Stem Cell Biology and Regenerative Medicine
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research
Research OverviewOur research is focused on understanding how genetic and environmental factors contribute to human neurodegenerative disease. The mammalian central nervous system is assembled from a diverse collection of neurons, each with its own unique properties. These discrete characteristics underlie the proper integration and function of each neuron within the circuitry of the brain and spinal cord. However, their individual qualities also render particular neurons either resistant or sensitive to particular degenerative stimuli. Thus, for each neurodegenerative disease, a stereotyped set of neuronal subtypes is destroyed, causing the hallmark presentation of that condition.
While animal models have been invaluable tools for identifying pathological mechanisms, this approach is usually limited to monogenic disease. Many common forms of disease that involve complex genetic and environmental factors cannot be addressed in this manner and remain difficult to study. Although primary human tissue could serve as an alternative, the central nervous system is usually not accessible until long after the causative events have occurred.
In order to overcome these challenges, we use cellular reprogramming and stem cell technology to build patient-specific in vitro models of neurodegenerative disease. Using precise combinations of transcription factors, small molecules, and growth factors, we can convert fibroblasts from patients into disease-affected neural cells while preserving their genotype. This enables mechanistic investigation of both familial and sporadic forms of neurodegenerative diseases and allows experimental control over genetic and environmental factors. We use a combination of chemical genetic, biochemical, and genetic tools to identify new pathological mechanisms and potential therapeutics using these models.
We are also using chemical, genetic, and bioinformatic tools to better understand defined-factor reprogramming. We are interested in identifying the epigenetic and biochemical pathways that regulate cell fate conversion. Our goals are to enable the construction of disease models that best mimic in vivo systems and to regenerate tissues and organs compromised by disease or injury.
Mailing Address 9080 HSC
Office Location BCC 307
Office Phone (323) 442-0063
Office Location BCC 307
- B.S. 2000 Microbiology and Molecular Genetics-UCLA
- Ph.D. 2006 Genetics-Harvard
Selected PublicationsView a complete PubMed search
- Ichida, J.K.*, Chung, J.C.*, Carter, A.C., Williams, L.A., Moura, M.T., Singh, S., Bock, C., Ziller, M., Amabile, G., Umezawa, A., Rubin, L.L., Bradner, J.E., Akutsu, H., Meissner, A., Eggan, K. Notch inhibition renders both oncogenic transgenes and p53 inhibition dispensable during iPSC reprogramming. Submitted.
- Egli, D., Chen, A.E., Saphier, G., Ichida, J., Fitzgerald, C., Go, K.J., Acevedo, N., Patel, J., Baetscher, M., Kearns, W.G., Goland, R., Leibel, R.L., Melton, D.A., Eggan, K. Reprogramming within hours following nuclear transfer into mouse but not human zygotes. Nature Communications. 2011 Oct 4; 2:488. doi: 10.1038/ncomms1503.
- 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 2;9(3):205-18. PubMed PMID: 21852222; PubMed Central PMCID: PMC3188987.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 6;5(5):491-503. Epub 2009 Oct 8. PubMed PMID: 19818703; PubMed Central PMCID: PMC3335195.PubMed
- Ichida JK, Horhota A, Zou K, McLaughlin LW, Szostak JW. High fidelity TNA synthesis by Therminator polymerase. Nucleic Acids Res. 2005 Sep 12;33(16):5219-25. Print 2005. PubMed PMID: 16157867; PubMed Central PMCID: PMC1214552PubMed
- Ichida JK, Zou K, Horhota A, Yu B, McLaughlin LW, Szostak JW. An in vitroselection system for TNA. J Am Chem Soc. 2005 Mar 9;127(9):2802-3. PubMed PMID:15740086.PubMed
- Chaput JC, Ichida JK, Szostak JW. DNA polymerase-mediated DNA synthesis on a TNA template. J Am Chem Soc. 2003 Jan 29;125(4):856-7. PubMed PMID: 12537469.PubMed