Caius Radu, MD
Dr. Caius Radu's research seeks to advance the understanding of how fundamental biological processes are affected by the intersection of metabolic and signal transduction networks. His team hopes to leverage this knowledge towards the development of new diagnostic and therapeutic approaches that will improve patient care. To conduct this work, Radu utilizes the essential components of an integrated research program that were established in his lab, including state-of-the-art instrumentation for both Positron Emission Tomography (PET) and Mass Spectrometry assays. These efforts are done in collaboration with an interdisciplinary team of investigators at UCLA and other institutions, with expertise in metabolism, cancer biology, signal transduction, structural biology, radiochemistry, molecular imaging and medicinal chemistry. Recent discoveries made in Radu's lab include the uncovering of a new role for the nucleoside salvage pathway in hematopoiesis, identifying a metabolic kinase as a new therapeutic target in leukemia, and the development of new PET probes for nucleotide metabolism (several of which have been successfully translated to the clinic). His team also identified a clinical candidate compound with low nanomolar affinity and oral bioavailability that emerged from their discovery of novel small molecule inhibitors of deoxycytidine kinase, a finding which provides potential indications in leukemia and selected solid tumors.
Kim W, Le TM, Wei L, Poddar S, Bazzy J, Wang X, Uong NT, Abt ER, Capri JR, Austin WR, Van Valkenburgh JS, Steele D, Gipson RM, Slavik R, Cabebe AE, Taechariyakul T, Yaghoubi SS, Lee JT, Sadeghi S, Lavie A, Faull KF, Witte ON, Donahue TR, Phelps ME, Herschman HR, Herrmann K, Czernin J, Radu CG. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity. Proc Natl Acad Sci U S A. 2016 Mar 28. pii: 201524212. [Epub ahead of print]
Nathanson DA, Armijo AL, Tom M, Li Z, Dimitrova E, Austin WR, Nomme J, Campbell DO, Ta L, Le TM, Lee JT, Darvish R, Gordin A, Wei L, Liao HI, Wilks M, Martin C, Sadeghi S, Murphy JM, Boulos N, Phelps ME, Faull KF, Herschman HR, Jung ME, Czernin J, Lavie A, Radu CG. Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication. J Exp Med. 2014 Mar 10;211(3):473-86. doi: 10.1084/jem.20131738. Epub 2014 Feb 24.
Murphy JM, Armijo AL, Nomme J, Lee CH, Smith QA, Li Z, Campbell DO, Liao HI, Nathanson DA, Austin WR, Lee JT, Darvish R, Wei L, Wang J, Su Y, Damoiseaux R, Sadeghi S, Phelps ME, Herschman HR, Czernin J, Alexandrova AN, Jung ME, Lavie A, Radu CG. Development of new deoxycytidine kinase inhibitors and noninvasive in vivo evaluation using positron emission tomography. J Med Chem. 2013 Sep 12;56(17):6696-708. doi: 10.1021/jm400457y. Epub 2013 Aug 15.
Nomme J, Murphy JM, Su Y, Sansone ND, Armijo AL, Olson ST, Radu C, Lavie A. Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules. Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):68-78. doi: 10.1107/S1399004713025030. Epub 2013 Dec 24.
Austin WR, Armijo AL, Campbell DO, Singh AS, Hsieh T, Nathanson D, Herschman HR, Phelps ME, Witte ON, Czernin J, Radu CG. Nucleoside salvage pathway kinases regulate hematopoiesis by linking nucleotide metabolism with replication stress. J Exp Med. 2012 Nov 19;209(12):2215-28. doi: 10.1084/jem.20121061. Epub 2012 Nov 12.