Research

Dr. Gregory SchultzDr. Gregory Schultz, PhD, Professor of OB/GYN

Dr. Schultz’s research focuses on the molecular regulation of wound healing, and the imbalances that lead to chronic wounds or hypertrophic scars. His antiscarring research focuses on using antisense oligonucleotides and AAV-vectored ribozymes and siRNAs targeting mRNAs for transforming growth factor beta (TGFb) and connective tissue growth factor (CTGF), which are the two most important growth factor systems that regulate scarring. Target tissues include skin, cornea and peritoneal adhesions. Dr. Schultz’ research on chronic wounds has shown that the major cause for non-healing is the presence of bacterial biofilms that stimulate chronic inflammation and lead to chronically elevated proteases that degrade proteins that are essential for healing. He currently is conducting clinical trials on a rapid point-of-care detector for proteases in wound fluids combined with topical treatments that inhibit proteases (doxycycline) and patented bacterial barrier dressings with a unique non-leaching microbicidal polymer.

Dr. Gregory Schultz’s current research program focuses on several basic and applied projects. One long term research area that has been continuously funded for 24 years by the National Eye Institute (NEI) of the National Institutes of Health (NIH) centers on defining the molecular regulation of scarring in the cornea. Dr. Schultz’s research has shown that the transforming growth factor beta (TGFβ) system and the connective tissue growth factor (CTGF) systems interact to regulate scarring in the eye, as well as in other tissues, including skin and peritoneal cavity. Prolonged, elevated activities of the TGFβ and CTGF systems in corneal wounds lead to excessive accumulation of scar tissue and transformation of fibroblasts into myofibroblasts, which clinically produces corneal haze in the eye. Similarly, prolonged, elevated activities of the TGFβ and CTGF systems produces hypertrophic scarring in the skin, and leads to adhesions in the peritoneal cavity. Current research activities on this project are to better define the different patterns of gene expression regulated by the N-terminal and C-terminal domains of CTGF and to further develop gene-targeted therapies that selectively reduce expression of TGFβ and CTGF mRNAs and proteins using ribozymes, antisense oligonucleotides (ASOs) and siRNAs that are delivered by adenoassociated virus (AAV) vectors. In collaboration with Excaliard Pharmaceuticals, Inc., clinical trials will begin in 2009 to assess the anti-scarring effects of ASOs targeting CTGF in skin wounds.

Another current research area is the development of rapid, point-of-care (POC) detectors for sentimental proteins that indicate the molecular status of chronic wounds. Previous data from Dr. Schultz’s lab linked elevated level of matrix metalloproteinases (MMPs) in chronic wound fluids and biopsies with poor wound healing. In collaboration with Emergent Technologies, Inc., and Auxano Diagnostics, Inc., Dr. Schultz’s lab developed the first, rapid, POC detector that measures MMP activities in chronic wound fluid samples. Final clinical assessment and validation of the MMP detector is underway and clearance in Europe (CE marking) is anticipated in 2009 with FDA clearance target for 2010.

A third area of current research is to develop rapid screening devices and therapies for treatment of acute sulfur mustard injuries to the eye, skin and lungs. Sulfur mustard is a high threat chemical weapon agent, and this project is part of an $18 million NIH U54 CounterACT grant that is centered at Lovelace Respiratory Research Institute in Albuquerque, NM. Dr. Schultz and collaborators in the Departments of Chemistry and Materials Engineering at the University of Florida are identifying sentinel proteins that are alkylated by sulfur mustard and can be used to assess the extent of exposure of persons to sulfur mustard. The collaborative group is also assessing the effects of topical and systemic drug treatments to reduce the acute blistering effects of sulfur mustard.

Other active collaborative projects include an ongoing NIH clinical trial assessing topical doxycycline treatment of chronic diabetic foot ulcers and the development of ribozymes to treat acute and recurrent infections of the eye by herpes simplex virus (HSV).