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Jonathan Slack, B.A., Ph.D.
 slack017@umn.edu Biography 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 from 2007
EMBO member 1993
Waddington Medal (British Society for Developmental Biology) 2002
FMedSci 2004
Tulloch Chair in Stem Cell Biology, Genetics, and Genomics, University of Minnesota Current Research 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 hepatocytes. Current projects are being conducted both in vitro and in vivo, using viral vectors to introduce the genes. Regeneration
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, the spinal cord, and the muscle in the Xenopus tadpole tail. We are also interested in applying the technology of cell type respecification (above) to confer regenerative ability on tissues that do not normally regenerate. Selected Recent Publications since 2000:
Slack, J.M.W. (2000). Stem cells in epithelial tissues. Science287, 1431-1433.
Chalmers, A. and Slack, J.M.W. (2000). The Xenopus tadpole gut. Fate maps and morphogenetic movements. Development127, 381-392.
Shen, C.N., Slack, J.M.W. and Tosh, D. (2000). Molecular basis of transdifferentiation of pancreas to liver. Nature Cell Biology, 2, 879-887.
Slack. J.M.W. (2001). Skinny dipping for stem cells. Nature Cell Biology 3, E205-206.
Horb, M.E. and Slack, J.M.W. (2001). Endoderm Specification and Differentiation in Xenopus Embryos. Developmental Biology 236, 330-343.
Beck, C.W., Whitman, M.W. and Slack, J.M.W. (2001). The role of BMP signalling in outgrowth and patterning of the Xenopus tail bud. Developmental Biology 238, 303-314.
Tosh D. and Slack J.M.W. (2002). How cells change their phenotype. Nature Reviews Molecular Cell Biology 3, 187-194.
Tosh, D., Shen, C-N. and Slack, J.M.W. (2002). Differentiated properties of hepatocytes induced from pancreatic cells. Hepatology, 36, 534-543.
Slack, J.M.W. (2002). C.H.Waddington - the last Renaissance Biologist. Nature Reviews Genetics3, 889-895.
Horb, M.E., Shen, C.N., Tosh, D. and Slack, J.M.W. (2003). Experimental conversion of liver to pancreas. Current Biology13, 105-115.
Bennett, W.R. Crew, T.E. Slack, J.M.W. Ward A. (2003). Structural-proliferative units and organ growth: effects on insulin-like growth factor 2 on the growth of colon and skin. Development130, 1079-1088.
Beck, C. W. Christen B. and Slack J. M. W. (2003). Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate. Developmental Cell, 5, 429-439.
Slack, J.M.W. (2003). Regeneration research today. Developmental Dynamics226, 162-166.
Gargioli C.and Slack J.M.W. (2004). Cell lineage tracing during Xenopus tail regeneration. Development131, 2669-2679.
Li, W.C., Horb, M. E. , Tosh, D. and Slack, J.M.W. (2005) In vitrotransdifferentiation of hepatoma cells into functional pancreatic cells. Mechanisms of Development122, 835-847.
Yu, W.Y., Slack, J.M.W. and Tosh, D. (2005) Conversion of columnar to stratified squamous epithelium in the developing mouse oesophagus. Developmental Biology 284, 157-170.
Slack, J.M.W. (2005) Stem Cells. Entry in Encyclopaedia Britannica
Slack, J.M.W. (2005) Cell Differentiation. Entry in Encyclopaedia Britannica
Slack, J.M.W. (2006) Amphibian muscle regeneration – dedifferentiation or satellite cells ? Trends in Cell Biology16, 273-275.
Chen, Y., Lin, G. and Slack, J.M.W. (2006) Control of muscle regeneration in the Xenopus tadpole tail by Pax7. Development133, 2303-2313.
Quinlan, J.M., Yu, W.Y., Hornsey, M.A., Tosh, D. and Slack, J.M.W. (2006) In vitro culture of embryonic mouse intestinal epithelium: cell differentiation and introduction of reporter genes. BMC Developmental Biology 6: 24.
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. J. Cell Science120, 239-245.
Li, W.C., Ralphs, K. L. Slack J.M.W. and Tosh D. (2007). Keratinocyte serum free medium maintains long-term liver gene expression and function in cultured rat hepatocytes by preventing the loss of liver-enriched transcription factors. Int. J.Biochem.Cell Biol39, 541-554.
Lin, G. Chen, Y. and Slack, J.M.W. (2007). Regeneration of melanophores and other neural crest derivatives in the Xenopus tadpole tail. BMC Developmental Biology, 7:56
Thowfeequ, S., Ralphs, K., Yu, W.Y., Slack, J.M.W. and Tosh, D. (2007). Betacellulin inhibits amylase and glucagon expression and promotes beta-cell differentiation in mouse embryonic pancreas. Diabetologia 50, 1688-1697.
Slack, J.M.W. (2007). Transdifferentiation and metaplasia : from pure biology to the clinic. Nature Reviews Molecular Cell Biology8, 369-378
Slack, J.M.W. (2007). Molecular biology of the cell. Chapter 5, pp 53-66 in Principles of Tissue Engineering,ed. Lanza, R., Langer, R. and Vacanti, J.P. San Diego: Academic Press.
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. Dev. Biol.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 Sciences65, 3467 – 3480.
Slack, J.M.W. (2008). Origin of stem cells in organogenesis. Science322, 1498-1501.
Slack, J.M.W. (2009). Metaplasia and somatic cell reprogramming. J.Pathol. 217, 161–168.
Dutton, J.R., Daughters, R.S., Chen, Y., O’Neill, K.E. and Slack, J.M.W. (2009). Use of adenovirus for ectopic gene expression in Xenopus. Developmental Dynamics 238, 1412–1421.
Bosnakovski, D., Daughters, R.S., Xu, Z., Slack, J.M.W. and Kyba, M. (2009) Biphasic myopathic phenotype of mouse DUX, an ORF within conserved FSHD-related repeats. PLoS1 4, e7003.
Coad, R.A. Dutton J.R., Tosh D., Slack J. M. W. (2009) Inhibition of Hes1 activity in gall bladder epithelial cells promotes insulin expression and glucose responsiveness. Biochemistry and Cell Biology 87, 975-987.
Burke Z.D., Li W.C., Slack J.M.W., Tosh D. (2010). Isolation and culture of embryonic pancreas and liver. Methods Mol Biol. 633, 91-99. 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.
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. Biochem.J. 442, 539-550.
Slack, J.M.W. (2012). Alternative cells for regeneration. Dev. Cell 22, 689-670.
Slack, J.M.W. (2012). Stem Cells – A Very Short Introduction. Oxford University Press. Reprogramming Cells to Enable Limb Regeneration J.M.W.Slack $302,000 p.a. National Institutes of Health (NIGMS) Eureka grant, 1R01GM088500 9.1.09– 8.31.13 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 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
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