Alexei G. Basnakian, M.D., Ph.D.
Professor, Department of Pharmacology and Toxicology
Research Career Scientist, Central Ark Veteran’s Healthcare System
Phone: (501) 352-2870
Fax: (501) 686-8970
M.D. – Sechenov Moscow Medical Academy, 1976
Ph.D. – USSR Academy of Medical Sciences, 1981
Postdoc – Harvard Medical School, 1988-1989
Cell death is commonly associated with the enzymatic fragmentation of DNA. Cells have excessive DNA-degrading power provided by the group of DNases/endonucleases which includes: DNase I, DNase II, caspase-activated DNase, endonuclease G, DNase gamma and several other enzymes. Sometimes these enzymes are called “apoptotic endonucleases,” however they participate in necrosis, mitotic catastrophe, autophagy and other modes of cell death. Other roles of the DNases include clean-up after cell death, removal of foreign DNA inside the cell, and cleavage of DNA circulating in blood. Normally, host cell DNA is protected against the DNases. However, during toxic cell injury or disease, genomic DNA becomes accessible to DNases due to the change of cellular homeostasis and increased permeability of membranes. We try to identify endonucleases, which participate in premortem DNA fragmentation in renal tubular epithelium during ischemic or toxic acute renal failure, in heart and brain during ischemia, and in cancer cells during chemotherapy. Our studies show that an inhibition or inactivation of DNases is protective against cell death in different models. Therefore, DNases can be used as tools or targets to either decrease tissue injury in various diseases, or selectively increase injury of cancer tissues. DNase inhibition can be achieved by specific chemical inhibitors, which were recently identified by our team.
Recent Research Support
VA Merit Review I01 BX002425-01 (PI) (08/01/14 – 09/30/18)
“New mechanistic therapies for myoglobinuric acute kidney injury”
FDA/Arkansas Research Alliance grant HHSF223201210189C (subaward PI) (10/01/13 – 09/30/15)
“Novel DNA damage-based technology for evaluation of graphene toxicity in vitro and in vivo”
NIH/NIDDK ACCORD R01 grant DK096549-05 (Co-I) (2011 – 2017)
“Novel Serum and Urinary Biomarkers of Diabetic Kidney Disease”
NIH/NIGMS P20 COBRE grant P20 GM109005 (Co-Director of Core B) (04/01/15 – 03/31/20)
“Center for studies of host response to cancer therapy”
Pepper Center pilot grant (PI) (10/01/14 – 09/30/15)
“Anti-aging role of apoptotic endonuclease”
NIH/NIDDK 5R01DK078908 (PI) (02/01/08 – 01/31/15)
“Premortem enzymatic DNA damage in kidney injury”
NIH/NCRR INBRE (DNA Damage and Toxicology Core Leader) (05/01/10 – 03/31/15)
“Partnership for Biomedical Research in Arkansas”
VA Merit Review – Deployment Health Research Initiative (PI) (2009 – 2014)
“Novel endonuclease-targeted approaches to nephroprotection”
DOD TATRC (Subcontract PI) (08/01/11 – 07/31/15)
“Using advanced functional nanomaterials to fight cancer”
UAMS TRI Pilot Grant (PI) (2012 – 2014)
“Clinical testing of the novel carbamylated HDL assay”
Medical Research Endowment Award (PI) (2013 – 2014)
“Novel antisense ODN NIRF drug for prevention of kidney failure”
FDA/Arkansas Research Alliance Grant (PI) (2013 – 2014)
“Novel DNA fragmentation-based technology for evaluation of graphene toxicity in vitro and in vivo”
NIH/NIA R21AR053967-01A2 Subcontract (PI) (2010 – 2012)
“The role of endonuclease G in nuclear apoptosis of atrophying skeletal muscle”
NIH/NHLBI R21 HL087405-01A1 (PI) (2008 – 2011)
“LDL isoforms in kidney-related atherosclerosis”
Veteran Administration VA Merit Review Award (PI) (2005 – 2009)
“ROS/Endonuclease-Mediated DNA Damage in Deployment-Related Tissue Injury”
Rogers LJ, Basnakian AG, Orloff MS, Ning B, Yao-Borengasser A, Raj V, Kadlubar S. Exposure of adipocyte cultures to 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) results in gene expression changes. Nutrition and Metabolism, 2016 (in press).
Zhdanov DD, Fahmi T, Wang X, Apostolov EO, Sokolov NN, Javadov S, Basnakian AG. Regulation of apoptotic endonucleases by EndoG. DNA Cell Biol. 34, 5, 316-326, 2015 (PMID: 25849439) Cover page publication.
Jang D, Penthala N, Apostolov EO, Wang X, Crooks P, Basnakian AG. Novel Cytoprotective Inhibitors for Endonuclease G. DNA Cell Biol. 34, 2, 1-9, 2015 (PMID: 25401220).
Jang D, Penthala N, Apostolov EO, Wang X, Crooks P, Basnakian AG. Novel high-throughput deoxyribonuclease 1 assay. J Biomol Screening. 20, 2, 202-211, 2015 (PMID: 25326282).
Barreto-Torres G, Hernandez JS, Jang S, Rodríguez-Muñoz A, Torres-Ramos CA, Basnakian AG, Javadov S. The beneficial effects of AMP-kinase activation against oxidative stress are associated with prevention of PPARα/cyclophilin D interaction in cardiomyocytes. Am J Physiol Heart. 308, 7, H749-H758, 2015 (PMID: 25617357).
Miousse IR, Chalbot MC, Aykin-Burns N, Singleton T, Wang X, Basnakian AG, Kavouras I, Koturbash I. Epigenetic alterations induced by ambient particulate matter in mouse macrophages. Environ Mol Mutagen. 55, 5, 428-35, 2014 (PMID: 24535919).
Nima ZA, Mahmood M, Xu Y, Mustafa T, Watanabe F, Nedosekin DA, Juratli MA, Fahmi T, Galanzha EI, Nolan J, Basnakian AG, Zharov VP, Biris AS. Circulating cancer cell identification by functionalized silver-gold nanorods with super-enhanced SERS and photothermal resonances. Scientific Reports. 9; 4:4752, 2014 (PMID: 24810323).
Singh M, Odeniyi DT, Savenka A, Fite T, Apostolov EO, Wangila GW, Walker RB, Basnakian AG. Protective effects of Zinc-N-acetylcysteine on rat kidney during cold storage. Am J Physiol Renal. 305, 7, F1022-D1030, 2013 (PMID: 23825076).
Apostolov EO, Ok E, Burns S, Nawaz S, Savenka A, Shah SV, Basnakian AG. Carbamylated-oxidized LDL: pro-atherosclerotic effects on endothelial cells and macrophages. J Atherosc Thrombos. 20, 12, 878-892, 2013 (PMID: 24067603).
Akrawinthawong K, Shaw MK, Kachener J, Apostolov EO, Basnakian AG, Shah SV, Tilak J, McCullough PA. Urine catalytic iron and neutrophil gelatinase-associated lipocalin as companion early markers of acute kidney injury after cardiac surgery: a prospective pilot study. Cardiorenal Med. 3, 1, 7-16, 2013 (PMID: 23946721).
Galanzha EI, Shashkov E, Sarimollaoglu M, Beenken KE, Basnakian AG, Shirtliff ME, Kim JW, Smeltzer MS, Zharov VP. In vivo magnetic enrichment, photoacoustic diagnosis and photothermal purging of infected blood using multifunctional gold and magnetic nanoparticles. PLoS One. 7(9):e45557, 2012 (PMID: 23049814).
Apostolov EO, Basnakian AG, Ok E, Shah SV. Carbamylated low-density lipoprotein: nontraditional risk factor for cardiovascular events in patients with chronic kidney disease. J Ren Nutr. 22(1):134-8, 2012 (PMID: 2200430).
Prantner D, Sikes JD, Hennings L, Savenka AV, Basnakian AG, Nagarajan UM. Interferon regulatory transciption factor 3 protects mice from uterine horn pathology during Chlamydia muridarum genital infection. Infect Immun. 79(10):3922-33, 2011 (PMID: 21788382).