The NIH and Children's Hospital of Pittsburgh Foundation-funded lab of Thomas Diacovo, MD has active research programs in thrombosis and cell signaling.
In the former case, the lab focuses on the development of genetically engineered biological platforms that enable the in vivo study of human platelet-mediated hemostasis and thrombosis as well as therapies aimed at preventing platelet-vessel wall interactions that contribute to arterial thromboembolic events. In particular, the lab is interested in developing new therapies to prevent blood clots in neonates requiring a systemic-to-pulmonary artery shunt for palliation of single ventricle physiology.
Using these avatar models, novel microfluidic technologies, and blood samples from neonates with congenital heart disease, the lab was able to demonstrate the in vitro and in vivo efficacy of a new P2Y12 inhibitor (cangrelor) in reducing human platelet-mediated thrombus formation. Based on these findings, the lab successfully conducted a Phase 1 pharmacokinetic / pharmacodynamic study (Diacovo PI) in order to determine drug safety and dose to use in a phase 3 trial (Diacovo, PI) to assess the efficacy of cangrelor in preventing shunt thrombosis in neonates in the early postoperative period.
In addition to thrombosis research, the Diacovo Lab has been studying the role of class I phosphoinositide 3-kinases (PI3K) signaling pathway in inflammation and in hematological malignances. In fact, the group was the first to demonstrate that PI3Kgamma and PI3Kdelta can act as non-classical oncogenes by enabling leukemic transformation of T cell progenitors in the absence of the PTEN phosphatase tumor suppressor, and (2) it is possible to exploit the “addiction” of a hematological malignancy to specific PI3K isoforms, enabling the rational design of a PI3Kgamma/delta dual inhibitor. To this end, the lab has developed and patented such an inhibitor. A phase 1 trial is planned within the year.