Stem Cells and Tissue Regeneration

Cellular and molecular basis of cutaneous wound healing and diseases with a "wound signature"

The powerful lure of the field of regenerative medicine is based on the promise of being able to engineer cells and tissues of the human body to restore parts lost to trauma or disease. Interestingly, regeneration imitates and adapts many processes found in embryogenesis and tissue morphogenesis. Therefore a thorough understanding of these developmental processes beginning with individual stem cells through the formation of functional three dimensional organs is a prerequisite to making this field a reality. Among the organs in the body, the mammalian skin has remarkable regenerative abilities and is thus a prime model for elucidating the fundamental mechanisms regulating stem cell fate, tissue regeneration and repair. In particular, the outer layer of the skin (the epidermis) is one of the few tissues that constantly regenerate throughout the lifetime of the animal. This capability renders it an ideal system to interrogate how stem cells fuel regeneration. Moreover, due to its protective function as a barrier from the external environment, the epidermis is constantly damaged and must mount a wound-healing program to rapidly restore tissue structure and function. Both through our work and that of others, important strides have been made in the discovery of the rules of tissue formation, the interactions that occur between different cells within an organ, and the mechanisms underlying the regulation of tissue homeostasis.

With the goal of advancing the field of cell-based therapies, tissue regeneration and repair, we are currently exploring three major foci in the lab:

Dissecting how stem cell decisions are made to generate and maintain a tissue.
Understanding how these decisions are skewed either during diseases (e.g. cancer, diabetes, and inflammatory diseases) or during physiological processes (wound-healing).
Elucidating the network of signals exchanged between epidermal cells and surrounding cells (cell-cell communications) within the organ to produce an appropriate wound-healing response.

Our laboratory employs a wide array of experimental techniques ranging from genetic engineering of mouse models to cell biology and biochemistry to quantitative biology. These multidisciplinary approaches are combined to gain a fundamental understanding of tissue homeostasis, and the human diseases such as cancer that arise when these regulatory mechanisms are perturbed. For example, the German pathologist Rudolph Virchow postulated a link between the wound-healing program and tumor development as early as the 1860's. Later Harold Dvorak compared tumors to chronic wounds and highlighted the parallels between the inflammatory, proliferative and remodeling phases of wound healing program and the characteristics of metastatic tumors. Consequently, though our research projects are firmly rooted in basic biology, they also have considerable potential to translate into the development of novel therapeutics for a variety of common diseases. These investigations occur under the auspices of a joint research laboratory sponsored by IFOM and the Institute for Stem Cell Biology and Regenerative Medicine (inSTEM). This collaborative venture offers access to state-of-the-art facilities and scientific talent of both IFOM and inSTEM/NCBS to make important and rapid advances in our research endeavors. Moreover, we maintain a long-standing collaboration with Professor Shyni Varghese in the Department of Bioengineering at the University of California, San Diego. Together we are analyzing how the cellular microenvironment impacts stem cell behavior and how perturbations in the extracellular matrix orchestrate disease progression. Collectively, these affiliations provide the basis for the development of an integrated, world class, academic research laboratory with a unique ability to advance both basic and translational aspects of stem cell research and tissue regeneration.