Dr. Le’s research focuses on understanding the cellular and molecular mechanisms that control immune responses, with a particular emphasis on how nucleotide metabolism governs and contributes to immune activation and response. Nucleotide metabolism interconnects to many biological pathways. Therefore, cells face choices about achieving their metabolic goals, whether to replicate their DNA during proliferation or siphon nucleosides and nucleotides into the extracellular space for cell communication via the purinergic receptors. There is interest in thoroughly understanding how immune cells direct their nucleotide metabolism to balance their nucleotide pools and elucidating the immunologic consequences when pools become imbalanced due to stress and disease. This is particularly intriguing, given that nucleotide metabolism is influenced not only by substrate availability but also by signaling pathways elicited by the very nucleoside and nucleotides themselves.
Abt ER, Le TM, Dann AM, Capri JR, Poddar S, Lok V, Li L, Liang K, Creech AL, Rashid K, Kim W, Wu N, Cui J, Cho A, Lee HR, Rosser EW, Link JM, Czernin J, Wu T, Damoiseaux R, Dawson DW, Donahue TR, Radu CG. Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells. Cell Rep. 2022 Jan 11;38(2):110236. doi:10.1016/j.celrep.2021.110236. PMID: 35021095; PMCID: PMC8893345.
Liang K, Abt ER, Le TM, Cho A, Dann AM, Cui J, Li L, Rashid K, Creech AL, Wei L, Ghukasyan R, Rosser EW, Wu N, Carlucci G, Czernin J, Donahue TR, Radu CG. STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging. Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2105390118. doi: 10.1073/pnas.2105390118. PMID: 34480004; PMCID: PMC8433573.
Stuparu AD, Capri JR, Meyer CAL, Le TM, Evans-Axelsson SL, Current K, Lennox M, Mona CE, Fendler WP, Calais J, Eiber M, Dahlbom M, Czernin J, Radu CG, Lückerath K, Slavik R. Mechanisms of Resistance to Prostate-Specific Membrane Antigen-Targeted Radioligand Therapy in a Mouse Model of Prostate Cancer. J Nucl Med. 2021 Jul 1;62(7):989-995. doi: 10.2967/jnumed.120.256263. PMID: 33277393.
Abt ER, Rosser EW, Durst MA, Lok V, Poddar S, Le TM, Cho A, Kim W, Wei L, Song J, Capri JR, Xu S, Wu N, Slavik R, Jung ME, Damoiseaux R, Czernin J, Donahue TR, Lavie A, Radu CG. Metabolic Modifier Screen Reveals Secondary Targets of Protein Kinase Inhibitors within Nucleotide Metabolism. Cell Chem Biol. 2020 Feb 20;27(2):197-205.e6. doi: 10.1016/j.chembiol.2019.10.012. PMID: 31734178; PMCID: PMC7035983.
Le TM, Poddar S, Capri JR, Abt ER, Kim W, Wei L, Uong NT, Cheng CM, Braas D, Nikanjam M, Rix P, Merkurjev D, Zaretsky J, Kornblum HI, Ribas A, Herschman HR, Whitelegge J, Faull KF, Donahue TR, Czernin J, Radu CG. ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways. Nat Commun. 2017 Aug 14;8(1):241. PubMed PMID: 28808226; PubMed Central PMCID: PMC5556071.