The Zeng lab focuses on developing a model system to investigate developmental processes of the central nervous system and molecular mechanisms of age-related neurodegenerative disorders using human pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs are reprogrammed stem cells that are akin to ESCs but offer the advantage of being able to be generated from any individual at any point. Over the past decade, we have demonstrated success in utilizing this system to study disease mechanisms of neurodegenerative disorders (with a focus on Parkinson’s disease and Alzheimer’s disease), to identify key developmental regulators of the process of neural development, and to develop cell- and small molecule–based therapeutic targets for neurodegenerative disorders.
Why it matters
The reprogramming of a variety of cell types into iPSCs is a landmark event in biomedical history. It is now possible to reprogram somatic cells obtained from an individual patient into iPSC and subsequently differentiate them into neurons, cardiac cells, liver cells, and so on. This creates two major opportunities. The first is that in degenerative disease, where cells are dying, there is the opportunity to reintroduce those cells to restore function. The second is that cells in a dish can be tested against a panel of possible drugs to find the optimized treatment for that individual patient. These cell cultures derived from patients may be a more accurate model of the disease than animal models. We believe that the development and implementation of iPSC-based disease models will create a more efficient disease-specific process underpinned by the biological mechanism in a patient- and disease-specific manner rather than by trial and error.
The goal of my laboratory is to use stem cells for the development of replacement therapy for neurodegenerative disorders and drug discovery as well as disease modeling.
Xianmin Zeng, PhD
Dr. Zeng is a leading stem cell biologist and professor at the Buck Institute. Her laboratory studies neurodegenerative diseases using iPSCs as a model system. She has also developed clinical-grade iPSC lines and scalable processes of generating functional neural cells for cell therapies and drug screening.
Dr. Zeng received her PhD from Technical University of Denmark in 2000 and completed her postdoctoral training at the National Institutes of Health. She joined the Buck Institute in 2005, where she helped build the the Institute’s Stem Cell Program. Dr. Zeng is a recipient of several major funding sources, including a translational grant from CIRM.
- Momcilovic, O., Sivapatham, R., Oron, T. R., Meyer, M., Mooney, S., Rao, M. S., Zeng, X. (2016 May 18). Derivation, characterization, and neural differentiation of integration-free induced pluripotent stem cell lines from Parkinson’s disease patients carrying SNCA, LRRK2, PARK2, and GBA mutations. PLoS One,11(5), e0154890. DOI: 10.1371/journal.pone.0154890. eCollection 2016. PMID:27191603.
- Shaltouki, A., Sivapatham, R., Pei, Y., Gerencser, A. A., Momcilovic, O., Rao, M. S., Zeng, X. (2015 Apr 2). Mitochondrial alterations by PARKIN in dopaminergic neurons using PARK2 patient-specific and PARK2 knock-out isogenic iPSC lines. Stem Cell Reports, pii, S2213-6711(15)00075-2. DOI: 10.1016/j.stemcr.2015.02.019. [Epub ahead of print] PMID: 25843045.
- Pei, Y., Sierra, G., Sivapatham, R., Swistowski, A., Rao, R. M., Zeng, X. (2015 Mar 17). A platform for rapid generation of single and multiplexed reporters in human iPSC lines. Sci Rep, 5, 9205. DOI: 10.1038/srep09205. PMID: 25777362.
- Zdravkovic, T., Nazor, K. L., Larocque, N., Gormley, M., Donne, M., Hunkapillar, N., Giritharan, G., Bernstein, H. S., Wei, G., Hebrok, M., Zeng, X., Genbacev, O., Mattis, A., McMaster, M. T., Krtolica, A., Valbuena, D., Simón, C., Laurent, L. C., Loring, J. F., Fisher, S. J. (2015 Oct 19). Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification. Development, pii, dev.122846. [Epub ahead of print].
- Awad, O., Sarkar, C., Panicker, L. M., Miller, D., Zeng, X., Sgambato, J. A., Lipinski, M. M., Feldman, R. A. (2015 July 28). Altered TFEB-mediated lysosomal biogenesis in Gaucher disease iPSCs-derived neuronal cells. Hum Mol Genet, pii, ddv297. [Epub ahead of print] PMID:26220978.
- Pei, Y., Peng, J., Behl, M., Sipes, N. S., Shockley, K. R., Rao, M. S., Tice, R. R., Zeng, X. (2015 Aug 5). Comparative neurotoxicity screening in human iPSC–derived neural stem cells, neurons, and astrocytes. Brain Res, pii, S0006-8993(15)00593-4. DOI: 10.1016/j.brainres.2015.07.048. [Epub ahead of print] PMID: 26254731.
- Peng, J., Liu, Q., Rao, M. S., Zeng, X. (2014 Sep). Survival and engraftment of dopaminergic neurons manufactured by a GMP-compatible process. Cytotherapy, 16(9), 1305–12.