Skin is biologically equipped to repair itself. It contains specific, epidermal stem cells that throughout our lifetime perpetually replenish the skin cells as they differentiate and shed off. When a wound occurs, the biological process of wound healing activates many cells at the site of injury resulting in migration, vascularization and cell division, thus closing the gap and repairing the injury. Translated to the cellular "language", cells at the site of injury release multiple molecules termed growth factors and cytokines, which in turn regulate specific gene expression. These genes produce the effector-molecules that guide and govern the process of wound healing.

The overall goal of our translational program in wound healing is to understand the molecular and cellular mechanisms of tissue repair and regeneration in skin and its pathogenesis, by integrating knowledge at the bench with clinical outcomes at the bedside. This includes identifying which molecular and cellular mechanisms are utilized during normal, acute wound healing process and identifying what molecular events lead to wound healing impairment in chronic (non-healing) wounds and further, developing local sustained gene delivery mechanisms for their treatment. Consequential to the extended life span of the modern human population and increased prevalence of diabetes, we are faced with epidemic proportions of chronic wounds such as diabetic foot ulcers, pressure (bed) sores and venous ulcers, which are the leading cause of lower-leg amputations in the elderly, as well as in the diabetic populations. Our recent discoveries include identification of the first genes (oncogene c-myc and b-catenin pathways) that inhibit healing in human chronic wounds and finding of molecular basis of debridement procedure.

Molecular Mechanisms of Cutaneous Wound Healing.
This project focuses on identification of the regulators of normal wound healing, such as corticosteroids and retinoids, understanding molecular mechanisms of their action and how they regulate the wound healing process. We have developed experimental model in which we use human skin organ cultures to study the effects of wound healing regulators and their specific role in this process.

Wound Genome Project
The primary goal of this research is to determine a specific group of genes responsible for inhibition of healing in patients with chronic wounds and identify molecular markers that can be utilized as prognostic and diagnostic indicators of clinical outcomes. We quantify changes in gene expression using large scale microarray technology and correlate our findings with clinical outcomes (rate of healing). The synergy of genomics with clinical outcomes, will provide a rational basis for prevention and future therapy of chronic wounds and reduce morbidity and mortality associated with chronic wounds.
Molecular Pathology of Chronic Wounds
Our goal is to identify molecular events that lead to development of chronic wounds utilizing patients? biopsies and genomics approach as well as molecular, biochemical and cellular biology techniques. We grow primary cells from patients? biopsies to functionally evaluate our findings. Our interests are defining the role of aging, neuropathy, obesity and diabetes in development of chronic ulcers.

From Bench to Bedside: Topical Gene Delivery Mechanisms
Genomics approach identifies multiple molecules as potential targets for therapeutic intervention in treatment of chronic wounds. The focus of this project is to utilize novel technologies of topical, sustained release of combination of growth factors that will accelerate the healing of chronic wounds in patients. In collaboration with the Wound Healing Program at Columbia University College of Physicians and Surgeons, we are currently developing methodology for topical gene delivery using adenovirus vectors and biodegradable polyanhydride polymers as a paradigm of the local sustained delivery of multiple growth factors at the wound site