JAMES A. THOMSON, VMD, PHD

Research

In the early 1990s, my lab derived ES cells from an Old World monkey (the rhesus macaque) and a New World monkey (the common marmoset), work that led to derivation of human ES cells in 1998. Much of my lab’s research after that derivation was dedicated to establishing human ES cells as an accepted, practical model system. To that end, we developed defined culture conditions, methods for genetic manipulation, and approaches for the in vitro differentiation of human ES cells to key lineages of clinical importance including hematopoietic, neural, cardiac, and placental tissues. More recently, in 2007, my laboratory described the isolation of human induced pluripotent (iPS cells) cells with the basic properties of human ES cells but derived from somatic cells.

My research now focuses on understanding how a cell can maintain or change identity, how a cell chooses between self-renewal and the initial decision to differentiate, and how a differentiated cell with limited developmental potential can be reprogrammed to a pluripotent cell.

My current research interests include:

• Examining the transcriptional networks in ES cells that mediate self-renewal and commitment to each of the basic lineages of the early embryo.
• Mapping the epigenome of ES cells and their early-differentiated derivatives.
• Improving methods for generating human iPS cells, and correcting genetic defects in iPS cells generated from patients with degenerative retinal disease.
• Developing new strategies to convert human pluripotent stem and somatic cells into hematopoietic, vascular, and cardiac progenitor cells.
• Understanding clocking mechanisms that control developmental rates.

Publications

•  Hou Z, Zhang Y, Propson NE, Howden SE, Chu L, Sontheimer EJ, Thomson, JA. “Efficient Genome Engineering in Human Pluripotent Stem Cells Using Cas9 from Neisseria meningitides.” Proc Natl Acad Sci, USA, 110 (39): 15644-9 (2013). PMCID: PMC3785731.
• Cho M, Oh SS, Nie J, Stewart R, Eisenstein MS, Chambers J, Marth J, Walker F, Thomson, JA., Soh H. “Quantitative Selection and Parallel Characterization of Aptamers.” Proc Natl Acad Sci, USA, 110 (46): 18460-5 (2013). PMCID: PMC3831996.
• Phillips MJ, Perez ET, Martin JM, Reshel ST, Wallace KA, Capowski EE, Singh R, Wright LS, Clark EM, Barney PM, Stewart R, Dickerson SJ, Miller MJ, Percin EF, Thomson, JA., Gamm DM. “Modeling human retinal development with patient-specific iPS cells reveals multiple roles for VSX2.” Stem Cells. 2014 Feb 15. PMID: 24532057.
• Hou Z, Zhang J, Schwartz MP, Stewart R, Page CD, Murphy WL, Thomson JA. “A human pluripotent stem cell platform for assessing developmental neural toxicity screening.” Stem Cell Research & Therapy, 4(Suppl 1) (2013). NIHMS ID: 550666. PMCID: PMC3983661.
• Sengupta S, Johnson BP, Swanson SA, Stewart R, Bradfield CA, Thomson JA. “Aggregate Culture of Human Embryonic Stem Cell-Derived Hepatocytes in Suspension are an Improved In Vitro Model for Drug Metabolism and Toxicity Testing.” Toxicol Sci. 2014 Jul;140(1):236-45. PMCID: PMC4133588.

Mentor to METC Graduate Students:

• Morten Seirup (2012-2020)