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Dr. Tang:

Dr. Tang 101
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Dr. Tang's CV in brief

Publications

Protein Studies Research Program

Jordan J.N. Tang, Ph.D. Member and Program Chair, Protein Studies Research Program J.G. Puterbaugh Chair in Medical Research Adjunct Professor, Department of Biochemistry and Molecular Biology, University   of Oklahoma Health Sciences Center

Research Interests
Alzheimer’s disease inflicts itself upon 18 million people worldwide and may affect up to 24 million by 2025. It is a major cause of death for adults, yet no effective drug exists to slow or stop the progression of the disease. In 1999, we identified a protease called memapsin 2, or beta-secretase, a brain protease which initiates a selective proteolysis of beta-amyloid precursor protein (APP) leading to the production of amyloid-beta (Ab). The accumulation of Ab in the brain is a major factor in the pathogenesis of Alzheimer’s, so memapsin 2 has emerged as a major target for the development of inhibitor drugs to treat the disease. In recent years, we have studied the structure-function relationships of memapsin 2, including the specificity, crystal structure and the development of potent first-generation inhibitors. These are basic tools that enable inhibitor development.

A major current effort lies in the design, synthesis and testing of new generations of memapsin 2 inhibitors with clinical potential. Results from basic studies have permitted us to use structure-based design cycles. In this approach, we use crystal structures of memapsin 2 complexed with inhibitors to gain insights and to produce better next generation inhibitors. Such studies have brought us small, potent and selective inhibitors capable of inhibiting memapsin 2 in biological systems.

We are also attempting to understand the regulation of memapsin 2 in physiological and pathological settings. Since memapsin 2 is an aspartic protease that optimally functions in an acidic environment, its internalization from cell surface to endosomes is important in cellular trafficking for the hydrolysis of APP. We discovered that the endocytosis of memapsin 2 is facilitated by its association with APP, while recycling of memapsin 2 is mediated by various factors, including GGA, retromer and the phosphorylation of memapsin cytosolic domain. It seems likely that these processes are involved in the regulation of Ab production and the pathogenesis of Alzheimer’s disease.

Together, these studies will hopefully lead to the design of memapsin 2 inhibitor drugs for Alzheimer’s disease, a better understanding of the physiological functions of memapsin 2 and the consequences of its inhibition.

Joined OMRF Scientific Staff in 1966.
(First joined OMRF in 1958.)

Mailing Address
Protein Studies Research Program, MS 28
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-6673
Fax: (405) 271-3980
E-mail: Jordan-Tang@omrf.org