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College of Medicine: Department of Pharmacology and Toxicology

Alexei G. Basnakian, M.D., Ph.D., D.Sc.

Alexei Basnakian

Professor, Department of Pharmacology and Toxicology
Research Career Scientist, Central Ark Veteran’s Healthcare System
Phone: 501-352-2870
Fax: 501-686-8970
Email: basnakianalexeig@uams.edu

Education

  • M.D. – Sechenov Moscow Medical Academy, 1976
  • Ph.D. – USSR Academy of Medical Sciences, 1981
  • Postdoc – Harvard Medical School, 1988-1989

Research Interests

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.

Meet Dr. Basnakian’s Research Team

Recent Research Support

Current Research

  • VA Merit Review 2I01 BX002425-05A1 (PI)  (7/1/2019 – 6/30/2023)
    “DNase-targeted mitigation of acute kidney injury due to rhabdomyolysis”
  • USDA-AFRI 2017-07886 (Subcontract PI)  (04/01/18 – 03/31/22)
    “Environmental Risk Assessment of Carbon Nanomaterials Used as Plant Growth Regulators”
  • NIH/NIGMS P20 COBRE grant P20 GM109005 (Co-I in Core A, Director of Core B, Mentor)  (04/01/15 – 03/31/21)
    “Center for studies of host response to cancer therapy”
  • NIH/NIGMS P20 INBRE grant P20 GM103429-19 (Core Leader, Mentor) (04/01/20 – 03/31/25)
    “Center for studies of host response to cancer therapy”
  • NIH/NIGMS R01 grant (Other Significant Contributor) (9/1/20 – 8/31/25)
    “Preoperative exercise therapy for surgery triggered inflammation”
  • UAMS 1-2-3-Go grant (Co-Investigator) (04/1/21 – 03/31/22)
    “Bone-targeted Pyk2 inhibitor for prevention of bone fragility”
  • Research Mentor Award (Principal Investigator) (04/1/21 – 03/31/22)
  • Arkansas INBRE RD grant (Mentor) (5/1/20 – 10/30/22) “Development of novel thiazolo-androstenone antimelanoma agents”

Pending

  • NIH/NIGMS R01 grant (Co-Investigator) “Identification of DNA adducts from endogenous and exogenous sources at mutation hotspots”
  • NIH/NIGMS R15 grant  (Co-Investigator) “Novel pyrazole derivatives as antibacterial agents”

Completed Research

  • NIH/NIDDK ACCORD R01 grant DK096549-05 (Co-I)  (2011 – 2017)
    “Novel Serum and Urinary Biomarkers of Diabetic Kidney Disease”
  • FDA/Arkansas Research Alliance grant HHSF223201210189C (subaward PI)  (09/15/14 – 09/14/17)
    “Novel DNA damage-based technology for evaluation of graphene toxicity in vitro and in vivo”
  • 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”

Publications

  • Chambers SA, Newman M, Frangie MM, Savenka AV, Basnakian AG, Alam MA (2021) Antimelanoma activities of chimeric thiazole-androstenone derivatives. Royal Society Open Science, in press
  • Hansa Raj KC, Frangie MM, Khan MK, Gilmore DF, Shelton RS, Savenka AV, Basnakian AG, Smeltzer MS, Alam MA (2021) 4-4-(anilinomethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-ylbenzoic acid derivatives as potent anti-Gram-positive bacterial agents. Eur J Medicinal Chem, 113402. doi.org/10.1016/j.ejmech.2021.113402
  • Wang W, Li J, Tan J, Wang M, Yang J, Zhang Z, Li C, Basnakian AG, Tang HW, Perrimon N, Zhou Q (2021) Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response. Nat Commun, 12:476 doi.org/10.1038/s41467-020-20780-2
  • Fahmi T, Wang X, Zhdanov D, Islam I, Apostolov EO, Savenka AV, Basnakian AG (2020) DNase I induces other endonucleases in kidney tubular epithelial cells by its DNA-degrading activity. Int J Mol Sci: Mol Tox, 8665, 1-17, doi:10.3390/ijms21228665 
  • Delancey E, Allison D, Raj HKC, Gilmore DF, Fite T, Basnakian AG, Alam MA (2020) Synthesis of 4,4′-(4-formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid  Derivatives as Narrow Spectrum Antibiotics for Potential Treatment of Acinetobacter baumannii Infections. Antibiotics 2020, 9(10), 650; doi.org/10.3390/antibiotics9100650
  • Sadhukhan R, Leung JWC, Garg S, Krager KJ, Savenka AV, Basnakian AG, Pathak R (2020) Fractionated radiation suppresses endothelial Kruppel-like factor 2 pathway to a greater extent than by single exposure to the same total dose at early time points. Sci Rep, 2020 May 7;10(1):7734. PMCID: PMC7206069
  • Whitt J, Duke C, Sumlin A, Chambers A, Alnufaie R, Gilmore DF, Fite T, Basnakian AG, Alam MA. Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii. Molecules, 2019 May 29;24(11). PMID: 31146470 
  • Garg S, Sadhukhan R, Banerjee S, Savenka A, Basnakian AG, McHargue V, Wang J, Pawar S, Ghosh S, Ware J, Hauer-Jensen M, Pathak R (2019) Gamma-tocotrienol protects the intestine from radiation potentially by accelerating mesenchymal immune cell recovery. Antioxidants (Basel). 2019 Mar 6;8(3). pii: E57. [PMID: 30845647] 
  • Loukanov AR, Basnakian AG, Kawamura R, Hibiki U, Savenka AV, Fite T, Nakabayashi S (2018) Light-powered nanoconverter cytotoxic to breast cancer cells. J Phys Chem C 2018, 122, 14, 7916-7924
  • Basnakian AG, Braman N, Yin X, Kolomeychuk S, Apostolov EO (2017) Toxicological Analysis Using DNA Fragmentation. Encyclopedia of Analyt Chem, eds R.A. Meyers, John Wiley: Chichester. DOI: 10.1002/9780470027318.a9629. Published December 15 2017
  • Zhdanov DD, Wang X, Fahmi T, Fite T, Basnakian AG (2021) Truncated DNase I acts as dominant-negative inhibiting kidney cell death induced by cisplatin. Journal of Cellular and Molecular Medicine, submitted
  • Chambers SA, Newman M, Frangie MM, Savenka AV, Basnakian AG, Alam MA (2021) Antimelanoma activities of chimeric thiazole-androstenone derivatives. Chemistry and Medicinal Chemistry, submitted
  • Hansa Raj KC, Frangie MM, Khan MK, Gilmore DF, Shelton RS, Savenka AV, Basnakian AG, Smeltzer MS, Alam M A (2021) 4-4-(anilinomethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-ylbenzoic acid derivatives as potent anti-Gram-positive bacterial agents. Journal of Medicinal Chemistry, submitted
  • Wang W, Li J, Tan J, Wang M, Yang J, Zhang Z, Li C, Basnakian AG, Tang HW, Perrimon N, Zhou Q (2020) Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response. Nature Communications, in press
  • Fahmi T, Wang X, Zhdanov D, Islam I, Apostolov EO, Savenka AV, Basnakian AG (2020) DNase I induces other endonucleases in kidney tubular epithelial cells by its DNA-degrading activity. International Journal or Molecular Sciences, 2020, 8665, 1-17, doi:10.3390/ ijms21228665
  • Delancey E, Allison D, Raj HKC, Gilmore DF, Fite T, Basnakian AG, Alam MA (2020) Synthesis of 4,4′-(4-formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for Potential Treatment of Acinetobacter baumannii Antibiotics, 2020, 9(10), 650; https://doi.org/10.3390/antibiotics9100650
  • Chambers SA, Newman M, Frangie MM, Basnakian AG, Alam MA (2020) Antimelanoma activities of chimeric thiazole-androstenone derivatives. Bioorganic & Medicinal Chemistry Letters, submitted
  • Sadhukhan R, Leung JWC, Garg S, Krager KJ, Savenka AV, Basnakian AG, Pathak R (2020) Fractionated radiation suppresses endothelial Kruppel-like factor 2 pathway to a greater extent than by single exposure to the same total dose at early time points. Scientific Reports, 2020 May 7;10(1):7734. PMCID: PMC7206069
  • Whitt J, Duke C, Sumlin A, Chambers A, Alnufaie R, Gilmore DF, Fite T, Basnakian AG, Alam MA. Synthesis of Hydrazone Derivatives of 4-[4-Formyl-3-(2-oxochromen-3-yl)pyrazol-1-yl]benzoic acid as Potent Growth Inhibitors of Antibiotic-resistant Staphylococcus aureus and Acinetobacter baumannii. Molecules, 2019 May 29;24(11). PMID: 31146470
  • Garg S, Sadhukhan R, Banerjee S, Savenka A, Basnakian AG, McHargue V, Wang J, Pawar S, Ghosh S, Ware J, Hauer-Jensen M, Pathak R (2019) Gamma-tocotrienol protects the intestine from radiation potentially by accelerating mesenchymal immune cell recovery. Antioxidants (Basel). 2019 Mar 6;8(3). pii: E57. [PMID: 30845647]
  • Loukanov AR, Basnakian AG, Kawamura R, Hibiki U, Savenka AV, Fite T, Nakabayashi S (2018) Light-powered nanoconverter cytotoxic to breast cancer cells. J Phys Chem C2018, 122, 14, 7916-7924
  • Basnakian AG, Braman N, Yin X, Kolomeychuk S, Apostolov EO (2017) Toxicological Analysis Using DNA Fragmentation. Encyclopedia of Analyt Chem, eds R.A. Meyers, John Wiley: Chichester. DOI: 10.1002/9780470027318.a9629. Published December 15 2017
  • Basnakian AG, Braman N, Yin X, Kolomeychuk S, Apostolov EO. Toxicological Analysis Using DNA Fragmentation. Encyclopedia of Analyt Chem, in press.
  • Nedosekin DA, Fahmi T, Nima Z, Nolan J, Cai C, Dervishi E, Basnakian AG, Biris A, Zharov VP. Photoacoustic in vitro flow cytometry for nanomaterial research. Photoacoustics.  6:16-25, 2017. PMID: 28417068
  • Fahmi T, Branch D, Nima ZA, Jang DS, Savenka AV, Biris AS, Basnakian AG. Mechanism of graphene-induced cytotoxicity: Role of endonucleases. J Appl Toxicol.  (11):1325-1332, 2017. PMID: 28543094
  • Fil D, DeLoach A, Yadav S, Alkam D, MacNicol M, Singh A, Compadre CM, Goellner JJ, O’Brien CA, Fahmi T, Basnakian AG, Calingasan NY, Klessner JL, Beal FM, Peters OM, Metterville J, Brown RH Jr, Ling KKY, Rigo F, Ozdinler PH, Kiaei M. Mutant Profilin1 transgenic mice recapitulate cardinal features of motor neuron disease. Hum Mol Genet. 26(4):686-701, 2017. PMID: 28040732
  • Rogers LJ, Basnakian AG, Orloff MS, Ning B, Yao-Borengasser A, Raj V, Kadlubar S. 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine (PhIP) induces gene expression changes in JAK/STAT and MAPK pathways related to inflammation, diabetes and cancer. Nutr Metab (Lond).  13:54, 2016. PMID: 27547236
  • 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, JavadovS, Basnakian AG. Regulation of apoptotic endonucleases by EndoG. DNA Cell Biol.  34(5):316-26, 2015. PMID: 25849439
  • Barreto-Torres G, Hernandez JS, Jan S, Rodriquez-MunozA, Torres-Ramos CA, Basnakian AG, Javadov S. The benefician effects of AMP-kinase activation against oxidative stress are associated with prevention of PPARa/cyclophilin D interaction in cardiomyocytes. Am J Physiol Circ Heart.  308(7):H749-58, 2015. PMID: 25617357
  • Shah SV, Shukla AM, Bose C, Basnakian AG, Rajapurkar M. Recent advances in understanding the pathogenesis of atherosclerosis in CKD patients. J Ren Nutr.  25(2):205-8, 2015. PMID: 25556310
  • Jang DS, Penthala NR, Apostolov EO, Wang X, Fahmi T, Crooks PA, Basnakian AG. Novel high-throughput deoxyribonuclease 1 assay. J Biomol Screen. 20(2):202-11, 2015. PMID: 25326282
  • Jang DS, Penthala NR, Apostolov EO, Wang X, Crooks PA, Basnakian AG. DNA Cell Biol. 34(2):92-100, 2015. PMID: 25401220
  • 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

View Dr. Basnakian’s Publication List