22597-Johnson, Steven

Steven M. Johnson, PhD

Associate Professor of Biochemistry & Molecular Biology

Phone
(317) 274-2458
Address
635 Barnhill Drive
Medical Science, Room MS0013D
Indianapolis, IN 46202
PubMed:

Bio

Dr. Johnson has received industrial and academic training in research throughout the preclinical drug discovery and development process, from target identification, validation, and high-throughput screening, to in vitro and in vivo hit-to-lead optimization.  Dr. Johnson received his B.Sc. in Chemistry at the University of Victoria.  During his undergraduate studies, Dr. Johnson conducted industrial research internships at Boehringer Ingelheim, where he synthesized new drug candidates to target HIV reverse transcriptase and HCV NS3 protease.  These early studies sparked his enthusiasm for pursuing a career in medicinal chemistry and biomedical research.  Towards this goal, Dr. Johnson then ventured into the protein misfolding and neurodegeneration fields during his Ph.D. graduate studies with Prof. Jeffery Kelly at The Scripps Research Institute, where he synthesized molecules to study and selectively inhibit transthyretin amyloidogenesis.  Dr. Johnson continued with protein folding research during his postdoctoral studies with Prof. Arthur Horwich at Scripps/Yale, where he discovered inhibitors of the bacterial HSP60/10 chaperonin system (a.k.a. GroEL/ES) via high-throughput screening of a 700,000 compound library.  Afterwards, while at the University of Washington, Dr. Johnson developed inhibitors of calcium-dependent protein kinases from Toxoplasma gondii and Cryptosporidium parvum as part of a multi-institute collaboration focusing on the pharmacological optimization of antibiotics for toxoplasmosis and cryptosporidiosis.  Current research in Dr. Johnson’s independent lab expands on his interests and experiences in protein folding and misfolding to investigate targeting protein homeostasis (proteostasis) pathways to develop new infectious disease, neurodegeneration, and anti-cancer therapeutics.

Key Publications

                                                                                                                        

Godek, J.; Sivinski, J.; Watson, E.R.; Lebario, F.; Xu, W.; Stevens, M.; Zerio, C.J.; Ambrose, A.J.; Zhu, X.; Trindl, C.A.; Zhang, D.D.; Johnson, S.M.; Lander, G.C.; Chapman, E. Bis-sulfonamido-2-phenylbenzoxazoles Validate the GroES/EL Chaperone System as a Viable Antibiotic Target.. J. Am. Chem. Soc. 2024, 146 (30), 20845-20856Link to article

                                                                                                                         

Kim, H.R.; Byun, D.P.; Thakur, K.; Ritchie, J.; Xie, Y.; Holewinski, R.; Suazo, K.F.; Stevens, M.; Liechty, H.; Tagirasa, R.; Jing, Y.; Andresson, T.; Johnson, S.M.; Yoo, E. Discovery of a Tunable Heterocyclic Electrophile 4-Chloro-pyrazolopyridine That Defines a Unique Subset of Ligandable Cysteines. ACS Chem. Bio. 2024, 19 (5), 1082-1092Link to article

                                                                                                                         

Chitre, S.; Ray, A.M.; Stevens, M.; Doud, E.H.; Liechty, H.; Washburn, A.; Tepper, K.; Sivinski, J.; O'Hagan, H.M.; Georgiadis, M.M.; Chapman, E.; Johnson, S.M. Bis-aryl-α,β-unsaturated ketone (ABK) chaperonin inhibitors exhibit selective cytotoxicity to colorectal cancer cells that correlates with levels of aberrant HSP60 in the cytosol. Bioorg. Med. Chem. 2022, 1 (75), 117072Link to article

                                                                                                                         

Sivinski, J.; Ngo, D.; Zerio, C.J.; Ambrose, A.J.; Watson, E.R.; Kaneko, L.K.; Kostelic, M.M.; Stevens, M.; Ray, A.M.; Park, Y.; Wu. C.; Hoang, Q.Q.; Zhang, D.D.; Lander, G.C..; Johnson, S.M.; Chapman, E.  Allosteric differences dictate GroEL complementation of E. coli FASEB Journal 2022, 36 (3), e22198. Link to article

                                                                                                                        

Ray, A.M.; Salim, N.; Stevens M.; Chitre, S.; Abdeen, S.; Washburn, A.; Sivinski, J.; O’Hagan, H.M.; Chapman, E.; Johnson, S.M.  Exploiting the human HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer.  Bioorg. Med. Chem. 2021, Jun 15, 40:116129. Link to article.

                                                                                                                        

Stevens, M.; Howe, C.; Ray, A.M.; Washburn, A.; Chitre, S.; Sivinski, J.; Park, Y.; Hoang, Q.Q.; Chapman, E.; Johnson, S.  Analogs of nitrofuran antibiotics are potent GroEL/ES inhibitor pro-drugs.  Bioorg. Med. Chem. 2020, 28 (22). Link to article

                                                                                                                        

Ambrose, A.J.; Zerio, C.J.; Sivinski, J.; Schmidlin, C.J.; Shi, T.; Ross, A.B.; Widrick, K.J.; Johnson, S.M.; Zhang, D.D.; Chapman, E.  A high throughput substrate binding assay reveals hexachlorophene as an inhibitor of the ER-resident HSP70 chaperone GRP78.  Bioorg. Med. Chem. Lett. 2019, 29 (14), 1689-1693. Link to Article in PubMed

                                                                                                                        

Washburn, A.; Abdeen, S.; Ovechkina, Y.; Ray, A.M.; Stevens, M.; Chitre, S.; Sivinski, J.; Park, Y.; Johnson, J.; Hoang, Q.Q.; Chapman, E.; Parish, T.; Johnson, S.M. Dual-targeting GroEL/ES chaperonin and protein tyrosine phosphatase B (PtpB) inhibitors: A polypharmacology strategy for treating Mycobacterium tuberculosis infections. Bioorg. Med. Chem. Lett. 2019, 29 (13), 1665-1672. Link to Article in PubMed

                                                                                                                        

 

Stevens, M.; Abdeen, S.; Salim, N.; Ray, A.M.; Washburn, A.; Chitre, S.; Sivinski, J.; Park, Y.; Hoang, Q.Q.; Chapman, E.; Johnson, S.M. HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules. Bioorg. Med. Chem. Lett. 2019, 29 (9), 1106-1112. Link to Article in PubMed

                                                                                                                       

 

Kunkle, T.; Abdeen, S.; Salim, N.; Ray, A.M.; Stevens, M.; Ambrose, A.J.; Victorino, J.; Park, Y.; Hoang, Q.Q.; Chapman, E.; Johnson, S.M. Hydroxybiphenylamide GroEL/ES inhibitors are potent antibacterials against planktonic and biofilm forms of Staphylococcus aureus. J. Med. Chem. 2018, 61 (23), 10651-10664. Link to Article in PubMed

                                                                                                                       

Abdeen, S.; Kunkle, T.; Salim, N.; Ray, A.M.; Mammadova, N.; Summers, C.M.; Stevens, M.; Ambrose, A.J.; Park, Y.; Schultz, P.G.; Horwich, A.L.; Hoang, Q.; Chapman, E.; Johnson, S.M. Sulfonamido-2-arylbenzoxazole GroEL/ES Inhibitors as Potent Antibacterials against Methicillin-Resistant Staphylococcus aureus (MRSA). J. Med. Chem. 2018, 61 (16), 7345-7357. Link to Article in PubMed

                                                                                                                       

Connelly, S.; Mortenson, D.E.; Choi, S.; Wilson, I.A.; Powers, E.T.; Kelly, J.W.; Johnson, S.M.  Semi-quantitative models for identifying potent and selective transthyretin amyloidogenesis inhibitors.  Bioorg. Med. Chem. Lett.  2017, 27 (15), 3441-3449. Link to Article in PubMed

                                                                                                                       

Abdeen, S.; Salim, N.; Mammadova, N.; Summers, C.M.; Goldsmith-Pestana, K.; McMahon-Pratt, D.; Schultz, P.G.; Horwich, A.L.; Chapman, E.; Johnson, S.M.  Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness.  Bioorg. Med. Chem. Lett. 2016, 26 (21), 5247-5253. Link to Article in PubMed

                                                                                                                       

Abdeen, S.; Salim, N.; Mammadova, N.; Summers, C.; Frankson, R.; Ambrose, A.J.; Anderson, G.G.; Schultz, P.G.; Horwich, A.L.; Chapman, E.; Johnson, S.M.  GroEL/ES inhibitors as potential antibiotics.  Bioorg. Med. Chem. Lett. 2016, 26 (13), 3127-3134. Link to Article in PubMed

                                                                                                                       

Johnson, S.M.; Sharif, O.; Mak, P.A.; Wang, H.T.; Engels, I.H.; Brinker, A.; Schultz, P.; Horwich, A.L.; Chapman, E.  A biochemical screen for GroEL/GroES inhibitors.  Bioorg. Med. Chem. Lett. 2014, 24 (3), 786-789. Link to Article in PubMed


For a complete list of publications, visit PubMed

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