Adult stem cells are the engines of tissue regeneration. Usually held dormant, stem cells are sparked into action in response to injury and generate both the mature cells needed to repair tissue while also replenishing its stem cell reserve. This process is stimulated by a series of temporally and spatially staged microenvironmental factors. In aging, stem cell-driven tissue regeneration declines progressively due to altered composition of the extrinsic niche microenvironment as well as intrinsic changes to the signaling and transcriptional networks that underlie cell fate determination.

Our multi-disciplinary group of biomedical engineers, stem cell biologists, and systems biologists is broadly interested in understanding how stem cells use the integrative action of their regulatory circuitry to interpret and balance diverse streams of microenvironmental “information”.  We utilize mouse model systems that exhibit aging-related declines in regenerative capacity, including skeletal muscle, liver, and hematopoietic tissues. In particular, we focus on these main areas of investigation:

(1) We engineer biomimetic microenvironments for evaluating stem cell–niche interactions.

(2) We develop single-cell assay and modeling approaches to deconstruct how stem cell fate outcomes are dictated by diverse niche microenvironmental cues. In particular, we focus on elucidating how heterogeneous stem cell fate outcomes emerge from deterministic signaling and regulatory circuits.

(3) We deconvolve the logic-based communication networks of overlapping autocrine and paracrine signals used by stem cells to communicate with their surrounding microenvironment.

(4) We develop molecular imaging strategies to dynamically and quantitatively evaluate tissue regenerative processes in living animals.

These approaches will enable the improvement of rationally designed, quantitatively predictable stem cell-targeted regenerative medicine therapies to treat tissue aging and degeneration.

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