Backus, Keriann M.

Organic

Backus Keriann

Short Biography

Prof. Backus received her B.S. in Chemistry and B.A. in Latin American Studies from Brown University in 2007. As a 2007 Rhodes Scholar and an NIH Oxford Cambridge Scholar, she pursued her Ph.D. in the laboratories of Prof. Benjamin Davis (Oxford) and Prof. Clifton Barry (NIH, NIAID). Her doctoral research focused on the synthesis and application of trehalose-based chemical probes to label and image Mycobacterium tuberculosis. In 2012 Dr. Backus completed her doctorate and began an NIH postdoctoral fellowship at The Scripps Research Institute in the laboratory of Prof. Benjamin Cravatt. At TSRI she developed chemical proteomics platforms to conduct covalent fragment-based screening at cysteine and lysine residues proteome-wide. Prof. Backus is an Assistant Professor of Biological Chemistry at the David Geffen School of Medicine an Assistant Professor of Chemistry and Biochemistry at UCLA.

Research Interests

Small molecule and antibody modulators of the immune system have proven efficacious in the treatment of cancer, infectious diseases and autoimmune disorders. These successes underline the need for other immunomodulatory agents, in particular cell-penetrating small molecules, that can target proteins inaccessible to monoclonal antibodies. Combining chemical proteomics and activity-based protein profiling (ABPP), we synthesize new probes and develop new methods to study and manipulate the human immune system.

Honors & Awards

  • NIH Director’s New Innovator Award (2021)
  • David and Lucile Packard Foundation Fellowship (2020)
  • Kolin Endowed Chair (2019)
  • V Scholar Research Award (2019)
  • DARPA Young Faculty Award (2019)
  • Beckman Young Investigator (2019)
  • Ruth Kirschstein National Research Service Award Postdoctoral Fellowship (2013)
  • Rhodes Scholarship, Washington State and New College (2007)
  • NIH Oxford Cambridge Scholarship (2007)
  • Phi Beta Kappa, Rhode Island Chapter (2007)
  • USA Today Academic All-Star (2007)
  • National Merit Scholar (2003)

Representative Publications

  • A solid-phase compatible silane-based cleavable linker enables custom isobaric quantitative chemoproteomics. Burton, N.; Polasky, D.; Shikwanna, F.; Ofori, S.; Yan, T.; Geiszler, D.; da Veiga Leprevost, F.; Nesvizhskii, A.; Backus, K . ChemRxiv (2023). doi:10.26434/chemrxiv-2023-n8h29 This content is a preprint and has not been peer-reviewed. (link)
  • Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation-responsive mitochondrial redoxome.
    Yan T, Julio AR, Villanueva M, Jones AE, Ball AAB, Boatner LM, Turmon AC, Yen SL, Desai HS, Divakaruni AS, Backus KM. bioRxiv [Preprint]. 2023 Jan 31:2023.01.22.525042. doi: 10.1101/2023.01.22.525042. PMID: 36711448; PMCID: PMC9882296. (link)
  • Introduction to the themed collection on Covalent Drug Discovery. Backus KM, Pan Z, Jones LH. RSC Med Chem. 2022 Jul 14;13(8):893-894. doi: 10.1039/d2md90022j. PMID: 36092145; PMCID: PMC9384831. (link)
  • CysDB: A Human Cysteine Database based on Experimental Quantitative Chemoproteomics. Boatner, L., Palafox, M., Schweppe, D. & Backus, K.ChemRxiv (2022). doi:10.26434/chemrxiv-2022-w4h3t This content is a preprint and has not been peer-reviewed. (link)
  • SP3-FAIMS-Enabled High-Throughput Quantitative Profiling of the Cysteinome. Desai HS, Yan T, Backus KM. . Curr Protoc. 2022 Jul;2(7):e492. doi: 10.1002/cpz1.492. PMID: 35895291.; (link)
  • SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Desai HS, Yan T, Yu F, Sun AW, Villanueva M, Nesvizhskii AI, Backus KM. Mol Cell Proteomics. 2022 Apr;21(4):100218. doi: 10.1016/j.mcpro.2022.100218. Epub 2022 Feb 25. PMID: 35219905; PMCID: PMC9010637. (link)
  • Tunable heteroaromatic azoline thioethers (HATs) for cysteine profiling Tang KC, Maddox SM, Backus KM, Raj M. (2022) Chem. Sci., 13, 763-774. doi:10.1039/D1SC04139H; (link)
  • Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine Tang KC, Cao J, Boatner LM, Li L, Farhi J, Houk KN, Spangle J, Backus KM, Raj M. (2021) Angew Chem Int Ed Engl. 61(5):e202112107. doi: 10.1002/anie.202112107. PMID: 34762358; (link)
  • Enhancing Cysteine Chemoproteomic Coverage Through Systematic Assessment of Click Chemistry Product Fragmentation Yan, T., Palmer, A., Geiszler, D., Polansky, D., Armenta, E., Nesvizhskii, A., Backus, K. (2021) ChemRxiv. doi:10.33774/chemrxiv-2021-4b291; (link)
  • Photoaffinity labelling strategies for mapping the small molecule-protein interactome Burton NR, Kim P, Backus KM. (2021) Org Biomol Chem. Sep 22;19(36):7792-780923 doi:10.1039/d1ob01353j; (link)
  • New Approaches to Target RNA Binding Proteins Julio, AR, Backus KM. (2021) Current Opinion in Chemical Biology. Volume 62, June 2021, Pages 13-23 doi:10.1016/j.cbpa.2020.12.006; (link)
  • SP3-FAIMS Chemoproteomics for High Coverage Profiling of the Human Cysteinome Yan T, Desai HS, Boatner LM, Yen SL, Cao J, Palafox MF, Jami-Alahmadi Y, Backus K. (2021) ChemBioChem. doi:10.1101/2020.07.03.186007; ChemRxiv doi:10.26434/chemrxiv.13487364.v1 (link)
  • From Chemoproteomic-Detected Amino Acids to Genomic Coordinates: Insights into Precise Multi-omic Data Integration Palafox MF, Desai HS, Arboleda VA#, Backus KM# (2021) Molecular Systems Biology. 17:e9840. doi:10.15252/msb.20209840 ; first on bioRxiv. doi:10.1101/2020.07.03.186007; #co-corresponding author (link)
  • Suzuki–Miyaura cross-coupling for chemoproteomic applications Cao J, Armenta A, Boatner LM, Desai HS, Chan NJ, Castellón JO, Backus KM (2020) ChemRxiv.  doi:10.26434/chemrxiv.12055218.v1.(link)
  • Integrative x-ray structure and molecular modeling for the rationalization of procaspase-8 inhibitor potency and selectivity Xu JH, Eberhardt, J, Hill-Payne B, Eberhardt J, González-Páez GE, Castellón JO, Cravatt, BF, Forli S#, Wolan DW#, Backus KM#. (2020) ACS Chem Biol. doi: 10.1021/acschembio.0c00019.  bioRxiv 721951 doi: 10.1101/721951; #co-corresponding author.(link)
  • Opportunities and challenges for the development of covalent chemical immunomodulators Backus KM, Jian Cao, Sean Maddox, Bioorganic and Medicinal Chemistry. (2019) pii: S0968-0896(19)30222-6 (link)
  • Applications of Reactive Cysteine Profiling Backus KM, (2018) In: . Current Topics in Microbiology and Immunology. Springer, Berlin, Heidelberg (link)
  • Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer Bar-Peled L., Kemper EK, Suciu RM, Vinogradova EV, Backus KM, Horning BD, Paul TA, Ichu TA, Svensson RU, Olucha J, Chang MW, Kok BP, Zhu Z, Ihle NT, Dix MM, Jiang P, Hayward MM, Saez E, Shaw RJ, Cravatt BF, Cell. 171(3):696-709 (2017) doi: 10.1016/j.cell.2017.08.051 (link)
  • Proteome-wide assessment of lysine reactivity and ligandability Hacker, SM*#Backus, KM*#, Lazear, MR, Forli, S, Correia, B, Cravatt, BF#, Nature Chemistry (2017) *co-first authorship; #co-corresponding author (link)
  • Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases Guo, CJ, Chang, F-Y, Wyche, TP, Backus, KM, Acker, TM, Funabashi, M, Taketani, M, Donia, MS, Nayfach, S, Pollard, KS., Cravatt, BF, Craik, CS, Clardy, J, Voigt, CA, Fischbach, MA, Cell 168(3): 517-526 (2017) doi: 10.1016/j.cell.2016.12.021(link)
  • A Screen for Protein-Protein Interactions in Live Mycobacteria Reveals a Functional Link between the Virulence-Associated Lipid Transporter LprG and the Mycolyltransferase Antigen 85A Touchette, MH, Bai, L, Van Vlack, ER, Cognetta, AB, Previti, ML, Backus, KM, Martin, DW, Cravatt, BF, Seeliger, JC ACS. Infec. Dis. 3(5):336-348 (2017) doi: 10.1021/acsinfecdis.6b00179 (link)
  • Covalent Modifiers of the Vacuolar ATPase Chen YC, Backus KM, Merkulova M, Yang C, Brown D, Cravatt BF, Zhang C., J. Am. Chem. Soc. 139(2):639–642 (2017) doi: 10.1021/jacs.6b12511 (link)
  • Chemical proteomic profiling of human methyltransferases Horning, B, Suciu, M, Ghadiri, D, Ulanovskaya, O, Lum, K, Backus, K, Brown, S, Rosen, H, Cravatt, B, J. Am. Chem. Soc. 138(40):13335-13343 (2016) DOI: 10.1021/jacs.6b07830 (link)
  • Chemical proteomic map of dimethylfumarate-sensitive cysteines in primary human T cells Blewett, M, Xie, J, Zaro, B, Backus, KM, Altman, A, Teijaro, J, Cravatt, BF Science Signaling, 9(445):rs10 (2016) doi: 10.1126/scisignal.aaf7694 (link)
  • Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine Briggs, KJ, Koivunen, P, Cao, S, Backus, KM, Olenchock, BA, Patel H, Zhang, Q, Signoretti, S., Gerfen, GJ, Richardson, AL, Witkiewicz, AK, Cravatt, BF, Clardy, J, Kaelin, Jr, WG Cell 166(1):126-39 (2016) doi: 10.1016/j.cell.2016.05.042 (link)
  • Proteome-wide covalent ligand discovery in native biological systems Backus, KM*#, Correia, B*, Lum, K., Forli, S, Horning, B, González-Páez, GE, Chatterjee, S, Lanning, BR, Teijaro, JR, Olson, AJ, Wolan, DW, Cravatt, BF, Nature 534(7608):570-4 (2016) *co-first authorship; #co-corresponding author doi: 10.1038/nature18002 (link)
  • The Three Mycobacterium tuberculosis Antigen 85 Isoforms have Unique Substrates and Activities Determined by Non-active Site Regions Backus, KM, Dolan, M, Barry, Barry, CS, Joe, M, McPhie, P, Boshoff, HM, Lowary, TL, Davis, BG#, Barry, CE III#, J. Biol. Chem. 289(36):25041-53 (2014) #co-corresponding author  doi: 10.1074/jbc.M114.581579 (link)
  • ESI-MS Assay of M. tuberculosis Cell Wall Antigen 85 Enzymes Permits Substrate Profiling and Design of a Mechanism-Based Inhibitor Barry, CS, Backus, KM, Barry, CS III, Davis, BG, J. Am. Chem. Soc. 133(34):13232-5 (2011) doi: 10.1021/ja204249p (link)
  • Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis Backus, K.M., Boshoff, H., Barry, C.T., Boutureira, O., Patel, M., D’Hooge, F., Lee, S., Kapil, T., Via, LE, Barry, CE III#, Davis, BG#, Nat. Chem. Biol. 7(4): 228-235 (2011) #co-corresponding author doi: 10.1038/nchembio.539 (link)