Overview
Our lab’s research focuses on questions residing at the interface of red blood cell (RBC) physiology, transfusion medicine, and complement biology. We leverage the use of various tools including pre-clinical animal models, human samples and microfluidics to explore the cellular mechanisms and effects of complement dysregulation underlying hyperhemolysis, thrombotic microangiopathy and organ injury in various diseases. The overall goal is to translate the basic and translational research findings to improve the care of patients with blood disorders.
He is actively involved in research and advocacy through United States Thrombotic Microangiopathy consortium.
Research Projects
- Define how complement activation contributes to hemolysis, thromboinflammation, and multiorgan injury in sickle cell disease and other blood disorders.
- Identify the molecular and cellular pathways driving transplant-associated thrombotic microangiopathy (TA-TMA).
- Develop endothelialized microfluidic models to investigate complement-mediated endothelial dysfunction and microvascular injury in TMA.
- Study red blood cell deformability, adhesion, and flow in sickle cell disease and other red blood cell disorders.
- Evaluate novel complement-directed therapies using innovative in vitro and in vivo models of TMA and hemolytic disease.
- Conduct clinical and translational studies in complement-mediated TMA, atypical hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria, and other rare hematologic disorders.
Clinical Trials
- Agios (Site PI): Pyruvate Kinase Deficiency Global Longitudinal Registry (PEAK Registry) (NCT03481738)
- Apellis APL2‑PNH‑209 (Site PI): An Open-Label, Single-Arm, Phase 2 Study to Evaluate the Safety, Pharmacokinetics, and Biologic Activity of Pegcetacoplan in Pediatric Patients with Paroxysmal Nocturnal Hemoglobinuria (NCT03500549)
- Agios AG348-C-022 (Site-PI): A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Subjects With Pyruvate Kinase Deficiency Who Are Regularly Transfused, Followed by a 5-Year Open-label Extension Period
- Agios AG348-C-023 (Site-PI): A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Mitapivat in Pediatric Subjects With Pyruvate Kinase Deficiency Who Are Not Regularly Transfused, Followed by a 5-Year Open-label Extension Period
- Novartis CLNP023I12201 (Site-PI): A Phase 3 PK, Safety, Tolerability of Iptacopan in Pediatric Paroxysmal Nocturnal Hemoglobinuria (PNH) patients
- Neurocognitive Monitoring in Thrombotic Thrombocytopenic Purpura (Graciaa/Chonat- Investigator Initiated Study): This study determines the prevalence of neurologic morbidity in congenital and immune thrombotic thrombocytopenic purpura and evaluates interactions between platelets, complement, and von Willebrand factor to elucidate in vivo hemostatic mechanisms.
- US Pediatric Immune Thrombotic Thrombocytopenic Purpura (iTTP) Registry – (Chonat National PI): The objective is to identify clinical features, laboratory trends, risk factors, relapse patterns and treatment strategies predictive of morbidity and mortality in pediatric immune thrombotic thrombocytopenic purpura.
- Peach Bowl LegACy Fund Chonat (Co-I): This Phase II clinical trial evaluates prophylactic use of the lectin pathway inhibitor narsoplimab in children and young adults with transplant-associated TMA.
- International PNH Interest Group (IPIG) PNH Registry (Site PI): The aim of IPIG is to improve the care and treatment of patients with PNH by providing guidance, information and education to healthcare professionals.