Our laboratory is interested in adult tissue regeneration and developing regenerative strategies to repair adult organs damaged in disease and injury.
With the exception of a few organ systems such as the liver, blood, and surface epithelium, adult mammals, including humans, possess very limited regenerative capacity. The regenerative response is mainly mediated by progenitors and stem cells that reside in some, but not all, adult organs. Currently, there are no effective means to regenerate most cell types in the body or to recreate complex structures that are composed of multiple cell types. To overcome these limitations, our laboratory focuses on developing novel regenerative strategies based on cellular reprogramming whereby exiting adult cells are converted into other cell types, including progenitors and tissue stem cells, in order to repair or rebuild adult organs in situ.
We currently employ two major model systems. The first revolves around endocrine islets of the pancreas, which harbor insulin secreting beta cells, the key cell type in the disease Diabetes. The second model focuses on the central nervous system, where specific neural populations or entire brain structures degenerate due to disease and injury.
To formulate reprogramming strategies, we are particularly interested in understanding the molecular machinery that maintains the stable state of adult cells. Such knowledge will allow us to instructively manipulate and reprogram adult cell fate. We are also using specific reprogramming models that we have developed to understand the molecular mechanisms that control cell reprogramming. We employ a wide variety of molecular, cellular, biochemical, and genetic techniques in our studies. Ultimately, we would like to work with clinicians to translate our basic research efforts into clinically relevant therapeutic strategies.
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References:
- Zhou Q and Melton DA. (2008) Extreme makeover: converting one cell into another. Cell Stem Cell 3(4): 382-388.
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Zhou Q, Brown J, Kanarek A, Rajagopal J, and Melton DA. (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455(7213): 627-632.
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Zhou Q, Law AC, Rajagopal J, Anderson WJ, Gray PA, and Melton DA. (2007) A multipotent progenitor domain guides pancreatic organogenesis. Dev. Cell 13: 103-114.
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Zhou Q and Anderson DJ. (2002) The bHLH transcription factors Olig2 and Olig1 couple neuronal and glial subtype specification. Cell 109: 61-73.
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