greder, L.V., Dutton, J.R., and Slack, J.M.W. (2012). In vivo reprogramming of Sox9 positive cells in the liver to insulin-secreting ducts. Proceedings of the National Academy of Sciences USA 109, 15336-15341.
Sajini, A.A., Greder, L.V., Dutton, J.R., and Slack, J.M.W. (2012). Loss of Oct4 expression during the development of murine embryoid bodies. Developmental Biology 371, 170-179.
Greder, L.V., Gupta, S., Li, S., Abedin, M.J., Sajini, A., Segal, Y, Slack, J.M.W. and Dutton, J.R. (2012). Analysis of endogenous Oct4 activation during iPS cell reprogramming using an inducible Oct4 lineage label. Stem Cells 30, 2596-2601.
Reprogramming Cells to Enable Limb Regeneration
$302,000 p.a. National Institutes of Health (NIGMS) Eureka grant, 1R01GM088500
Midwestern Progenitor Cell Consortium
MPI: D.J.Garry; Co-PIs: D.A.Taylor, M.Kyba, J.Zhang, D.S.Kaufman, J.M.W.Slack
$1,132,500 p.a. National Institutes of Health (NHLBI) 1U01HL100407
9.30.2009 – 6.30.2016
Making Beta Cells from Hepatocytes
J. M.W. Slack
$377,500 p.a. National Institutes of Health (NIDDK) 1R01DK080747
04/01/2010 – 02/28/2015
Stem Cell Biology Training Program
D.S.Kaufman (P.I.) J.M.W.Slack (CoI)
$175,802 p.a. National Institutes of Health (NICHD) Training grant. T32HD060536
08/15/10 - 07/31/15
Novel Tissue Engineering of Patient-Specific Islet Cells for Diabetes Therapy.
J.M.W.Slack and Y.Ikeda (Mayo Clinic) (Co-P.I.s)
$648,645 total. Minnesota Partnership for Biotechnology and Medical Genomics
02/01/11 - 01/31/13
Generation of Cardiomyocytes from Muscle Satellite Cells of the Head
J.M.W.Slack and R.S.Daughters
$151,000 p.a. University of Maryland. SR00002157
Subcontract from NHLBI U01HL099997 Progenitor Cell Biology Consortium Coordination Core.
03/01/12 - 02/28/14