Daniel Ricklin, Ph.D.
Current PositionResearch Assistant Professor
EducationPh.D, University of Basel, Molecular Pharmacy Group (2005)
M.Sc, Swiss Federal Institute of Technology (ETH), Pharmaceutical Sciences (1999)
The primary focus of my research efforts is on the molecular elucidation of the role of the human complement system in health and disease. In recent years, a body of research has impressively demonstrated that the function of the complement system reaches far beyond the detection and elimination of microbial intruders but covers a broad range from immune modulation and metabolism to cell development and homeostasis, which require a highly tailored and context-specific response. Using an integrated approach based on biophysical (e.g., surface plasmon resonance), biochemical, structural, and cell-based techniques, my goal is to shed light into the underlying processes of complement activation and regulation, as well as to describe its molecular connections to associated physiological pathways. At the same time, it has become evident that any disruption of the careful balance between activation and regulation may contribute to pathological processes, and a number of complement-related diseases have been described in recent years and put complement-directed drug discovery into the spotlight. At the same time, complement is also involved in adverse effects observed in connection with the emerging field of biomaterials in modern medicine (e.g., implants, drug delivery devices). One aspect of my research therefore focuses on the discovery and development of potent inhibitors that allow for a therapeutic modulation of the complement cascade at various stages, and on the evaluation of such inhibitors in clinically relevant models. Finally, I am investigating the fascinating immune evasion mechanisms that human pathogens developed through millennia of co-evolution with their host. Focusing on Staphylococcus aureus, I examine various bacterial inhibitors directed against complement and other immune pathways, and explore their implications on immune activity and their potential as templates for therapeutics.
Wu J, Wu YQ, Ricklin D, Janssen BJ, Gros P, Lambris JD. (2009). Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nature Immunology 10: 728-33. Additional Links: Supplementary Information.
Hammel M, Sfyroera G, Ricklin D, Magotti P, Lambris JD, Geisbrecht BV,. (2007). A structural basis for complement inhibition by Staphylococcus aureus. Nature Immunology
Garcia BL, Tzekou A, Ramyar KX, McWhorter WJ, Ricklin D, Lambris JD, Geisbrecht BV. (2009). Crystallization of human complement component C3b in the presence of a staphylococcal complement-inhibitor protein (SCIN). Acta crystallographica. Section F, Structural biology and crystallization communications 65: 482-5.
Chen H, Ricklin D, Hammel M, Garcia BL, McWhorter WJ, Sfyroera G, Wu YQ, Tzekou A, Li S, Geisbrecht BV, Woods VL, Lambris JD. (2010). Allosteric inhibition of complement function by a staphylococcal immune evasion protein. Proceedings of the National Academy of Sciences of the United States of America 107: 17621-6:. Additional Links: Supplementary Information.
Rooijakkers SH, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, Ricklin D, Lambris JD, Janssen BJ, van Strijp JA, Gros P. (2009). Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nature immunology 10: 721-7. Additional Links: Supplementary Information.
Wu YQ, Qu H, Sfyroera G, Tzekou A, Kay BK, Nilsson B, Nilsson Ekdahl K, Ricklin D*, Lambris JD*. (2011). Protection of nonself surfaces from complement attack by factor h-binding peptides: implications for therapeutic medicine. Journal of Immunology 186: 4269-77. * Shared Supervision
. Additional Links: erratum.
Garcia BL, Ramyar KX, Tzekou A, Ricklin D, McWhorter WJ, Lambris JD, Geisbrecht BV. (2010). Molecular basis for complement recognition and inhibition determined by crystallographic studies of the staphylococcal complement inhibitor (SCIN) bound to C3c and C3b. Journal of Molecular Biology 402: 17-29.
Forneris F, Ricklin D, Wu J, Tzekou A, Wallace RS, Lambris JD, Gros P. (2011). Structures of C3b in complex with factors B and D give insight into complement convertase formation. Science 330: 1816-20. Additional Links: Supplementary Information.
Qu H, Ricklin D, Bai H, Chen H, Reis ES, Maciejewski M, Tzekou A, Deangelis RA, Resuello RR, Lupu F, Barlow PN, Lambris JD. (2013). New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties. Immunobiology 218: 496-505. Additional Links: Supplement.
Reis ES, Chen H, Sfyroera G, Monk PN, Köhl J, Ricklin D, Lambris JD. (2012). C5a receptor-dependent cell activation by physiological concentrations of desarginated c5a: insights from a novel label-free cellular assay. Journal of Immunology 189: 4797-805. Additional Links: In this Issue.
Kourtzelis I, Rafail S, DeAngelis RA, Foukas PG, Ricklin D, Lambris JD,. (2013). Inhibition of biomaterial-induced complement activation attenuates the inflammatory host response to implantation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27: 2768-76.
Risitano AM, Ricklin D, Huang Y, Reis ES, Chen H, Ricci P, Lin Z, Pascariello C, Raia M, Sica M, Del Vecchio L, Pane F, Lupu F, Notaro R, Resuello RR, Deangelis RA, Lambris JD. (2014). Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. Blood 123: 2094-101. Additional Links: Inside Blood.
Woehl JL, Stapels DA, Garcia BL, Ramyar KX, Keightley A, Ruyken M, Syriga M, Sfyroera G, Weber AB, Zolkiewski M, Ricklin D, Lambris JD, Rooijakkers SH, Geisbrecht BV,. (2014). The Extracellular Adherence Protein from Staphylococcus aureus Inhibits the Classical and Lectin Pathways of Complement by Blocking Formation of the C3 Proconvertase. Journal of immunology (Baltimore, Md. : 1950) 193: 6161-71.
Georgoutsou-Spyridonos M, Ricklin D, Pratsinis H, Perivolioti E, Pirmettis I, Garcia BL, Geisbrecht BV, Foukas PG, Lambris JD, Mastellos DC, Sfyroera G. (2015). Attenuation of Staphylococcus aureus-Induced Bacteremia by Human Mini-Antibodies Targeting the Complement Inhibitory Protein Efb. Journal of Immunology 195: 3946-58. Additional Links: Top 10% of October 2015.
Harder MJ, Anliker M, Höchsmann B, Simmet T, Huber-Lang M, Schrezenmeier H, Ricklin D, Lambris JD, Barlow PN, Schmidt CQ. (2016). Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H-like Protein 1 Reveal Functional Determinants of Complement Regulation. Journal of Immunology 196: 866-76.
Maekawa T, Briones RA, Resuello RR, Tuplano JV, Hajishengallis E, Kajikawa T, Koutsogiannaki S, Garcia CA, Ricklin D, Lambris JD, Hajishengallis G. (2016). Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3. Journal of Clinical Periodontology :.
Schmidt CQ, Harder MJ, Nichols EM, Hebecker M, Anliker M, Höchsmann B, Simmet T, Csincsi Á, Uzonyi B, Pappworth IY, Ricklin D, Lambris JD, Schrezenmeier H, Józsi M, Marchbank KJ. (2016). Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients.. Immunobiology 221: 503-11.
Primikyri A, Papanastasiou M, Sarigiannis Y, Koutsogiannaki S, Reis ES, Tuplano JV, Resuello RR, Nilsson B, Ricklin D, Lambris JD. (2016). Method development and validation for the quantitation of the complement inhibitor Cp40 in human and cynomolgus monkey plasma by UPLC-ESI-MS. Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Sciences 1041-1042: 19-26.
Papanastasiou M, Koutsogiannaki S, Sarigiannis Y, Geisbrecht BV, Ricklin D, Lambris JD. (2017). Structural Implications for the Formation and Function of the Complement Effector Protein iC3b. Journal of immunology 198: 3326-3335. Additional Links: Cover JI.