Stem Cell Biology (Human & Mouse Embryonic Stem Cells)
Cell Reprogramming (Pluripotent Reprogramming & Direct Lineage Reprogramming)
Neurobiology (Neurodegenerative Diseases)
Embryonic stem (ES) cells
are unique in that they have the potential to generate any cell type in the body and, thus, are of great interest for regenerative medicine. Recently, there has been growing excitement about the potential use of ES cells in the treatment of a myriad of diseases ranging from diabetes to heart failure. However, to date, none of these cell types have been accepted as efficient replacements for patient specific cell types due to the ethical and technical problems associated with ES cell isolation, culture, and differentiation into therapeutic cell types.
The generation of living animals by nuclear reprogramming demonstrated that the epigenetic state of differentiation of somatic cells is labile and can be reset to an embryonic state that is capable of directing development of a new organism. A major breakthrough in solving these issues has been the in vitro derivation of somatic cells reprogrammed to the pluripotent state, designated as “induced pluripotent stem” or “iPS” cells by Yamanaka.
However, the technical difficulties associated with directed differentiation and concerns surrounding the potential tumorigenecity of iPS cells present significant barriers. Several recent studies have demonstrated the feasibility of direct lineage reprogramming from one somatic cell type into another, thereby bypassing the need for a pluripotent intermediate state. Most recently, we succeeded in developing the technology to convert mouse fibroblasts into induced dopamine (iDA) neurons which resemble midbrain dopamine neurons. These results have several implications for the potential use of reprogrammed cells for disease modeling and cell replacement therapy of degenerative diseases.
The ultimate goal of our research is to exploit new advances in stem cell biology and cellular reprogramming technology to develop a deeper understanding for the basis of neurodegenerative diseases, and ultimately to develop new therapies for these diseases.Our research focus on understanding the underlying mechanisms that mediate epigenetic reprogramming. To address this question we utilize the transgenic mouse system, with various molecular, cellular, and biochemical approaches. In parallel, we develop a human iPS cell-based discovery platform for degenerative diseases. Patient specific iPS derived specific cells can be used for in vitro drug screening and target validation as new clinically relevant disease models with the ultimate goal of developing personalized therapeutic interventions in complex multifactorial human diseases.