Education & Training
- Medical School – McGill University, Montreal, Canada – MD
- Internship – Baylor College of Medicine - Pediatrics
- Residency – Baylor College of Medicine - Pediatrics
- Fellowship – Children’s Hospital Boston – Neonatal-Perinatal Medicine
NIH Grants: R01
Dr. Diacovo’s research endeavors stem from his clinical interest in hemostasis and thrombosis, and in particular understanding and preventing thrombotic events in neonates undergoing complex cardiac repair for cyanotic heart lesions. This involves the interrogation of key adhesion and signaling pathways in platelets from pre and post-operative neonatal cardiac patients using low volume microfluidic technologies, state-of-the-art genetic and bioenergetic approaches, and a proprietary animal model that permits the in vivo study of human platelet mediated hemostasis and thrombosis. Based on this work, a phase I PK /PD study has now been completed for the P2Y12 inhibitor cangrelor for use in the prevention of shunt thrombosis in neonates requiring palliation with a systemic-to-pulmonary artery shunt. Plans are underway for a phase 3 national / international trial.
Another focus of Dr. Diacovo’s laboratory is elucidating the role that class I PI3Ks play in innate and adaptive immune responses. His group discovered that it is possible to protect against and reduce the extent of tissue injury associated with an acute inflammatory response by selectively targeting the PI3K isoforms gamma and delta. He also made the seminal observation that (i) PI3Kgamma and PI3Kdelta can function as non-classical oncogenes, supporting the development and survival of T cell acute lymphoblastic leukemia (T-ALL), and (ii) that it is feasible to therapeutically exploit the requirement of this leukemia to these PI3K isoforms, enabling the rational design of a PI3Kgamma/delta dual inhibitor for use in the treatment of childhood leukemia. Work is currently focused on further characterization of a novel dual PI3K gamma/delta inhibitor developed by the Diacovo and Landry labs at Columbia University, as well as understanding potential mechanisms of drug resistance.
- Akat KM, Lee YA, Hurley A, Morozov P, Max KE, Brown M, Bogardus K, Sopeyin A, Hildner K, Diacovo TG, Neurath MF, Borggrefe M, Tuschl T. Detection of circulating extracellular mRNAs by modified small-RNA-sequencing analysis. JCI Insight. 2019 Apr 11;5. PMID:30973829
- Max KEA, Bertram K, Akat KM, Bogardus KA, Li J, Morozov P, Ben-Dov IZ, Li X, Weiss ZR, Azizian A, Sopeyin A, Diacovo TG, Adamidi C, Williams Z, Tuschl T. Human plasma and serum extracellular small RNA reference profiles and their clinical utility. Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):E5334-E5343. doi: 10.1073/pnas.1714397115. Epub 2018 May 18. PubMed PMID: 29777089.
- Kaza EA, Egalka MC, Zhou H, Chen J, Evans D, Prats J, Li R, Diamond SL, Vincent JA, Bacha EA, Diacovo TG. P2Y(12) Receptor Function and Response to Cangrelor in Neonates With Cyanotic Congenital Heart Disease. JACC Basic Transl Sci. 2017 Aug;2(4):465-476. doi: 10.1016/j.jacbts.2017.04.002. Epub 2017 Jul 19. PubMed PMID: 29057376; PubMed Central PMCID: PMC5646421.
- Efimenko E, Davé UP, Lebedeva IV, Shen Y, Sanchez-Quintero MJ, Diolaiti D, Kung A, Lannutti BJ, Chen J, Realubit R, Niatsetskaya Z, Ten V, Karan C, Chen X, Califano A, Diacovo TG. PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature. Mol Cancer Ther. 2017 Oct;16(10):2069-2082. doi: 10.1158/1535-7163.MCT-17-0141. Epub 2017 Jul 17. PubMed PMID: 28716817; PubMed Central PMCID: PMC6075817.
- Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32. doi: 10.1056/NEJMoa1509981. Epub 2015 Dec 7. PubMed PMID: 26641137; PubMed Central PMCID: PMC4862586.
- Chen J, Zhou H, Diacovo A, Zheng XL, Emsley J, Diacovo TG. Exploiting the kinetic interplay between GPIbα-VWF binding interfaces to regulate hemostasis and thrombosis. Blood. 2014 Dec 11;124(25):3799-807. doi: 10.1182/blood-2014-04-569392. Epub 2014 Oct 7. PubMed PMID: 25293780; PubMed Central PMCID: PMC4263987.
- Li J, Vootukuri S, Shang Y, Negri A, Jiang JK, Nedelman M, Diacovo TG, Filizola M, Thomas CJ, Coller BS. RUC-4: a novel αIIbβ3 antagonist for prehospital therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2321-9. doi: 10.1161/ATVBAHA.114.303724. Epub 2014 Aug 21. PubMed PMID: 25147334; PubMed Central PMCID: PMC4180209.
- Santulli G, Wronska A, Uryu K, Diacovo TG, Gao M, Marx SO, Kitajewski J, Chilton JM, Akat KM, Tuschl T, Marks AR, Totary-Jain H. A selective microRNA-based strategy inhibits restenosis while preserving endothelial function. J Clin Invest. 2014 Sep;124(9):4102-14. doi: 10.1172/JCI76069. Epub 2014 Aug 18. PubMed PMID: 25133430; PubMed Central PMCID: PMC4153706.
- Wang W, Lindsey JP, Chen J, Diacovo TG, King MR. Analysis of early thrombus dynamics in a humanized mouse laser injury model. Biorheology. 2014;51(1):3-14. doi: 10.3233/BIR-130648. PubMed PMID: 24598379.
- Subramaniam P, Whye D, Efimenko E, Chen J, Tosello V, De Keersmaecker K, Kashishian A, Thompson MA, Castillo M, Cordon-Cardo C, Davé UP, Ferrando A, Lannutti B, Diacovo TG. Targeting non-classical oncogenes for therapy in T-ALL. Cancer Cell 2012. 21; 459-472. PMID: 22516257