Dr. Bryan is a world-renowned expert on nitric oxide and nitrosylation, who has developed methods to detect nitric oxide as well as discovering an endocrine function of nitric oxide via the formation of S-nitrosoglutathione and inorganic nitrite. Dr. Bryan was hired to the faculty of the University of Texas Health Science Center at Houston by Dr. Ferid Murad (please see below), and is now Adjunct Professor, Dept. of Molecular and Human Genetics, Baylor College of Medicine.
“I have worked in the nitric oxide/nitrosylation field for more than 15 years and believe that SAJE’s GSNOR inhibiting technology is novel, innovative, and likely to produce many drugs to treat a wide variety of important inflammatory, oxidant-based, and fibrotic diseases. Furthermore, having worked with SAJE’s drugs in my own lab, I am impressed by their therapeutic activities and predict that they will be successful in the clinic. The only remaining clinical issue I see is potential toxicity, but I have seen no evidence of it at extremely high doses in my studies and SAJE’s recent safety results are quite encouraging in their lack of toxicity”
- Nathan Bryan, Ph.D.
Dr. Hurley is the world’s leading expert on S-nitrosoglutathione reductase (GSNOR), having first cloned the full length human GSNOR gene and expressed it in bacteria. He determined the crystallographic structure of GSNOR with SAJE inhibitors bound into the active site and has helped SAJE with the SAR of GSNOR and in vitro testing of its novel GSNOR inhibitors. Dr. Hurley is the Acting Chair, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine.
“I developed the expression system for human GSNOR and solved its three-dimensional structure by X-ray crystallography. More recently, I solved the X-ray structure of GSNOR bound to several of SAJE’s original drugs which block the active site of the enzyme and helped the Company with its SAR work. I am impressed by the progress SAJE has made on both the chemistry and biology fronts and strongly believe this progress has substantially reduced the risks associated with their development program.”
- Thomas Hurley, Ph.D.
Dr. Lefer has been working in the fields of myocardial protection and coronary physiology for over 20 years and has made important contributions to these fields. Dr. Lefer’s laboratory was among the first to demonstrate the profound loss of endothelial cell derived nitric oxide (NO) from the coronary circulation following coronary artery occlusion and reperfusion. A series of subsequent studies in both small and large animal models clearly demonstrated that oxidative stress occurring within the first few minutes of reperfusion significantly impaired NO generation by coronary endothelial nitric oxide synthase (eNOS). Dr. Lefer’s laboratory was the first to report on the potent cardioprotective actions of NO in the setting of acute myocardial infarction and congestive heart failure in both small and large animal models. Dr. Lefer has investigated nitrite-based therapies in a number of models of chronic tissue ischemia and ischemia-reperfusion injury. Dr Lefer is Director, Cardiovascular Center of Excellence, Professor of Pharmacology, Louisiana State University School of Medicine.
"My work in NO and now GSNOR inhibition has lead me to recognize the importance for pharmacology of SAJE’s GSNOR inhibitors. They are highly active in models of diabetes, NASH, heart attack, and heart failure and should lead to life changing medicines."
- David J. Lefer, Ph.D.
Dr. Murad won the Lasker Prize in 1996 and the Nobel Prize in 1998 for discovering that nitric oxide is the endothelial relaxing factor. That discovery forms one of the foundations of SAJE’s technology. SAJE’s compounds do not produce nitric oxide directly, although they are related to nitric oxide in that they increase the level of nitrosylation on critical proteins in therapeutic signal transduction pathways. Given his Nobel Prize in the nitrosylation field and his current expertise in it, Dr. Murad supports and advises our drug discovery and development efforts. He is Professor of Medicine at the Stanford University School of Medicine, and Senior Research Advisor at the Palo Alto Veterans Research Institute, and President of the Murad Foundation.
“I think that what SAJE is doing is some of the most exciting work in the nitric oxide/nitrosylation field. I can see many novel and important therapies coming from their work. It is well established as fundamental science that inhibiting GSNOR regulates the intracellular nitric oxide/nitrosylation pathways as pleiotropic signal transduction systems that have been in evolution for a billion or more years. The physiological role of this system is the maintenance and or restoration of homeostasis during various disease processes. Utilization of this GSNOR regulated signal transduction system to correct aberrant cellular responses and restore tissue homeostasis is a novel therapeutic approach that takes advantage of normal self-limiting cellular mechanisms. The inhibition of GSNOR minimizes the immunological and cellular overreactions that result in fibrosis with few, if any, off-target effects. SAJE has shown that inhibiting GSNOR has major therapeutic activities that should translate into important human drugs.”
- Ferid Murad, M.D., Ph.D.
Dr. Pasquale is Professor of Ophthalmology, Site Chair, Department of Ophthalmology, Mount Sinai Hospital, Deputy Chair, Ophthalmology Research, Icahn School of Medicine at Mount Sinai, Director, Mount Sinai / NYEE Eye and Vision Research Institute. Dr. Pasquale is a member of the PLOS One, Journal of Glaucoma, International Glaucoma Review and American Journal of Ophthalmology editorial boards. He currently serves as chair of the American Glaucoma Society Research Committee and is a member of the National Institute of Health’s National Advisory Eye Council. He is a Gold Fellow of ARVO and a member of the American Ophthalmological Society and the Glaucoma Research Society. He has given numerous named lectures and keynote presentations throughout the world. Dr. Pasquale is an NIH Principal Investigator with continuous support since 2006. His research, which leverages the rich resources available in the Nurses Health Study, Health Professional Follow-up Study and the Women’s Genome Health Study, focuses on the discovery of primary prevention strategies in the open-angle glaucomas. His work has highlighted environmental risk factors for exfoliation syndrome.
“SAJE’s technology will untie the Gordian Knot of neurodegeneration in the retina and brain and should lead to advances in the pharmaceutical treatment of many ophthalmic diseases ”
She is Associate Professor of Neurobiology and Anatomy, Wake Forest School of Medicine. The Sappington laboratory focuses on understanding the molecular and cellular events at the intersection of neuron failure, neuroinflammation and pathological progression of neurodegenerative disease. To identify molecular pathways and cellular events involved in disease and to develop pharmacological and regenerative therapies, we use a variety of approaches, including: in vitro and in vivo experimental models, basic molecular and cellular biology, cell and tissue histology, electrophysiology, live cell imaging, in vivo imaging, neural tracing and neurobehavioral assays. Degeneration of retinal ganglion cells (RGCs), whose axons form the optic nerve share many cellular characteristics with neurodegenerative diseases elsewhere in the central nervous system (CNS), including Alzheimer’s disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease. These characteristics include: 1) functional failure that precedes cell loss, 2) axonal degeneration that precedes cell soma loss and 3) induction of neuroinflammatory responses by glial cells. Drs. Pasquale and Sappington have collaborated together for many years in research in ocular diseases.
“SAJE’s drugs are very exciting in the ocular space. I can see many applications for unmet needs in ocular therapy”
- Rebecca Sappington, Ph.D.
Since its inception, SAJE has also utilized the knowledge and talents of a large number of academic and industrial advisors and collaborators. Our academic collaborators include those from Duke University, The University of Maryland, Indiana University, The University of Texas, The University of Montana, Montana State University, The Buck Institute for Research on Aging, the NIH, Johns Hopkins University, Louisiana State University School of Medicine, Vanderbilt University School of Medicine, Wake Forest University Medical School, Stanford University, and Harvard University.
SAJE also utilizes industrial advisors from the Battelle Memorial Institute, Covance, and the biopharmaceutical consulting firm of Synergy Partners, with Drs. James MacDonald and Catherine Strader, the principals of that firm, who are former colleagues of Dr. Bradley’s at Merck.