The research in my lab has been focused on the redox biology of cancer development and diseases associated with aging. We have pioneered in the effort to use novel methods to trap reactive oxygen intermediates in biological systems and to characterize their reaction products with biological macromolecules. We discovered in 1988 that nitrone-based free radical traps have neuroprotective activity in experimental models of brain ischemia/reperfusion, even if the nitrone (a-phenyl-tert-butyl nitrone i.e. PBN) is administered up to an hour after the stroke has occurred. This led to my co-founding of Centaur Pharmaceuticals in 1992, which devoted intense activity in commercializing nitrone-related therapeutics for the treatment of neurodegenerative diseases. Arising from this effort, a co-development partnership with AstraZeneca led to the development of a nitrone experimental drug, NXY-059, which went into clinical trials in acute ischemic stroke. This novel therapeutic was taken into worldwide phase 3 clinical trials.
My academic research effort for the last 15 years has focused on the basic science/translational science interface. We have helped pioneer in the role of gamma tocopherol in neurodegenerative diseases. In 2000, we and our collaborators discovered that PBN had anti-cancer activity. This led to our most recent research that has been devoted to understanding the anti-cancer activity of PBN and some of its congeners in an experimental hepatocellular carcinoma (HCC) model. Our reserach now has been extended into experimental models of colon cancer, breast cancer and glioblastoma. Recently we have investigated the anti-cancer activity of a novel proprietary nitrone OKN-007 in glioblastoma and breast cancer. The basic translational research in this area continues to be positive as a result of this we formed a start-up company, Onconos LLC, to begin commercializing OKN-007 for the treatment of glioblastomas. We expect to enter clinical trials within the next two years.
The basic research in my laboratory involves the role of reactive nitrogen species (RNS) and reactive oxygen species (ROS) in processes associated with the development of important diseases of aging with primary focus on events that occur in early phases of cancer development. We have focused most recently on the basic mechanism involved in the anti-cancer activity of nitrones. Specific nitrones have very potent biological action in curtailing the production of ROS and RNS, which are important in the development of many diseases of aging.
Our past effort has focused on the role of excess ROS and RNS production in the initiation and progression of cancers. We have discovered that certain nitrones will inhibit experimental liver cancer development. Specific research focus has been on the preventive action of a-phenyl-tert-butylnitrone (PBN) in liver cancer development in rats. The results have shown that PBN inhibits hepatocellular carcinoma formation. Current research is devoted to understanding at the molecular level the inhibiting action of PBN and related nitrone in animal models of cancer.
Most recently this effort has caused us to focus our efforts on enzymes especially Sulf2 in the extracellular matrix on the action of OKN-007 on the action of Sulf2 in altering the sulfation of heparin sulfate which controls growth factor signaling. This research has extended into the role of stem cells in cancer associated fibroblasts (CAF) and how nitrones alter growth factor signaling between CAFs and tumor cells.
We have extended our studies in to the action of nitrones plus other antioxidants on the inhibition of hearing loss caused by noise trauma. These studies have been done in collaboration with Dr. Richard Kopke at the Hough Ear Institute. We showed that a combination of a nitrone plus N-acetylcysteine (NAC) if administered soon after noise trauma, prevents permanent hearing loss. We have partnered with Dr. Kopke to take advantage of this discovery and we have recently formed a start-up company (Otologic Pharmaceutics, Inc.) to commercialize this technology to develop products to prevent noise induced hearing loss.
B.S., University of Kentucky, 1963
M.S., University of Kentucky, 1965
Ph.D., Purdue University, 1969
Post-doctoral studies, University of California at Davis, 1968-69, and University of Pennsylvania, 1969-71
Honors and Awards
1991 Glenn Foundation Award for Medical Research
1992 Member, Basic Biological Research Panel, National Task Force on the NIH Strategic Plan
1994 Fellow of the Oxygen Society
1995 Member, Executive Committee of the Oklahoma Center for Neurosciences
1996 Top Research Award and Gold Medal, American Aging Association
2005 Member, Strategic Planning Committee of 5-Year Plan for NIEHS
2007 Discovery Award, Society for Free Radical Biology and Medicine
Service on editorial boards of numerous scientific journals; faculty for courses at the University of Oklahoma School of Medicine; review panels and committees for the National Institutes of Health, American Cancer Society and others; co-founder and Board Member of Centaur Pharmaceuticals, Inc.; serves as Chairman of the Scientific Advisory Board; and serves as Vice President of Development, Onconos, LLC. and Chief Scientific Officer of Otologic Pharmaceuticals, Inc.
American Association for Cancer Research
American Society of Biological Chemists
Society for Neuroscience
Joined OMRF Scientific Staff in 1974
Du X, West MB, Cai Q, Cheng W, Ewert DL, Li W, Floyd RA, Kopke RD. Antioxidants reduce neurodegeneration and accumulation of pathologic Tau proteins in the auditory system after blast exposure. Free Radic Biol Med. 2017 Apr 22;108:627-643. [Epub ahead of print][Abstract] PMID: 2843865
Lu J, Li W, Du X, Ewert DL, West MB, Stewart C, Floyd RA, Kopke RD. Antioxidants reduce cellular and functional changes induced by intense noise in the inner ear and cochlear nucleus. J Assoc Res Otolaryngol 15:353-372, 2014. [Abstract]
Du X, Ewert DL, Cheng W, West MB, Lu J, Li W, Floyd RA, Kopke RD. Effects of antioxidant treatment on blast-induced brain injury. PLoS One 8:e80138, 2013. [Abstract]
Choi CH, Du X, Floyd RA, Kopke RD. Therapeutic effects of orally administrated antioxidant drugs on acute noise induced hearing loss. Free Radic Res 48:264-272, 2014. [Abstract]
Floyd RA, Castro Faria Neto HC, Zimmerman GA, Hensley K, Towner RA. Nitrone-based Therapeutics for Neurodegenerative Diseases. Their use alone or in Combination with Lanthionines. Free Radic Biol Med 2013. [Abstract] EPub
Towner RA, Gillespie DL, Schwager A, Saunders DG, Smith N, Njoku CE, Krysiak RS, III, Larabee C, Iqbal H, Floyd RA, Bourne DW, Abdullah O, Hsu EW, Jensen RL. Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007. Neuro Oncol 15:330-340, 2013. [Abstract]
Zheng X, Gai X, Han S, Moser CD, Hu C, Shire AM, Floyd RA, Roberts LR. The human sulfatase 2 inhibitor 2,4-disulfonylphenyl-tert-butylnitrone (OKN-007) has an antitumor effect in hepatocellular carcinoma mediated via suppression of TGFB1/SMAD2 and Hedgehog/GLI1 signaling. Genes Chromosomes Cancer 52:225-236, 2013. [Abstract]
Du X, Chen K, Choi CH, Li W, Cheng W, Stewart C, Hu N, Floyd RA, Kopke RD. Selective degeneration of synapses in the dorsal cochlear nucleus of chinchilla following acoustic trauma and effects of antioxidant treatment. Hear Res 283:1-13, 2012. [Abstract]
Ewert DL, Lu J, Li W, Du X, Floyd R, Kopke R. Antioxidant treatment reduces blast-induced cochlear damage and hearing loss. Hear Res 285:29-39, 2012. [Abstract]
Experimental Therapeutics Research Laboratory, MS 43
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7580
Fax: (405) 271-1795