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)
Eduardo Cisneros de la Rosa, BS, Lead Research Specialist
Education: BS (Biochemistry), North Carolina State University
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)
Bianchi P, Fermo E, Lezon-Geyda K, van Beers EJ, Morton HD, Barcellini W, Glader B, Chonat S, Ravindranath Y, Newburger PE, Kollmar N, Despotovic JM, Verhovsek M, Sharma M, Kwiatkowski JL, Kuo KHM, Wlodarski MW, Yaish HM, Holzhauer S, Wang H, Kunz J, Addonizio K, Al-Sayegh H, London WB, Andres O, van Wijk R, Gallagher PG, Grace RFF. Genotype-Phenotype Correlation and Molecular Heterogeneity in Pyruvate Kinase Deficiency. Am J Hematol. 2020 May;95(5):472-482. PMID: 32043619
Zerra PE, Arthur CM, Chonat S, Maier CL, Mener A, Shin S, Allen JW, Baldwin WH, Cox C, Verkerke H, Jajosky RP, Tormey CA, Meeks SL and Stowell SR. Fc gamma receptors and complement component 3 facilitate anti-fVIII antibody formation. Front Physiol. Accepted. April 20, 2020
Thein SL, Pirenne F, Fasano, RM, Habibi A, Bartolucci, Chonat S, Hendrickson JE, Stowell SR. Hemolytic transfusion reactions in sickle cell disease: underappreciated and potentially fatal. Haematologica. 2020 Mar;105(3):539-544. PMID: 32029505
Arthur CM, Chonat S, Fasano R, Yee MEM, Josephson CD, Roback JD, Stowell SR. Examining the Role of Complement in Predicting, Preventing, and Treating Hemolytic Transfusion Reactions. Transfus Med Rev. 2019 Oct;33(4):217-224. PMID: 31679762
Graciaa S, Russell R, Chonat S. Complement mediated Hemolytic Anemia Secondary to Plasmodium Ovale Infection in a Child. J Pediatr Hematol Oncol. 2019 Oct;41(7):557-558. PMID: 31589179
Chonat S, Risinger M, Sakthivel H, Niss O, Rothman JA, Hsieh L, Chou ST, Kwiatkowski JL, Khandros E, Gorman MF, Wells DT, Maghathe T, Dagaonkar N, Seu KG, Zhang K, Zhang W, Kalfa TA. The Spectrum of SPTA1-Associated Hereditary Spherocytosis. Front Physiol. 2019 Jul 3;10:815. PMID: 31333484.
Chonat S, Arthur CM, Zerra PE, Maier CL, Jajosky RP, Yee MEM, Miller MJ, Josephson CD, Roback JD, Fasano R, Stowell SR. Challenges in preventing and treating hemolytic complications associated with red blood cell transfusion. Transfus Clin Biol. 2019 May;26(2):130-134. PMID: 30979566.
Fasano RM, Miller MJ, Chonat S, Stowell SR. Clinical presentation of delayed hemolytic transfusion reactions and hyperhemolysis in sickle cell disease. Transfus Clin Biol. 2019;26(2):94-98. PMID: 30837199
Mener A*, Patel SR*, Arthur CM, Chonat S, Wieland A, Santhanakrishnan M, Liu J, Maier CL, Jajosky RP, Girard-Pierce K, Bennett A, Zerra PE, Smith NH, Hendrickson JE, Stowell SR. Complement serves as a switch between CD4 T cell independent and dependent RBC antibody responses. JCI Insight 2018. Nov 15;3(22). pii: 121631. PMID: 30429364.
Chonat S, Quarmyne M, Bennett CM, Dean CL, Joiner CH, Fasano RM, and Stowell SR. Contribution of alternative complement pathway to delayed hemolytic transfusion reaction in sickle cell disease. Haematologica. 2018 Oct;103(10):e483-e485. PMID: 29794144.
Patel SR, Bennett A, Girard-Pierce K, Maier CL, Chonat S, Arthur CM, Zerra PE, Mener A, Stowell SR. Recipient priming to one RBC alloantigen directly enhances subsequent alloimmunization in mice. Blood Adv, 2018 Jan 23;2(2):105-115. PMID: 29365318
Chonat S, Chandrakasan S, Kalinyak KA, Ingala D, Gruppo R, Kalfa TA. Atypical haemolytic uraemic syndrome in a patient with sickle cell disease, successfully treated with eculizumab. Br J Haematol. 2016 Nov;175(4):744-747. PMID: 27870017.
Niss O, Chonat S, Dagaonkar N, Almansoori MO, Kerr K, Rogers Z, McGann P, Quarmyne M, Risinger M, Zhang K, Kalfa T. Genotype-phenotype correlations in hereditary elliptocytosis and hereditary pyropoikilocytosis. Blood Cells Mol Dis. 2016 Oct;61:4-9. PMID: 27667160.
NIH: R21EB028519 Trailblazer
Modeling atypical hemolytic uremic syndrome with hydrogel-based microvasculature-on-chip technologies
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
Ex-vivo studies of GBT-440