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.
- Explore the mechanisms of how complement proteins interact and modulate hyperhemolysis and multi-organ damage in sickle cell disease
- Use of endothelialized microfluidic model to study the role of complement and other cellular proteins on endothelial dysfunction in hemolytic uremic syndrome
- Understand mechanisms of antibody-mediated RBC removal and systematically investigate the effect of hemolytic transfusion reaction in sickle cell disease
- Study of the rheology (deformations and flow) of RBCs in sickle cell disease and other blood disorders
- Testing of new drugs in sickle cell disease using novel in vivo and in vitro methods
- Various clinical research projects on thrombotic microangiopathies including atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria and thrombotic thrombocytopenic purpura
- Alexion (Site PI): A phase 2, open label study of ALXN1210 in Children and Adolescents with Paroxysmal Nocturnal Hemoglobinuria (NCT03406507)
- Amgen (Site PI): A Study Evaluating the Efficacy and Safety of ABP 959 Compared with Eculizumab in Adult Participants with Paroxysmal Nocturnal Hemoglobinuria (NCT03818607)
- Agios (Site PI): A Study to Evaluate Efficacy and Safety of AG-348 in regularly transfused (007) and Not Regularly Transfused (006) Adult Participants with Pyruvate Kinase Deficiency (NCT03548220)
- Agios (Site PI): Pyruvate Kinase Deficiency Global Longitudinal Registry (PEAK Registry) (NCT03481738)
- Apellis (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 (Site PI): Pyruvate Kinase Deficiency Global Longitudinal Registry Study AG348-C-008 (NCT03481738)
Lab Members
Jayre Jones, BS, Senior Research Specialist
Education: BS (Chemistry), Emory University
Email: jajone4@emory.edu
Group Members
Segun Adeagbo, Medical Student, Emory University School of Medicine
Sara Graciaa, CPNP, Pediatric ANP in Hematology, Children's Healthcare of Atlanta
Luke del Balzo, Emory University, 2017 - 2018, Medical Student, Augusta University, GA
Hannah Baratz, Emory University, 2018 - 2019, Clinical Research Coordinator, Memorial Sloan Kettering Cancer Center, NY
Arthur CM, Allen JWL, Verkerke H, Yoo J, Jajosky RP, Girard-Pierce K, Chonat S, Zerra P, Maier C, Rha J, Fasano R, Josephson CD, Roback JD, Stowell SR. Antigen density dictates RBC clearance, but not antigen modulation, following incompatible RBC transfusion in mice. Blood Adv. 2021 Jan 26;5(2):527-538.
Boscoe AN, Yan Y, Hedgeman E, van Beers EJ, Al-Samkari H, Barcellini W, Eber SW, Glader B, Taish HM, Chonat S et al. Comorbidities and complications in adults with pyruvate kinase deficiency. Eur J Haematol. 2020 Dec 28 [Epub ahead of print]
Niss O, Lorsbach RB, Berger M, Chonat S et al. Congenital dyserythropoietic anemia type I: First report from the Congenital Dyserythropoietic Anemia Registry of North America (CDAR). Blood Cells Mol Dis. 2020 Dec 24;87:102534
Raghunandan S, Josephson CD, Verkerke H, Linam WM, Zera PE, Ingram TC, Arthur CM, Stowell SR, Briones M, Chonat S. Complement Inhibition in Severe COVID-19 Acute Respiratory Distress Syndrome. Front. Pediatr. 2020 Nov 20;9(1):457-460
Chonat S, Mener A, Verkerke H, Stowell SR. Role of complement in alloimmunization and hyperhemolysis. Curr Opin Hematol. 2020 Nov;27(6):406-414.
Chonat S, Graciaa S, Shin HS, Newton JG, Quarmyne MO, Boudreaux J, Tang A, Zerra PE, Rollins MR, Josephson CD, Brown C, Joiner CH, Fasano RM, Stowell SR. Eculizumab for Complement Mediated Thrombotic Microangiopathy in Sickle Cell Disease. Haematologica. 2020 July 30;1059120:2887-2891.
Zerra PE, Arthur CM, Chonat S, Maier CL, Mener A, Shin S, Allen JWL, Baldwin WH, Cox C, Verkerke H, Jajosky RP, Tormey CA, Meeks SL, Stowell SR. Fc gamma receptors and complement component 3 facilitate anti-fVIII antibody formation. Front Immunol. 2020 Jun 9;11:905.
ASH Scholar Award
Complement-mediated acute lung injury in sickle cell disease: Novel Mechanisms and therapies
Role: PI
NIH: R21EB028519 Trailblazer
Modeling atypical hemolytic uremic syndrome with hydrogel-based microvasculature-on-chip technologies
Role: MPI
NIH: K12HD072245
Modeling complement-mediated acute lung injury in sickle cell mice
Role: Pediatric Scholar
Pediatrics and Pathology Pilot Grant Award
The role of complement in factor VIII inhibitor development
Role: MPI
Global Therapeutics
Ex-vivo studies of GBT-440
Role: Co-I