Dr. Jason D. Salter

The People of OyaGen

Dr. Jason Salter, Senior Scientist

Jason Salter

As a senior scientist at OyaGen, Inc. Jason’s is a key contributor to multiple aspects of screening and mechanistic projects at OyaGen. As a postdoctoral researcher at the University of Rochester, he focused on the biophysical and structural characterization of human antiretroviral cytidine deaminase APOBEC3G (A3G) and the HIV-1 auxiliary protein, Viral infectivity factor (Vif) which targets A3G for proteasomal degradation. While full-length A3G has been recalcitrant to crystallization, he utilized a variety of structural and biophysical analyses to glean insight into domain architecture and oligomeric properties of this potent antiretroviral protein, including small angle X-ray scattering (SAXS), size-exclusion chromatography, dynamic light scattering and analytical ultracentrifugation; these studies led to two publications that detailed the size, shape, and self-associative properties of A3G. In a second research project spanning his graduate and postdoctoral positions he investigated the thermodynamics of the interaction between HIV-1 Vif and human E3 ubiquitin ligase binding partner, Cullin5 . Vif is a substrate receptor for an E3 ubiquitin ligase complex that targets A3G for proteasomal degradation. He developed novel recombinant expression and purification methods to produce milligram quantities of Vif-E3 ubiquitin ligase complexes comprising Elongin B, Elongin C, Cullin5, and CBFβ for isothermal titration calorimetry (ITC) experiments important of assessing protein-protein interaction. His primary focus as a Senior Scientist at OyaGen has been the development and implementation of small molecule screens using both cell-based and purified protein-based assays to identify probes that disrupt protein-protein interactions critical to HIV or Ebola lifecycle. He has also developed fluorescence anisotropy methodology in-house to validate small molecule hits that disrupt Vif multimerization as on-target that were discovered in primary screens; he has continued to use ITC and surface plasmon resonance techniques to evaluate hit compound binding to target proteins. He is driven by continued interest in exploring the structure-function relationship of proteins involved in human health and the development of molecular probes that alter protein function.

Publications

Bennett RP, Finch CL, Postnikova EN, Stewart RA, Cai Y, Yu S, Liang J, Dyall J, Salter JD, Smith HC, Kuhn JH. A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures. Viruses2020 Dec 31;13(1)doi: 10.3390/v13010052. PubMed PMID: 33396288; PubMed Central PMCID: PMC7824103.
 
Salter JD, Smith HC. Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands. Trends Biochem Sci2018 Aug;43(8):606-622doi: 10.1016/j.tibs.2018.04.013. Epub 2018 May 23. Review. PubMed PMID: 29803538; PubMed Central PMCID: PMC6073885.
 
Bennett RP, Salter JD, Smith HC. A New Class of Antiretroviral Enabling Innate Immunity by Protecting APOBEC3 from HIV Vif-Dependent Degradation. Trends Mol Med2018 May;24(5):507-520doi: 10.1016/j.molmed.2018.03.004. Epub 2018 Mar 30. Review. PubMed PMID: 29609878; PubMed Central PMCID: PMC7362305.
 
Bennett RP, Stewart RA, Hogan PA, Ptak RG, Mankowski MK, Hartman TL, Buckheit RW Jr, Snyder BA, Salter JD, Morales GA, Smith HC. An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation. Antiviral Res2016 Dec;136:51-59doi: 10.1016/j.antiviral.2016.11.001. Epub 2016 Nov 5. PubMed PMID: 27825797; PubMed Central PMCID: PMC5125868.
 
Polevoda B, McDougall WM, Bennett RP, Salter JD, Smith HC. Structural and functional assessment of APOBEC3G macromolecular complexes. Methods2016 Sep 1;107:10-22doi: 10.1016/j.ymeth.2016.03.006. Epub 2016 Mar 14. PubMed PMID: 26988126; PubMed Central PMCID: PMC5014647.
 
Salter JD, Bennett RP, Smith HC. The APOBEC Protein Family: United by Structure, Divergent in Function. Trends Biochem Sci2016 Jul;41(7):578-594doi: 10.1016/j.tibs.2016.05.001. Epub 2016 Jun 6. Review. PubMed PMID: 27283515; PubMed Central PMCID: PMC4930407.
 
Polevoda B, McDougall WM, Tun BN, Cheung M, Salter JD, Friedman AE, Smith HC. RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates. Nucleic Acids Res2015 Oct 30;43(19):9434-45doi: 10.1093/nar/gkv970. Epub 2015 Sep 30. PubMed PMID: 26424853; PubMed Central PMCID: PMC4627094.
 
Salter JD, Morales GA, Smith HC. Structural insights for HIV-1 therapeutic strategies targeting Vif. Trends Biochem Sci2014 Sep;39(9):373-80doi: 10.1016/j.tibs.2014.07.001. Epub 2014 Aug 12. Review. PubMed PMID: 25124760; PubMed Central PMCID: PMC4511815.
 
Prohaska KM, Bennett RP, Salter JD, Smith HC. The multifaceted roles of RNA binding in APOBEC cytidine deaminase functions. Wiley Interdiscip Rev RNA2014 Jul-Aug;5(4):493-508doi: 10.1002/wrna.1226. Epub 2014 Mar 24. Review. PubMed PMID: 24664896; PubMed Central PMCID: PMC4062598.
 
Salter JD, Lippa GM, Belashov IA, Wedekind JE. Core-binding factor β increases the affinity between human Cullin 5 and HIV-1 Vif within an E3 ligase complex. Biochemistry2012 Nov 6;51(44):8702-4doi: 10.1021/bi301244z. Epub 2012 Oct 25. PubMed PMID: 23098073; PubMed Central PMCID: PMC3598157.
 
Salter JD, Krucinska J, Raina J, Smith HC, Wedekind JE. A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self-association that has implications for anti-HIV function. Biochemistry2009 Nov 17;48(45):10685-7doi: 10.1021/bi901642c. PubMed PMID: 19839647; PubMed Central PMCID: PMC2783380.
 
Bennett RP, Salter JD, Liu X, Wedekind JE, Smith HC. APOBEC3G subunits self-associate via the C-terminal deaminase domain. J Biol Chem2008 Nov 28;283(48):33329-36doi: 10.1074/jbc.M803726200. Epub 2008 Oct 8. PubMed PMID: 18842592; PubMed Central PMCID: PMC2586250.
 
MacElrevey C, Salter JD, Krucinska J, Wedekind JE. Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme. RNA2008 Aug;14(8):1600-16doi: 10.1261/rna.1055308. Epub 2008 Jul 2. PubMed PMID: 18596253; PubMed Central PMCID: PMC2491461.
 
Hoffman DL, Salter JD, Brookes PS. Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: implications for hypoxic cell signaling. Am J Physiol Heart Circ Physiol2007 Jan;292(1):H101-8doi: 10.1152/ajpheart.00699.2006. Epub 2006 Sep 8. PubMed PMID: 16963616.
 
Wedekind JE, Gillilan R, Janda A, Krucinska J, Salter JD, Bennett RP, Raina J, Smith HC. Nanostructures of APOBEC3G support a hierarchical assembly model of high molecular mass ribonucleoprotein particles from dimeric subunits. J Biol Chem2006 Dec 15;281(50):38122-6doi: 10.1074/jbc.C600253200. Epub 2006 Oct 31. PubMed PMID: 17079235; PubMed Central PMCID: PMC1847398.
 
Gunter KK, Aschner M, Miller LM, Eliseev R, Salter J, Anderson K, Gunter TE. Determining the oxidation states of manganese in NT2 cells and cultured astrocytes. Neurobiol Aging2006 Dec;27(12):1816-26doi: 10.1016/j.neurobiolaging.2005.10.003. Epub 2005 Nov 14. PubMed PMID: 16290323.
 
Salter J, Krucinska J, Alam S, Grum-Tokars V, Wedekind JE. Water in the active site of an all-RNA hairpin ribozyme and effects of Gua8 base variants on the geometry of phosphoryl transfer. Biochemistry2006 Jan 24;45(3):686-700doi: 10.1021/bi051887k. PubMed PMID: 16411744; PubMed Central PMCID: PMC2546605.
 
Gunter KK, Aschner M, Miller LM, Eliseev R, Salter J, Anderson K, Hammond S, Gunter TE. Determining the oxidation states of manganese in PC12 and nerve growth factor-induced PC12 cells. Free Radic Biol Med2005 Jul 15;39(2):164-81doi: 10.1016/j.freeradbiomed.2005.03.004. Epub 2005 Mar 31. PubMed PMID: 15964508.
 
Gunter TE, Yule DI, Gunter KK, Eliseev RA, Salter JDCalcium and mitochondria. FEBS Lett2004 Jun 1;567(1):96-102doi: 10.1016/j.febslet.2004.03.071. Review. PubMed PMID: 15165900.
 
Hoffmann MM, Salter JDMeasuring P-V-T Phase Behavior with a Variable Volume View Cell. Journal of chemical education. 2004 March81(3):411.
 
Gunter TE, Miller LM, Gavin CE, Eliseev R, Salter J, Buntinas L, Alexandrov A, Hammond S, Gunter KK. Determination of the oxidation states of manganese in brain, liver, and heart mitochondria. J Neurochem2004 Jan;88(2):266-80doi: 10.1046/j.1471-4159.2003.02122.x. PubMed PMID: 14690515.
 
Eliseev RA, Salter JD, Gunter KK, Gunter TE. Bcl-2 and tBid proteins counter-regulate mitochondrial potassium transport. Biochim Biophys Acta2003 Apr 18;1604(1):1-5doi: 10.1016/s0005-2728(03)00005-7. PubMed PMID: 12686415.