Marion Gordon, PhD

Associate Professor

Pharmacology and Toxicology

Lab Affiliation: Gerecke-Gordon Lab

Education & Training

PhD - Biochemistry - Rutgers University, Piscataway, NJ
BA - Chemistry /French - Douglass College, New Brunswick, NJ
Post-Doctoral Fellowship - Anatomy and Cell Biology - Harvard Medical School, Boston, MA
Post-Doctoral Fellowship - Molecular, Cellular and Developmental Biology - Tufts University School of Medicine, Boston, MA

Research Interests

For the past 35 years I have been passionate about trying to understand the roles of extracellular matrices (particularly the collagens), in facilitating the functions of tissues and organs. A portion of my work has addressed the attachment of epithelial layers to their subjacent stromal layers. My research project within the UMDNJ/Rutgers CounterACT program project grant is to identify ocular treatments for civilian exposures to the potential terrorist agent, sulfur mustard (SM). SM was used in WWI, in the Iran-Iraq war of the 1980s, and in Syria in 2015 by ISIS. It is easy to synthesize and can easily be released in enclosed areas. There are no therapies known to promote healing of SM injuries. The alkylating agent has many sites of action: one that we address is the basement membrane zone (BMZ) under the epithelial cells of the eye and the skin. SM causes destruction of the anchoring complexes in the BMZ that hold the epithelial layer to its stromal layer. We and others have shown mustards induce matrix metalloproteinase-9. This MMP degrades the α6β4 integrin in the hemidesmosomes that “rivets” the epithelial layer to the stroma. Our lab is the first to show that mustards also induce ADAM17, which cleaves transmembranous collagen XVII, the other anchoring molecule in the hemidesmosome. It is the cleavage of these 2 proteins in cornea and skin that disrupts the integrity of the epithelial-stromal/dermal-epidermal junction and results in blisters. The blisters occur in the same cleavage plane as those seen in junctional epidermolysis bullosa, bullous pemphigoid, and UVB sunburns in skin, and we have used this fact to learn about the targets of SM. In the cornea, separations appear as microbullae (micro blisters), likely because of the relatively dehydrated state of the cornea as compared to the skin. When enough microbullae accrue, the epithelium sloughs. Healing after mustard injury is often defective, with long term adverse consequences. Since work with SM is not permitted at the university, we use nitrogen mustard (NM) to do preliminary experiments on organ cultured rabbit corneas. When potential therapies show promising results, they proceed to in vivo SM exposures of rabbit eyes. This work is contracted out to approved facilities such as Battelle or MRI Golbal. For the current proposed work, MRI Global will be the site for in vivo SM exposures. The approach of using NM-exposed corneal organ cultures, followed by in vivo SM ocular exposures, has been validated: Both mustards cause the same damage at the basement membrane zone as assessed by histology and electron microscopic ultrastructure. The adhesion complex is destroyed by both vesicants, with separations observed between the epithelial and stromal layers. Only the degree of injury is different, with NM being somewhat less damaging than SM (Gordon et al., J. Ocul. Pharmacol. Ther., 2010). Having been funded since 1988, first for my work on collagens and their roles in corneal structure and function, and now through the CounterACT program, I have acquired considerable experience in managing grants and directing lab personnel to successfully achieve the goals of the grants. Because mustards target the BMZ, as a molecular and cell biologist with an expertise in extracellular matrix, I bring a unique perspective to our CounterACT Center. The analyses performed to gauge the healing that occurs in mustard-wounded corneas, plus and minus treatment therapies, are assessed by at least 4 parameters found to be consistent in mustard exposed corneas (explained in the grant). The work will help identify drugs that should be stored in emergency response centers in case of a terrorist attack or a natural disaster involving SM exposure.

Publications

Awards

2017 - Elected to serve as Co-chair of the Collagen Gordon Conference
2012 - Named Fellow of the American Association of Anatomists