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Richard E. Lee, PhD
Richard E. Lee, PhD

Richard E. Lee, PhD

Member, St. Jude Faculty

  • Endowed Chair in Medicinal Chemistry
  • Adjunct Professor, University of Tennessee Health Science Center



PhD – University of Newcastle-upon-Tyne, United Kingdom

Research Interests

  • Design, synthesis and development of novel antibiotic and chemotherapeutic agents
  • The discovery of new chemical probes using computational chemistry and biophysical screening strategies to explore disease biology
  • Development of innovative therapeutic approaches to tackle drug-resistant infections

Selected Publications

Wallace MJ, Dharuman S, Fernando DM, Reeve SM, Gee CT, Yao J, Griffith EC, Phelps GA, Wright WC, Elmore JM, Lee RB, Chen T, Lee RE. Discovery and Characterization of the Antimetabolite Action of Thioacetamide-Linked 1,2,3-Triazoles as Disruptors of Cysteine Biosynthesis in Gram-Negative Bacteria. ACS Infect Dis Jan 13, 2020. doi: 10.1021/acsinfecdis.9b00406. [Epub ahead of print]. PMID: 31887254.

Griffith EC, Zhao Y, Singh AP, Conlon BP, Tangallapally R, Shadrick WR, Liu J, Wallace MJ, Yang L, Elmore JM, Li Y, Zheng Z, Miller DJ, Cheramie MN, Lee RB, LaFleur MD, Lewis K, Lee RE. Ureadepsipeptides as ClpP Activators. ACS Infect Dis Nov 8;5(11):1915-1925, 2019. PMID: 31588734.

Iverson A, Meyer CJ, Vogel P, Waidyarachchi S, Das N, Bruhn DF, Poole A, Butler MM, Bowlin TL, Lee RE, Rosch JW. Efficacy of Aminomethyl Spectinomycins against Complex Upper Respiratory Tract Bacterial Infections. Antimicrob Agents Chemother Apr 25;63(5), 2019. PMID: 30858215.

Sharma LK, Subramanian C, Yun MK, Frank MW, White SW, Rock CO, Lee RE, Jackowski S. A therapeutic approach to pantothenate kinase associated neurodegeneration. Nat Commun Oct 23;9(1):4399, 2018. PMID: 30352999.

Cherian PT, Cheramie MN, Marreddy RKR, Fernando DM, Hurdle JG, Lee RE. New β-lactam - Tetramic acid hybrids show promising antibacterial activities. Bioorg Med Chem Lett Oct 1;28(18):3105-3112, 2018. PMID: 30097368.

Brown Gandt A, Griffith EC, Lister IM, Billings LL, Han A, Tangallapally R, Zhao Y, Singh AP, Lee RE, LaFleur MD. In Vivo and In Vitro Effects of a ClpP-Activating Antibiotic against Vancomycin-Resistant Enterococci. Antimicrob Agents Chemother Jul 27; 62(8), 2018. PMID: 29784838.

Griffith EC, Wallace MJ, Wu Y, Kumar G, Gajewski S, Jackson P, Phelps GA, Zheng Z, Rock CO, Lee RE, White SW. The Structural and Functional Basis for Recurring Sulfa Drug Resistance Mutations in Staphylococcus aureus Dihydropteroate Synthase. Front Microbiol Jul 17;9:1369, 2017. PMID: 30065703.

Liu J, Bruhn DF, Lee RB, Zheng Z, Janusic T, Scherbakov D, Scherman MS, Boshoff HI, Das S, Rakesh, Waidyarachchi SL, Brewer TA, Gracia B, Yang L, Bollinger J, Robertson GT, Meibohm B, Lenaerts AJ, Ainsa J, Böttger EC, Lee RE. Structure-Activity Relationships of Spectinamide Antituberculosis Agents: A Dissection of Ribosomal Inhibition and Native Efflux Avoidance Contributions. ACS Infect Dis Jan 13;3(1):72-88, 2017. PMID: 28081607.

Robertson GT, Scherman MS, Bruhn DF, Liu J, Hastings C, McNeil MR, Butler MM, Bowlin TL, Lee RB, Lee RE, Lenaerts AJ. Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models. J Antimicrob Chemother Mar 1;72(3):770-777, 2017. PMID: 27999020.

Zhao Y, Shadrick WR, Wallace MJ, Wu Y, Griffith EC, Qi J, Yun MK, White SW, Lee RE. Pterin-sulfa conjugates as dihydropteroate synthase inhibitors and antibacterial agents. Bioorg Med Chem Lett Aug 15;26(16):3950-4, 2016. PMID: 27423480.

Rakesh, Bruhn DF, Scherman MS, Singh AP, Yang L, Liu J, Lenaerts AJ, Lee RE. Synthesis and evaluation of pretomanid (PA-824) oxazolidinone hybrids. Bioorg Med Chem Lett Jan 15;26(2):388-391, 2016. PMID: 26711150.

Bruhn DF, Waidyarachchi SL, Madhura DB, Shcherbakov D, Zheng Z, Liu J, Abdelrahman YM, Singh AP, Duscha S, Rathi C, Lee RB, Belland RJ, Meibohm B, Rosch JW, Böttger EC, Lee RE. Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections. Sci Transl Med May 20;7(288):288ra75, 2015. PMID: 25995221

Show More

Hammoudeh DI, Daté M, Yun MK, Zhang W, Boyd VA, Viacava Follis A, Griffith E, Lee RE, Bashford D, White SW. Identification and Characterization of an Allosteric Inhibitory Site on Dihydropteroate Synthase. ACS Chem Biol 9(6):1294-302, 2014. PMID: 24650357.

Yun MK, Hoagland D, Kumar G, Waddell MB, Rock CO, Lee RE, White SW. The identification, analysis and structure-based development of novel inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Bioorg Med Chem Apr 1;22(7):2157-65, 2014.

Rakesh, Bruhn DF, Scherman MS, Woolhiser LK, Madhura DB, Maddox MM, Singh AP, Lee RB, Hurdle JG, McNeil MR, Lenaerts AJ, Meibohm B, Lee RE. Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis. PLoS One Feb 5;9(2):e87909, 2014. PMID: 24505329.

Lee RE, Hurdle JG, Liu J, Bruhn DF, Matt T, Scherman MS, Vaddady PK, Zheng Z, Qi J, Akbergenov R, Das S, Madhura DB, Rathi C, Trivedi A, Villellas C, Lee RB, Rakesh, Waidyarachchi SL, Sun D, McNeil MR, Ainsa JA, Boshoff HI, Gonzalez-Juarrero M, Meibohm B, Böttger EC, Lenaerts AJ. Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux. Nat Med Feb;20(2):152-8, 2014. PMID: 24464186.

North EJ, Jackson M, Lee RE. New Approaches to Target the Mycolic Acid Biosynthesis Pathway for the Development of Tuberculosis Therapeutics. Curr Pharm Des Nov 18, 2013. [Epub ahead of print] PMID: 24245756.

McCoy F, Darbandi R, Lee HC, Bharatham K, Moldoveanu T, Royappa G, Dodd K, Lin W, Chen SI, Tangallapally RP, Kurokawa M, Lee RE, Shelat A, Chen T, Green DR, Harris RA, Lin SH, Fissore RA, Colbran RJ, Nutt LK. Metabolic Activation of CaMKII by Coenzyme A. Mol Cell S1097-2765(13)00643-6, 2013. PMID: 24095281.

Hammoudeh DI, Zhao Y, White SW, Lee RE. Replacing sulfa drugs with novel DHPS inhibitors.Future Med Chem Jul;5(11):1331-40, 2013. PMID: 23859210.

Shen L, M Maddox M, Adhikari S, Bruhn DF, Kumar M, Lee RE, Hurdle JG, Lee RE, Sun D. Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents. J Antibiot (Tokyo). Jun;66(6):319-25, 2013. PMID: 23549356

Trivedi A, Lee RE, Meibohm B. Applications of pharmacometrics in the clinical development and pharmacotherapy of anti-infectives. Expert Rev Clin Pharmacol Mar;6(2):159-70, 2013. PMID: 23473593.

North EJ, Scherman MS, Bruhn DF, Scarborough JS, Maddox MM, Jones V, Grzegorzewicz A, Yang L, Hess T, Morisseau C, Jackson M, McNeil MR, Lee RE. Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties. Bioorg Med Chem Feb 26, 2013. PMID: 23498915.

Wu X, Cherian PT, Lee RE, Hurdle JG. The membrane as a target for controlling hypervirulent Clostridium difficile infections. J Antimicrob Chemother Apr;68(4):806-15, 2013. PMID: 23264511.

Rakesh, Bruhn D, Madhura DB, Maddox M, Lee RB, Trivedi A, Yang L, Scherman MS, Gilliland JC, Gruppo V, McNeil MR, Lenaerts AJ, Meibohm B, Lee RE. Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties. Bioorg Med Chem Oct 15;20(20):6063-72, 2012. PMID: 22995771.

Cherian PT, Yao J, Leonardi R, Maddox MM, Luna VA, Rock CO, Lee RE. Acyl-sulfamates target the essential glycerol-phosphate acyltransferase (PlsY) in Gram-positive bacteria. Bioorg Med ChemAug 15;20(16):4985-94, 2012. PMID: 22795901.

Zhao Y, Hammoudeh D, Yun MK, Qi J, White SW, Lee RE. Structure-based design of novel pyrimido[4,5-c]pyridazine derivatives as dihydropteroate synthase inhibitors with increased affinity. Chem Med Chem March 13, 2012.

Yun MK, Wu Y, Li Z, Zhao Y, Waddell MB, Ferreira AM, Lee RE, Bashford D, White SW. Catalysis and sulfa drug resistance in dihydropteroate synthase. Science 335(6072):1110-4, 2012.

Grzegorzewicz AE, Pham H, Gundi VA, Scherman MS, North EJ, Hess T, Jones V, Gruppo V, Born SE, Korduláková J, Chavadi SS, Morisseau C, Lenaerts AJ, Lee RE, McNeil MR, Jackson M. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol February 19, 2012.

Hurdle JG, Heathcott AE, Yang L, Yan B, Lee RE. Reutericyclin and related analogues kill stationary phase Clostridium difficile at achievable colonic concentrations. J Antimicrob Chemother June 1, 2011.

Hurdle JG, O'Neill AJ, Chopra I, Lee RE. Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat Rev Microbiol 9(1):62-75, 2011.

Budha NR, Lee RB, Hurdle JG, Lee RE, Meibohm B. A simple in vitro PK/PD model system to determine time-kill curves of drugs against Mycobacteria. Tuberculosis (Edinb) Sep;89(5):378-85, 2009.

Mahrous EA, Lee RB, Lee RE. Lipid profiling using two-dimensional heteronuclear single quantum coherence NMR. Methods Mol Biol 579:89-102, 2009.

Sun D, Xu H, Wijerathna SR, Dealwis C, Lee RE. Structure-Based Design, Synthesis, and Evaluation of 2'-(2-Hydroxyethyl)-2'-deoxyadenosine and the 5'-Diphosphate Derivative as Ribonucleotide Reductase Inhibitors. Chem Med Chem 2009 Oct;4(10):1649-56, 2009.

Hurdle JG, Yendapally R, Sun D, Lee RE. Evaluation of analogs of reutericyclin as prospective candidates for the treatment of staphylococcal skin infections. Antimicrob Agents Chemother Jul 6, 2009. [Epub ahead of print]. PMID: 19581456.

Zhao W, Hevener KE, White SW, Lee RE, Boyett JM. A Statistical Framework to Evaluate Virtual Screening. BMC Bioinformatics Jul 20;10:225, 2009.

Sun D, Scherman MS, Jones V, Hurdle JG, Woolhiser LK, Knudson SE, Lenaerts AJ, Slayden RA, McNeil MR, Lee RE. Discovery, Synthesis, and Biological Evaluation of Piperidinol analogs With Anti-tuberculosis Activity. Bioorg Med Chem May 15;17(10):3588-94, 2009.

Hevener K, Zhao W, Ball D, Babaoglu K, Qi J, White S, Lee RE. Validation of Molecular Docking Programs for Virtual Screening against Dihydropteroate Synthase. J Chem Inf Mod 49 (2), 444–460, 2009.

Rakesh, Sun D, Lee RB, Tangallapally R, Lee RE. Synthesis, Optimization and Structure-Activity Relationships of 3,5-Disubstituted Isoxazolines as New Anti-tuberculosis Agents. Eur J Med Chem Feb;44(2):460-72, 2009.

Aubry S, Lee RE, Mahrous EA, Small PL, Beachboard D, Kishi Y. Synthesis and Structure of Mycolactone E Isolated from Frog Mycobacterium. Org Lett 10(23), 5385–5388, 2008.

Grimes KD, Lu Y, Zhang Y-M, Luna VA, Hurdle JG, Carson EI, Qi J, Kudrimoti S, Rock CO, Lee RE. Novel Acylphosphate Mimics that Target PlsY, an Essential Acyltransferase in Gram-Positive Bacteria. Chem Med Chem 3:1936-45, 2008.

Hevener KE, Ball DM, Buolamwini JK, Lee RE. Quantitative structure–activity relationship studies on nitrofuranyl anti-tubercular agents. Bioorganic and Medicinal Chemistry Sep 1;16(17):8042-53, 2008.

Hurdle J, Lee RB, Budha N, Scherman M, Carson E, Qi J, Jianjun, Cho S, Lenaerts A, Franzblau S, Meibohm BM, Bernd, Lee RE. A microbiological assessment of novel nitrofuranylamides as anti-tuberculosis agents. Journal of Antimicrobial Chemotherapy  Nov;62(5):1037-45, 2008.

Last update: February 2020