Zeng Lab
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Xianmin Zeng, Ph.D., Associate Professor

Neuronal differentiation in human embryonic stem cells

Xianmin Zeng, Ph.D., is a member of the Buck Institute’s Stem Cell and Regenerative Medicine Program. Zeng’s work focuses on neuronal differentiation of human embryonic stem cells (hESCs), especially on generating authentic dopamine-producing neurons, the type of neurons that are degenerated and lost in Parkinson’s disease (PD) patients. These cells may not only provide a potential unlimited cell source for cell replacement therapy for PD, but also offer an unprecedented opportunity to develop screening models for assessing small molecule drugs and to clarify the mechanisms of disease.

The Zeng lab is particularly interested in molecular and cellular mechanisms that regulate the process of generating dopaminergic neurons from hESCs as well as in developing methods for isolating dopaminergic precursors from hESCs for transplantation therapy of PD and for drug screening.

Zeng, among others, established methods to efficiently generate neural stem cells and dopaminergic neurons with midbrain characteristics from hESCs, and reported the first transplantation of hESC-derived dopaminergic neurons in a rat PD model, as well as establishing the first in vitro hESC-based PD model. Her lab is currently developing genetically modified hESC lines and molecular tools that permit reliable observations as hESCs differentiate into dopaminergic neurons, and are developing cell sorting protocols for enriching dopaminergic precursors using cell surface markers.

Dr. Zeng is working closely with David Greenberg, M.D., Ph.D., and Mahendra Rao, M.D., Ph.D., on the development of the Institute’s stem cell program. She is Program Director of the Institute’s newly established CIRM (California Institute for Regenerative Medicine) Shared Research Laboratory and Stem Cell Techniques Course, which helps train the next generation of stem cell scientists. Dr. Zeng is also involved in several interdisciplinary projects with other groups at the Buck Institute. Her laboratory is collaborating with the Andersen laboratory in testing the efficacy of transplantation of hESC-derived dopaminergic neurons in reversing losses in motor function associated with animal models of PD. She is working closely with Dr. Bredesen’s lab to determine pathways of programmed cell death that are active in hESCs. She is also working with Judy Campisi, Ph.D., and Gordon Lithgow, Ph.D., to use hESCs to determine how cell cycle checkpoints and cellular tumor suppressor functions (apoptosis and senescence) develop during early and later changes in hESCs, as well as to use hESCs to explore the relationship between cell changes and cancer and aging.

“Without CIRM funding, we wouldn’t have gotten into this, given the barriers involved.”

- Dr. Xianmin Zeng,

 

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