Biography:

Alexei Basnakian received his PhD and DSc degrees from the Russian Academy of Medical Science, both in the field of DNA-degrading enzymes. He had postdoctoral trainings in molecular biology at the Harvard Medical School and in toxicology/cancer research at the National Center for Toxicological Research/U.S. Food and Drug Administration. Dr. Basnakian is a tenured Professor at the Department of Pharmacology and Toxicology, and Director of the DNA Damage and Toxicology Core Center at the University of Arkansas for Medical Sciences, and Research Career Scientist at the Veterans Hospital in Little Rock, Arkansas, USA. He is an author of 87 peer-reviewed papers and 14 reviews or book chapters. Dr. Basnakian is an Editorial Board member of four biomedical journals, and a member of NIH, AHA and VA grant study sections. His research interests are in DNases/endonucleases and DNA damage associated with toxicity, anti-cancer therapy, tissue injury and cell death.

Abstract:

Statement of the Problem: Deoxyribonucleases (DNases) universally induce irreversible cell death by fragmenting DNA in response to cell injury. All of the nine known cell death DNases are endonucleases. Despite that most of the DNase activity is used after cell death, a genetic inactivation of DNases provide protection of cells and tissues against DNA breaks induced by cytotoxic stimuli, and partially protect against tissue injury. Therefore, DNases act before the point-of-no-return in cell death, and can be potentially used as therapeutic targets for tissue protection against injury. Our studies identified two DNases, DNase I and EndoG, as being responsible for tubular epithelial toxicity during acute kidney injury induced by cisplatin, rhabdomyolysis or ischemia. However, inhibitors of DNases are not available. The purpose of this study was to identify DNase inhibitors, which might be used for mitigation of acute kidney injury.

Methodology & Theoretical Orientation: To identify DNase inhibitors, we have developed a high-throughput screening assay based on a proprietary fluorescent probe.

Findings: This assay allowed the identification of several new inhibitors of deoxyribonuclease I (DNase I), which were also active against two other DNases, endonucleases G (EndoG) and deoxyribonuclease II (DNase II). The DNase inhibitors were able to significantly protect kidney tubular epithelial cells in vitro and mouse kidneys in vivo against acute kidney toxicity induced by cisplatin, glycerol (rhabdomyolysis), or renal ischemia-reperfusion. The inhibitors showed no toxicity in vivo at 5x therapeutic doses.

Conclusion & Significance: DNases can be used as a therapeutic target for mitigation of toxic or hypoxic acute kidney injury. The identified DNase inhibitors or similar compounds have a great potential for tissue protection against toxic kidney failure. Considering that DNases are expressed and responsible for cell death in all tested cells, tissues and animal models, it is likely that the same compounds may be used for universal tissue protection against various injuries. 

 

Biography:

Dr. Sharp is a Forensic Pharmacologist. She has an M.Sci. degree in Pharmacology from the University of Glasgow, a Ph.D. in pharmacokinetics from the University of Dundee and Certificates in Civil and Criminal Law from the University of Cardiff. She specialises in drugs of abuse and the clearance of drugs from the body. She has prepared reports in many cases for a variety of legal firms in England, Wales, Ireland and Scotland She has been a research scientist for 8 years and has researched at the University of Cape Town in South Africa and the University of Dundee. Dr. Sharp is a co-director of the Glasgow Expert Witness Service Ltd. and is a registered expert witness with the Law Society of Scotland Directory of Expert Witnesses, a Professional Member of The Chartered Society of Forensic Sciences and a registered expert adviser on the National Crime Agency (NCA) database.

 

Abstract:

Dr. Sharp is a Forensic Pharmacologist. She has an M.Sci. degree in Pharmacology from the University of Glasgow, a Ph.D. in pharmacokinetics from the University of Dundee and Certificates in Civil and Criminal Law from the University of Cardiff. She specialises in drugs of abuse and the clearance of drugs from the body. She has prepared reports in many cases for a variety of legal firms in England, Wales, Ireland and Scotland She has been a research scientist for 8 years and has researched at the University of Cape Town in South Africa and the University of Dundee. Dr. Sharp is a co-director of the Glasgow Expert Witness Service Ltd. and is a registered expert witness with the Law Society of Scotland Directory of Expert Witnesses, a Professional Member of The Chartered Society of Forensic Sciences and a registered expert adviser on the National Crime Agency (NCA) database.

 

Biography:

Dr. Ming-Tsang Wu has completed his MD from Chung Shan Medical University in Taiwan and PhD from Harvard School of Public Health in the USA. He is a full professor in the Department of Public Health and the Director in Research Center for Environmental Medicine, Kaohsiung Medicine University, Taiwan. His major research interest is on the interactive effects of environmental and occupational exposures, genetic factors, and biomarkers on the health outcomes.

Abstract:

We are still exposed to low-dose melamine in daily-life environment, even after 2008 toxic milk food scandal. One of the main sources is the intake of melamine chemical from the migration of melamine-made tableware, when contacted with high-temperature soup/water. Our previous study has found that chronic low-dose melamine exposure is associated with the risk of renal stones in adults, but the data about the relationship between environmental melamine exposure and the risk of renal damage in humans is still lacking. In this talk, I will present our recent findings about that link from different susceptible populations and propose the mechanisms behind that.