Bradley Backes, PhD
Associate Professor
Medicine
School of Medicine

Grants and Projects

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• Developing UPR inhibitory KIRAs into oral antidiabetic beta cell-sparing drugs, NIH, 2014-2023
• Targeting epithelial cells to treat pulmonary fibrosis, NIH, 2012-2018
• IRE1 alpha inhibitors for Retinal Degenerative Diseases, NIH, 2015-2017
• IRE1 alpha inhibitors for type 2 diabetes, NIH, 2015-2017
• Inflammasome Inhibitors for Type 2 Diabetes, NIH, 2012-2014
• Developing UPR Modulators as Novel Therapeutics for Neurodegeneration, NIH, 2011-2012
• Cytoprotective Effects of UPR Modulators in ER Stress-Challenged beta-Cells, NIH, 2009-2010

Publications (33)

Top publication keywords:
Multienzyme ComplexesCombinatorial Chemistry TechniquesEndoribonucleasesDipeptidyl-Peptidase IV InhibitorsProtein Kinase InhibitorsFibrinolysinReceptors, GlucocorticoidMifepristoneEnzyme InhibitorsPyrrolidinesEndoplasmic Reticulum StressPhenethylaminesPeptide LibraryChemistry, PharmaceuticalCysteine Endopeptidases

• IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis.
  American journal of physiology. Lung cellular and molecular physiology 2022 Auyeung VC, Downey MS, Thamsen M, Wenger TA, Backes BJ, Sheppard D, Papa FR
• ATP-competitive partial antagonists of the IRE1α RNase segregate outputs of the UPR.
  Nature chemical biology 2021 Feldman HC, Ghosh R, Auyeung VC, Mueller JL, Kim JH, Potter ZE, Vidadala VN, Perera BGK, Olivier A, Backes BJ, Zikherman J, Papa FR, Maly DJ
• A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome.
  The Journal of experimental medicine 2020 Deng Z, Chong Z, Law CS, Mukai K, Ho FO, Martinu T, Backes BJ, Eckalbar WL, Taguchi T, Shum AK
• Targeting Adaptive IRE1α Signaling and PLK2 in Multiple Myeloma: Possible Anti-Tumor Mechanisms of KIRA8 and Nilotinib.
  International journal of molecular sciences 2020 Yamashita Y, Morita S, Hosoi H, Kobata H, Kishimoto S, Ishibashi T, Mishima H, Kinoshita A, Backes BJ, Yoshiura KI, Papa FR, Sonoki T, Tamura S
• Parallel Signaling through IRE1α and PERK Regulates Pancreatic Neuroendocrine Tumor Growth and Survival.
  Cancer research 2019 Moore PC, Qi JY, Thamsen M, Ghosh R, Peng J, Gliedt MJ, Meza-Acevedo R, Warren RE, Hiniker A, Kim GE, Maly DJ, Backes BJ, Papa FR, Oakes SA

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• Development of a Chemical Toolset for Studying the Paralog-Specific Function of IRE1.
  ACS chemical biology 2019 Feldman HC, Vidadala VN, Potter ZE, Papa FR, Backes BJ, Maly DJ
• Small molecule inhibition of IRE1α kinase/RNase has anti-fibrotic effects in the lung.
  PloS one 2019 Thamsen M, Ghosh R, Auyeung VC, Brumwell A, Chapman HA, Backes BJ, Perara G, Maly DJ, Sheppard D, Papa FR
• Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis.
  The Journal of clinical investigation 2017 Wei Y, Kim TJ, Peng DH, Duan D, Gibbons DL, Yamauchi M, Jackson JR, Le Saux CJ, Calhoun C, Peters J, Derynck R, Backes BJ, Chapman HA
• Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes.
  Cell metabolism 2017 Morita S, Villalta SA, Feldman HC, Register AC, Rosenthal W, Hoffmann-Petersen IT, Mehdizadeh M, Ghosh R, Wang L, Colon-Negron K, Meza-Acevedo R, Backes BJ, Maly DJ, Bluestone JA, Papa FR
• Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes.
  Cell metabolism 2017 Morita S, Villalta SA, Feldman HC, Register AC, Rosenthal W, Hoffmann-Petersen IT, Mehdizadeh M, Ghosh R, Wang L, Colon-Negron K, Meza-Acevedo R, Backes BJ, Maly DJ, Bluestone JA, Papa FR
• Structural and Functional Analysis of the Allosteric Inhibition of IRE1α with ATP-Competitive Ligands.
  ACS chemical biology 2016 Feldman HC, Tong M, Wang L, Meza-Acevedo R, Gobillot TA, Lebedev I, Gliedt MJ, Hari SB, Mitra AK, Backes BJ, Papa FR, Seeliger MA, Maly DJ
• Allosteric inhibition of the IRE1α RNase preserves cell viability and function during endoplasmic reticulum stress.
  Cell 2014 Ghosh R, Wang L, Wang ES, Perera BG, Igbaria A, Morita S, Prado K, Thamsen M, Caswell D, Macias H, Weiberth KF, Gliedt MJ, Alavi MV, Hari SB, Mitra AK, Bhhatarai B, Schürer SC, Snapp EL, Gould DB, …
• Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors.
  Nature chemical biology 2012 Wang L, Perera BG, Hari SB, Bhhatarai B, Backes BJ, Seeliger MA, Schürer SC, Oakes SA, Papa FR, Maly DJ
• IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress.
  Cell metabolism 2012 Lerner AG, Upton JP, Praveen PV, Ghosh R, Nakagawa Y, Igbaria A, Shen S, Nguyen V, Backes BJ, Heiman M, Heintz N, Greengard P, Hui S, Tang Q, Trusina A, Oakes SA, Papa FR
• IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates.
  Cell 2009 Han D, Lerner AG, Vande Walle L, Upton JP, Xu W, Hagen A, Backes BJ, Oakes SA, Papa FR
• Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin-mediated angioedema.
  British journal of pharmacology 2007 Fryer RM, Segreti J, Banfor PN, Widomski DL, Backes BJ, Lin CW, Ballaron SJ, Cox BF, Trevillyan JM, Reinhart GA, von Geldern TW
• Synthesis of C-11 modified mifepristone analog libraries.
  Molecular diversity 2007 Hamilton GL, Backes BJ
• Discovery and structure-activity relationships of piperidinone- and piperidine-constrained phenethylamines as novel, potent, and selective dipeptidyl peptidase IV inhibitors.
  Journal of medicinal chemistry 2007 Pei Z, Li X, von Geldern TW, Longenecker K, Pireh D, Stewart KD, Backes BJ, Lai C, Lubben TH, Ballaron SJ, Beno DW, Kempf-Grote AJ, Sham HL, Trevillyan JM
• Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.
  Bioorganic & medicinal chemistry letters 2007 Backes BJ, Longenecker K, Hamilton GL, Stewart K, Lai C, Kopecka H, von Geldern TW, Madar DJ, Pei Z, Lubben TH, Zinker BA, Tian Z, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Kempf-Grote AJ, Black-…
• Discovery of ((4R,5S)-5-amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
  Journal of medicinal chemistry 2006 Pei Z, Li X, von Geldern TW, Madar DJ, Longenecker K, Yong H, Lubben TH, Stewart KD, Zinker BA, Backes BJ, Judd AS, Mulhern M, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Reinhart GA, Fryer RM, …
• Parallel strategies for the preparation and selection of liver-targeted glucocorticoid receptor antagonists.
  Bioorganic & medicinal chemistry letters 2006 Backes BJ, Hamilton GL, Nguyen P, Wilcox D, Fung S, Wang J, Grynfarb M, Goos-Nilsson A, Jacobson PB, von Geldern TW
• A strategy to profile prime and non-prime proteolytic substrate specificity.
  Bioorganic & medicinal chemistry letters 2005 Petrassi HM, Williams JA, Li J, Tumanut C, Ek J, Nakai T, Masick B, Backes BJ, Harris JL
• Purifying the masses: integrating prepurification quality control, high-throughput LC/MS purification, and compound plating to feed high-throughput screening.
  Journal of combinatorial chemistry 2005 Isbell JJ, Zhou Y, Guintu C, Rynd M, Jiang S, Petrov D, Micklash K, Mainquist J, Ek J, Chang J, Weselak M, Backes BJ, Brailsford A, Shave D
• Biochemical characterization of prostasin, a channel activating protease.
  Biochemical and biophysical research communications 2004 Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ, Harris JL
• Activity profile of dust mite allergen extract using substrate libraries and functional proteomic microarrays.
  Chemistry & biology 2004 Harris J, Mason DE, Li J, Burdick KW, Backes BJ, Chen T, Shipway A, Van Heeke G, Gough L, Ghaemmaghami A, Shakib F, Debaene F, Winssinger N
• Biochemical analysis of the 20 S proteasome of Trypanosoma brucei.
  The Journal of biological chemistry 2003 Wang CC, Bozdech Z, Liu CL, Shipway A, Backes BJ, Harris JL, Bogyo M
• Expedient solid-phase synthesis of fluorogenic protease substrates using the 7-amino-4-carbamoylmethylcoumarin (ACC) fluorophore.
  The Journal of organic chemistry 2002 Maly DJ, Leonetti F, Backes BJ, Dauber DS, Harris JL, Craik CS, Ellman JA
• Substrate specificity of the human proteasome.
  Chemistry & biology 2001 Harris JL, Alper PB, Li J, Rechsteiner M, Backes BJ
• From Split-Pool Libraries to Spatially Addressable Microarrays and Its Application to Functional Proteomic Profiling.
  Angewandte Chemie (International ed. in English) 2001 Winssinger N, Harris JL, Backes BJ, Schultz PG
• Definition of the extended substrate specificity determinants for beta-tryptases I and II.
  The Journal of biological chemistry 2001 Harris JL, Niles A, Burdick K, Maffitt M, Backes BJ, Ellman JA, Kuntz I, Haak-Frendscho M, Craik CS
• Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries.
  Proceedings of the National Academy of Sciences of the United States of America 2000 Harris JL, Backes BJ, Leonetti F, Mahrus S, Ellman JA, Craik CS
• Synthesis of positional-scanning libraries of fluorogenic peptide substrates to define the extended substrate specificity of plasmin and thrombin.
  Nature biotechnology 2000 Backes BJ, Harris JL, Leonetti F, Craik CS, Ellman JA
• Solid support linker strategies.
  Current opinion in chemical biology 1997 Backes BJ, Ellman JA