Overview
Our lab is focused on research surrounding the immune response to factor VIII in patients with hemophilia A and on how the diversity of the B cell epitopes in the response influence effectiveness of treatment. We have on-going basic and translational studies focused on how factor VIII is initially seen by the immune system and how the B cell response develops over time. Current translational projects are addressing naïve and memory B cells in patients with hemophilia A receiving factor VIII therapy.
Seema Patel, PhD, Assistant Professor of Pediatrics
Education: BS, University of Georgia; Graduate and Post-doctoral Studies, Emory University
Email: srpate2@emory.edu
W. Hunter Baldwin, BS, Research Specialist
Education: BS (Biology), Virginia Tech
Email: hunterbaldwin@emory.edu
Courtney Cox, MS, Research Specialist
Education: BS (Cellular and Molecular Biology), University of Hawaii; MS (Microbiology with specialty in Virology), University of Hawaii
Email: courtney.cox@emory.edu
Batsuli G, Zimowski KL, Tickle K, Meeks SL and Sidonio RF JR. Immune tolerance induction in paediatric patients with haemophilia A and inhibitors receiving Emicizumab prophylaxis. Haemophilia. 2019; 25(5): 789-796. PMID: 31373431.
Meeks SL and Herzog RW. The national blueprint for future basic and translational research to understand factor VIII immunogenicity: NHLBI State of the Science Workshop on factor VIII inhibitors. Haemophilia. 2019; 25(4): 595-602. PMID: 31329368.
Batsuli G, Ito J, Mercer R, Baldwin WH, Cox C, Parker ET, Healey JF, Lollar P and Meeks SL. Anti-C1 domain antibodies that accelerate factor VIII clearance contribute to antibody pathogenicity in a murine hemophilia A model. J Thromb Haemost. 2018. 16(9): 1779-1788. PBMID: 29981270.
Zerra PE, Cox C, Baldwin WH, Patel SR, Arthur CM, Lollar P, Meeks SL and Stowell SR. Marginal zone B cells are critical to factor VIII inhibitor formation in mice with hemophilia A. Blood. 2017. 130(23): 2559-2568. PMID: 28978569.
Meeks SL and Batsuli G. Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches. Hematology Am Soc Hematol Educ Program. 2016; 2016(1): 657-662. PMID 27912543.
Zakas PM, Brown HC, Knight K, Meeks SL, Spencer HT, Gaucher EA, and Doering CB. Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction. Nat Biotechnol. 2016 Sep 26. PMID: 27669166.
Batsuli G, Deng W, Healey JF, Parker ET, Baldwin WH, Cox C, Nguyen B, Kahle J, Konigs C, Li R, Lollar P, and Meeks SL. High-affinity, non-inhibitory, pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors. Blood. 2016; 128:2055-67. PMID: 27381905.
Eubanks J, Baldwin WH, Markovitz R, Parker ET, Cox C, Kempton CL, and Meeks SL. A subset of high titer anti-factor VIII A2 domain antibodies are responsive to treatment with factor VIII. Blood. 2016; 127(16):2028-34. PMID: 26825708.
Kempton CL, Meeks SL. Toward optimal therapy for inhibitors in hemophilia. Blood. 2014 Nov 27;124(23):3365-72. PubMed PMID: 25428222.
Sevy AM, Healey JF, Deng W, Spiegel PC, Meeks SL, Li R. Epitope mapping of inhibitory antibodies targeting the C2 domain of coagulation factor VIII by hydrogen-deuterium exchange mass spectrometry. J Thromb Haemost. 2013 Dec;11(12):2128-36. PubMed PMID: 24152306; PubMed Central PMCID: PMC3947443.
Meeks SL, Chapman RL, Kempton C, Dunn AL. Late immune tolerance induction in haemophilia A patients. Haemophilia. 2013 May;19(3):445-8. PubMed PMID: 23294063.
Doshi BS, Gangadharan B, Doering CB, Meeks SL. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition. PLoS One. 2012;7(10):e48172. PubMed PMID: 23144741; PubMed Central PMCID: PMC3483154.
Meeks SL, Cox CL, Healey JF, Parker ET, Doshi BS, Gangadharan B, Barrow RT, Lollar P. A major determinant of the immunogenicity of factor VIII in a murine model is independent of its procoagulant function. Blood. 2012 Sep 20;120(12):2512-20. PubMed PMID: 22855607; PubMed Central PMCID: PMC3448263.
Meeks SL, Healey JF, Parker ET, Barrow RT, Lollar P. Non-classical anti-factor VIII C2 domain antibodies are pathogenic in a murine in vivo bleeding model. J Thromb Haemost. 2009 Apr;7(4):658-64. PubMed PMID: 19187078; PubMed Central PMCID: PMC2897237.
Meeks SL, Healey JF, Parker ET, Barrow RT, Lollar P. Nonclassical anti-C2 domain antibodies are present in patients with factor VIII inhibitors. Blood. 2008 Aug 15;112(4):1151-3. PubMed PMID: 18495957; PubMed Central PMCID: PMC2515124.
Meeks SL, Healey JF, Parker ET, Barrow RT, Lollar P. Antihuman factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation. Blood. 2007 Dec 15;110(13):4234-42. PubMed PMID: 17848617; PubMed Central PMCID: PMC2234776.
NHLBI-R01 – 4/1/2018-3/31/2023
Defining Initiating Factors Responsible for the Development of FVIII Inhibitors
Goals: To investigate the interactions that occur early on in the immune response between different immune components and to develop an assay to identify fVIII specific B cells in order to investigate the association between naïve precursor frequency and development of an immune response.
NHLBI-U54 – 3/1/2018-2/28/2023
Unraveling the Immune Response to Factor VIII
Goals: Leader of the administrative core and co-leader of the training core. Co-Investigator on all 3 projects. Two of these projects involve structural and functional analysis of different fVIII molecules and investigating immunogenicity and antigenicity of fVIII molecules. The third project focuses on the role of glycans in the immunogenicity of fVIII.
Role: Co-I