M. Kathryn Liszewski, PhD

Research interests

My research focuses on regulation of the Complement System. Discovered more than 100 years ago, this system consists of three powerful pathways with more than 30 proteins that provide both a rapid (within microseconds) and powerful response to infection. Overactivation or dysfunction in its regulation results in a wide spectrum of diseases including systemic lupus erythematosus (SLE), hemolytic uremic syndrome (HUS), rheumatoid arthritis and many others. One of the major complement regulators on most cells of the body is membrane cofactor protein (MCP; CD46). With a system as powerful as complement, host cells must be protected from accidental damage. MCP helps protect host cells by serving as a cofactor for serine protease factor I that proteolytically inactivates two main components, C3 and C4. Mutations in this protein have been associated not only with atypical HUS, but also the pregnancy-related disorder pre-eclampsia. I am studying the structure and function of MCP. Creating cellular models by mutating and then expressing MCP allows provides a better understand of its function and anomalies.

Publications

  1. Salmon JE, Heuser C, Triebwasser M, Liszewski MK, et al., Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort. PLOS Med 2011: 8: e1001013
  2. Van der Werf CS, Sribudiani Y, Verheij JB, Carroll M, O’Loughlin E, Chen CH, Brooks AS, Liszewski MK, Atkinson JP, Hofstra RM, Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations, Genet Med 2013: 15: 310-313
  3. Mohlin FC, Mercier E, Fremeaux-Bacchi V, Liszewski MK, Atkinson JP, Gris JC, Blom AM, Analysis of genes coding for CD46, CD55 and C4b-binding protein in patients with idiopathic, recurrent, spontaneous pregnancy loss. European J Immunol 2013: 43: 1617-1629
  4. Liszewski MK, Kolev M, Le Friec G, Leung M, Bertram PG, Fara A, Subias M, Pickering MC, Drouet C, Meri S, Arstila TP, Pekkarinen PT, Ma M, Cope A, Reinheckel T, Rodriguez de Cordoba S, Afzali B, Atkinson JP, and Kemper C. Intracellular Complement Activation Sustains T Cell Homeostasis and Mediates Effector Differentiation. Immunity 2013: 39: 1143-1157
  5. Park HJ,  Guariento, M, Maciejewski  M, Hauhart R, Tham W-H, Cowman AF, Schmidt CQ, Mertens H, Liszewski MK, Hourcade D, Barlow P and Atkinson JP.  Using mutagenesis and structural biology to map the binding site for Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor. J. Biol Chem, 2014: 289: 450-463
  6. Java A, Liszewski, MK, Hourcade, DH, and Atkinson, JP. The rold of complement receptor one (CR1; CD35) on epithelial cells. A model for understanding complement-mediated disease in the kidney. Mol. Imm. 2015: 67: 584-595.
  7. Liszewski MK, Atkinson JP, Complement Regulators in Human Disease: Lessons from Modern Genetics. Journal of Internal Medicine 2015: 277:  294-305
  8. Liszewski MK, Atkinson JP. Complement Regulator CD46: Genetic Variants and Disease Associations. Human Genomics 2015: 9: 7-20
  9. Schramm, EC, Java, AJ, Liszewski, MK and Atkinson JP, Complement deficiencies associated with atypical hemolytic uremic syndrome. Encyclopedia of Medical Immunology, in press 2015