Harvard University - Department of Molecular & Cellular Biology

KEVIN EGGAN

Eggan
Professor of Stem Cell and Regenerative Biology

Email: keggan@scrb.harvard.edu
Phone: 617-496-5611

Mail: SF 258A
Sherman Fairchild
7 Divinity Ave
Cambridge, MA  02138

Eggan Lab Homepage
Members of the Eggan Lab
List of Publications from PubMed

Research

A fundamental understanding of how a cell's identity is determined during differentiation and how it can in turn be manipulated experimentally is a central goal of developmental biology, one with substantial ramifications for biomedicine. We study both the differentiation of embryonic stem cells into the neural lineage and the reprogramming of commonly available differentiated cell types, such as fibroblasts, into either pluripotent stem cells or cells of therapeutic interest, such as spinal motor neurons. To study differentiation and dedifferentiation, we employ a variety of approaches, including stem cell differentiation, nuclear transfer, and defined reprogramming strategies using known transcriptional regulators and novel small-molecule compounds.

A number of devastating diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), specifically affect the neuromuscular system. Little is known concerning the molecular pathology underlying these conditions, partly because it has been impossible to access significant quantities of the disease-affected cell, the spinal motor neuron. With recent advances in stem cell and reprogramming biology, we can now produce billions of spinal motor neurons with control and diseased genotypes. We use this new resource to design in vitro disease models for both mechanistic studies and for the discovery of novel small-molecule therapeutics.

Publications

Williams LA, Davis-Dusenbery BN, Eggan KC. SnapShot: directed differentiation of pluripotent stem cells. Cell 2012 May;149(5):1174–1174.e1. PubMed

Mekhoubad S, Bock C, de Boer AS, Kiskinis E, Meissner A, Eggan K. Erosion of dosage compensation impacts human iPSC disease modeling. Cell stem cell 2012 May;10(5):595–609. PubMed

Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, Gnirke A, Eggan K, Meissner A. Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 2011 Feb;144(3):439–52. PubMed

Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, Eggan K. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell stem cell 2011 Sep;9(3):205–18. PubMed

Egli D, Chen AE, Saphier G, Powers D, Alper M, Katz K, Berger B, Goland R, Leibel RL, Melton DA, Eggan K. Impracticality of egg donor recruitment in the absence of compensation. Cell stem cell 2011 Oct;9(4):293–4. PubMed

Gore A, Li Z, Fung H-L, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee J-H, Loh Y-H, Manos PD, Montserrat N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Izpisua Belmonte JC, Rossi DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LSB, Zhang K. Somatic coding mutations in human induced pluripotent stem cells. Nature 2011 Mar;471(7336):63–7. PubMed

Boulting GL, Kiskinis E, Croft GF, Amoroso MW, Oakley DH, Wainger BJ, Williams DJ, Kahler DJ, Yamaki M, Davidow L, Rodolfa CT, Dimos JT, Mikkilineni S, MacDermott AB, Woolf CJ, Henderson CE, Wichterle H, Eggan K. A functionally characterized test set of human induced pluripotent stem cells. Nature biotechnology 2011 Mar;29(3):279–86. PubMed

Egli D, Chen AE, Saphier G, Ichida J, Fitzgerald C, Go KJ, Acevedo N, Patel J, Baetscher M, Kearns WG, Goland R, Leibel RL, Melton DA, Eggan K. Reprogramming within hours following nuclear transfer into mouse but not human zygotes. Nature communications 2011 Jan;2:488. PubMed

Han SSW, Williams LA, Eggan KC. Constructing and deconstructing stem cell models of neurological disease. Neuron 2011 May;70(4):626–44. PubMed

Egli D, Eggan K. Recipient cell nuclear factors are required for reprogramming by nuclear transfer. Development (Cambridge, England) 2010 Jun;137(12):1953–63. PubMed

Ichida JK, Kiskinis E, Eggan K. Shushing down the epigenetic landscape towards stem cell differentiation. Development (Cambridge, England) 2010 Aug;137(15):2455–60. PubMed

Niakan KK, Ji H, Maehr R, Vokes SA, Rodolfa KT, Sherwood RI, Yamaki M, Dimos JT, Chen AE, Melton DA, McMahon AP, Eggan K. Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal. Genes & development 2010 Feb;24(3):312–26. PubMed

Kiskinis E, Eggan K. Progress toward the clinical application of patient-specific pluripotent stem cells. The Journal of clinical investigation 2010 Jan;120(1):51–9. PubMed

Chen AE, Egli D, Niakan K, Deng J, Akutsu H, Yamaki M, Cowan C, Fitz-Gerald C, Zhang K, Melton DA, Eggan K. Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines. Cell stem cell 2009 Feb;4(2):103–6. PubMed

Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, Huangfu D, Akutsu H, Liu DR, Rubin LL, Eggan K. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell stem cell 2009 Nov;5(5):491–503. PubMed

Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, Huangfu D, Akutsu H, Liu DR, Rubin LL, Eggan K. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell stem cell 2009 Nov;5(5):491–503. PubMed

Egli D, Sandler VM, Shinohara ML, Cantor H, Eggan K. Reprogramming after chromosome transfer into mouse blastomeres. Current biology : CB 2009 Aug;19(16):1403–9. PubMed

Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell stem cell 2008 Dec;3(6):637–48. PubMed

Egli D, Birkhoff G, Eggan K. Mediators of reprogramming: transcription factors and transitions through mitosis. Nature reviews. Molecular cell biology 2008 Jul;9(7):505–16. PubMed

Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science (New York, N.Y.) 2008 Aug;321(5893):1218–21. PubMed

Eggan K. Short-circuiting epiblast development. Cell stem cell 2007 Aug;1(2):131–2. PubMed

Egli D, Rosains J, Birkhoff G, Eggan K. Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature 2007 Jun;447(7145):679–85. PubMed

Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nature neuroscience 2007 May;10(5):608–14. PubMed

updated: 04/15/2014