I am a developmental biologist interested in harnessing the ability of transcription factors to direct cell specification. My previous research involved all aspects of transcription factor function and regulation during body plan and organ development using model organisms (fungi, zebrafish, frogs and mice). In my current research I utilize knowledge of developmental biology to inform our reprogramming strategies to generate differentiated cells for clinical application. Currently we are applying this approach to directly reprogram liver cells to insulin expressing cells to treat diabetes and skin fibroblasts into oligodendrocyte progenitors to treat spinal cord injury. We have also developed the first transgenic mouse model to allow lineage tracing of Oct4 in both development and reprogramming. We are using this model to gain new insights into the mechanism of direct reprogramming during iPS cell generation.
Clinical application of Induced Pluripotent cells
I also direct the activities of the Cell Reprogramming Core Facility at the University of Minnesota Stem Cell Institute. My research interests here also involve the clinical application of cell reprogramming. We are working to generate Induced Pluripotent Stem (iPS) cells suitable for clinical use and use iPS cells as a pluripotent intermediate to generate specific differentiated cells for clinical transplant or modeling disease.
Selected Publications (Pubmed Search)
Ye L, Zhang S, Greder L, Dutton JR, Keirstead SA, Lepley M, Zhang L, Kaufman D, Zhang J. (2013) Effective Cardiac Myocyte Differentiation of Human Induced Pluripotent Stem Cells Requires VEGF. PLoS ONE 8(1): e53764.
Banga A, Akinci E, Greder L, Dutton JR, Slack JMW. (2012) In vivo reprogramming of Sox9 positive cells in the liver to insulin-secreting ducts. Proc Natl Acad Sci U S A. 109 (38) 15336-41
Greder L, Gupta S, Li S, Abedin M, Sajini A, Segal Y, Slack, JMW, Dutton JR. (2012) Analysis of Endogenous Oct4 Activation during iPS Cell Reprogramming Using an Inducible Oct4 Lineage Label. Stem Cells 30 (11) 2596-601
Sajini A, Greder L, Dutton JR, Slack JMW. (2012) Loss of Oct4 expression during the development of murine embryoid bodies. Developmental Biology 371, 170-179.
Kudva Y, Ohmine S, Greder L, Dutton JR, Armstrong A, De Lamo G, Khan Y, Thatava T, Hasegawa M, Fusaki N, Slack JMW, Ikeda Y. (2012) Transgene-free disease-specific induced pluripotent stem cells from patients with type 1 and type 2 diabetes. Stem Cells Translational Medicine 1 (6) 451- 461
Akinci E, Banga A, Greder LV, Dutton JR, Slack JMW. (2012) Reprogramming pancreatic exocrine cells to a beta cell character using Pdx1, Ngn3 and MafA. Biochem J. 442 (3) 539-50
Watanabe S, Hirai H, Tastad C, Verma M, Asakura Y, Keller C, Dutton JR, Asakura A. (2011) MyoD gene suppression by Oct4 is required for reprogramming in myoblasts to produce iPS cells. Stem Cells. 29 (3) 505-16
Coad RA, Dutton JR, Tosh D, Slack JMW. (2009) Inhibition of Hes1 activity in gall bladder epithelial cells promotes insulin expression and glucose responsiveness. Biochem Cell Biol. 87(6) 975-87.