Thomas Dick2018-10-15T18:33:49+00:00

Thomas Dick, Ph.D.

Associate Professor & Director of Antimicrobial Drug Discovery
Professor of Medicine

td367@njms.rutgers.edu   |   View CV
+1-973-854-3220

NEWS:

Recently published:  Aziz DB, Teo JWP, Dartois V, Dick T (2018) Teicoplanin – Tigecycline Combination Shows Synergy Against Mycobacterium abscessus. Front Microbiol 9: 932. PMI: 29867841

We are living in a perfect storm: resistance of bacteria against antibiotics is increasing and the drug discovery pipelines in industry are empty. There is an urgent medical need for the discovery and development of new antibacterials. To address this issue we established with our collaborators a fully enabled, academia based, drug discovery program comprising microbiology, structural biology, pharmacology and medicinal chemistry. Our focus is the identification of novel lead – target couples for lead optimization campaigns with the objective to deliver preclinical development compounds. The disease area of interest is lung disease caused by M. tuberculosis and Non-Tuberculous Mycobacteria (NTM), including M. abscessus and M. avium. Current tuberculosis projects include: next generation pyrazinamide and bedaquiline; microbiota metabolite indole propionic acid; DHFR inhibitors and membrane targeting alkyl indoles. NTM strategies include: repurposing (ribabutin, novel synergies); repositioning (oxazolidinones) and de novo drug discovery via various whole screen screens of TB active libraries, followed by parallel hit-to-lead and target deconvolution. In addition to carrying out drug discovery projects we are developing more predictive in vitro and ex vivo assays for NTM disease and a bacterial cell pharmacokinetic platform.

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Wu ML, Aziz DB, Dartois V, Dick T (2018) NTM drug discovery: status, gaps and the way forward. Drug Discov Today. PMI: 29635026

Yang X, Wedajo W, Yamada Y, Dahlroth SL, Neo JJ, Dick T, Chui WK (2018) 1,3,5-triazaspiro[5.5]undeca-2,4-dienes as selective Mycobacterium tuberculosis dihydrofolate reductase inhibitors with potent whole cell activity. Eur J Med Chem 144: 262-276. PMI: 29274493

Nyantakyi SA, Li M, Gopal P, Zimmerman M, Dartois V, Gengenbacher M, Dick T, Go ML (2018) Indolyl Azaspiroketal Mannich Bases Are Potent Antimycobacterial Agents with Selective Membrane Permeabilizing Effects and in Vivo Activity. J Med Chem 61: 5733-5750. PMI: 29894180

Joon S, Ragunathan P, Sundararaman L, Nartey W, Kundu S, Manimekalai MSS, Bogdanovic N, Dick T, Gruber G (2018) The NMR solution structure of Mycobacterium tuberculosis F-ATP synthase subunit epsilon provides new insight into energy coupling inside the rotary engine. FEBS J. PMI: 29360236

Chen C, Gardete S, Jansen RS, Shetty A, Dick T, Rhee KY, Dartois V (2018) Verapamil targets membrane energetics in Mycobacterium tuberculosis. Antimicrob Agents Chemother. PMI: 29463541

Aziz DB, Teo JWP, Dartois V, Dick T (2018) Teicoplanin – Tigecycline Combination Shows Synergy Against Mycobacterium abscessus. Front Microbiol 9: 932. PMI: 29867841

Yee M, Gopal P, Dick T (2017) Missense Mutations in the Unfoldase ClpC1 of the Caseinolytic Protease Complex Are Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 61. PMI: 27872068

Yang T, Moreira W, Nyantakyi SA, Chen H, Aziz DB, Go ML, Dick T (2017) Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure-Activity Relationships and Membrane Targeting Properties. J Med Chem. PMI: 28290692

Yamada Y, Dick T (2017) Mycobacterial Caseinolytic Protease Gene Regulator ClgR Is a Substrate of Caseinolytic Protease. mSphere 2. PMI: 28317028

Negatu DA, Liu JJJ, Zimmerman M, Kaya F, Dartois V, Aldrich CC, Gengenbacher M, Dick T (2017) Whole cell screen of fragment library identifies gut microbiota metabolite indole propionic acid as antitubercular. Antimicrob Agents Chemother. PMI: 29229639

Mukherjee D, Wu ML, Teo JWP, Dick T (2017) Vancomycin and clarithromycin show synergy against Mycobacterium abscessus in vitro. Antimicrob Agents Chemother. PMI: 28923867

Moreira W, Santhanakrishnan S, Ngan GJ, Low CB, Sangthongpitag K, Poulsen A, Dymock BW, Dick T (2017) Towards Selective Mycobacterial ClpP1P2 Inhibitors with Reduced Activity Against the Human Proteasome. Antimicrob Agents Chemother. PMI: 28193668

Moreira W, Santhanakrishnan S, Dymock BW, Dick T (2017) Bortezomib Warhead-Switch Confers Dual Activity against Mycobacterial Caseinolytic Protease and Proteasome and Selectivity against Human Proteasome. Front Microbiol 8: 746. PMI: 28496439

Low JL, Wu ML, Aziz DB, Laleu B, Dick T (2017) Screening of TB Actives for Activity against Nontuberculous Mycobacteria Delivers High Hit Rates. Front Microbiol 8: 1539. PMI: 28861054

Li M, Nyantakyi SA, Gopal P, Aziz DB, Dick T, Go ML (2017) Indolylalkyltriphenylphosphonium Analogues Are Membrane-Depolarizing Mycobactericidal Agents. ACS Med Chem Lett 8: 1165-1170. PMI: 29152049

Gopal P, Tasneen R, Yee M, Lanoix JP, Sarathy J, Rasic G, Li L, Dartois V, Nuermberger E, Dick T (2017) In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1. ACS Infect Dis. PMI: 28271875

Gopal P, Nartey W, Ragunathan P, Sarathy JP, Kaya F, Yee M, Setzer C, Manimekalai MSS, Dartois V, Gruber G, Dick T (2017) Pyrazinoic acid inhibits mycobacterial coenzyme A biosynthesis by binding to aspartate decarboxylase PanD. ACS Infect Dis. PMI: 28991455

Aziz DB, Low JL, Wu ML, Gengenbacher M, Teo JWP, Dartois V, Dick T (2017) Rifabutin Is Active against Mycobacterium abscessus Complex. Antimicrob Agents Chemother 61. PMI: 28396540

Wu ML, Gengenbacher M, Dick T (2016) Mild Nutrient Starvation Triggers the Development of a Small-Cell Survival Morphotype in Mycobacteria. Front Microbiol 7: 947. PMI: 27379076

Wu ML, Gengenbacher M, Chung JC, Chen SL, Mollenkopf HJ, Kaufmann SH, Dick T (2016) Developmental transcriptome of resting cell formation in Mycobacterium smegmatis. BMC Genomics 17: 837. PMI: 27784279

Wu ML, Chan CL, Dick T (2016) Rel Is Required for Morphogenesis of Resting Cells in Mycobacterium smegmatis. Front Microbiol 7: 1390. PMI: 27630635

Mukherjee D, Zou H, Liu S, Beuerman R, Dick T (2016) Membrane-targeting AM-0016 kills mycobacterial persisters and shows low propensity for resistance development. Future Microbiol 11: 643-650. PMI: 27158932

Moreira W, Lim JJ, Yeo SY, Ramanujulu PM, Dymock BW, Dick T (2016) Fragment-Based Whole Cell Screen Delivers Hits against M. tuberculosis and Non-tuberculous Mycobacteria. Front Microbiol 7: 1392. PMI: 27656168

Moreira W, Aziz DB, Dick T (2016) Boromycin Kills Mycobacterial Persisters without Detectable Resistance. Front Microbiol 7: 199. PMI: 26941723

Kundu S, Biukovic G, Gruber G, Dick T (2016) Bedaquiline Targets the epsilon Subunit of Mycobacterial F-ATP Synthase. Antimicrob Agents Chemother 60: 6977-6979. PMI: 27620476

Gopal P, Yee M, Sarathy J, Low JL, Sarathy JP, Kaya F, Dartois V, Gengenbacher M, Dick T (2016) Pyrazinamide Resistance Is Caused by Two Distinct Mechanisms: Prevention of Coenzyme A Depletion and Loss of Virulence Factor Synthesis. ACS Infect Dis 2: 616-626. PMI: 27759369