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Daniel Ricklin, Ph.D.

Daniel Ricklin, Ph.D.

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Research Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine

Contact information
401 Stellar Chance
422 Curie Blvd.
Philadelphia, PA 19104
Office: 215-746-5760
Fax: 215-573-8738
Lab: 215-746-5767
Education:
M.Sc. (Pharmaceutical Sciences)
Swiss Federal Institute of Technology (ETH), Zurich, Switzerland, 1999.
Ph.D. (Pharmaceutical Chemistry, Biophysics)
University of Basel, Switzerland, 2005.
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Description of Research Expertise

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.

Selected Publications

Ricklin D, Hajishengallis G, Yang K, Lambris JD: Complement: a key system for immune surveillance and homeostasis. Nature Immunol 11(9): 785-97, Aug 2010.

Ricklin D, Lambris JD: Complement in immune and inflammatory disorders: therapeutic interventions. Journal of Immunology 190(8): 3839-47, Apr 2013.

Ricklin D, Lambris JD: Complement in immune and inflammatory disorders: pathophysiological mechanisms. Journal of Immunology 190(8): 3831-8, Apr 2013.

Qu H*, Ricklin D*, Bai H, Chen H, Reis ES, Maciejewski M, Tzekou A, DeAngelis RA, Resuello RRG, Lupu F, Barlow PN, Lambris JD: New analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties. Immunobiology 218(4): 496-505, Apr 2013 Notes: *equal contribution.

Oikonomopoulou K, Deangelis RA, Chen H, Diamandis EP, Hollenberg MD, Ricklin D*, Lambris JD*: Induction of Complement C3a Receptor Responses by Kallikrein-Related Peptidase 14. Journal of Immunology 191(7): 3858-66, Oct 2013 Notes: *shared supervision.

Schmidt CQ, Bai H, Lin Z, Risitano AM, Barlow PN, Ricklin D*, Lambris JD*: Rational engineering of a novel complement regulator affords double targeting of host cells and controls innate immunity in disease condition. Journal of Immunology 190(11): 5712-21, June 2013 Notes: * shared supervision.

Reis ES, Chen H, Sfyroera G, Monk PN, Köhl J, Lambris JD*, Ricklin D*: C5a Receptor-Dependent Cell Activation by Physiological Concentrations of Desarginated C5a: Insights from a Novel Label-Free Cellular Assay. Journal of Immunology 189(10): 4797-805, Nov 2012 Notes: *shared supervision.

Wu YQ, Qu H, Sfyroera G, Tzekou A, Kay BK, Nilsson B, Nilsson Ekdahl K, Ricklin D*, Lambris JD*: Protection of nonself surfaces from complement attack by factor H-binding peptides: implications for therapeutic medicine. Journal of Immunology 186(7): 4269-77, April 2011 Notes: *shared supervision.

Chen H*, Ricklin D*, Hammel M, Garcia BL, McWhorter WJ, Sfyroera G, Wu YQ, Tzekou A, Li S, Geisbrecht BV, Woods VL Jr, Lambris JD.: 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(41): 17621-6, Oct 2010 Notes: *equal contribution.

Forneris F, Ricklin D, Wu J, Tzekou A, Wallace RS, Lambris JD, Gros P: Structures of C3b in Complex with Factors B and D Give Insight into Complement Convertase Formation. Science 330(6012): 1816-20, Dec 2010.

Ricklin D, Tzekou A, Garcia BL, Hammel M, McWhorter WJ, Sfyroera G, Wu YQ, Holers VM, Herbert AP, Barlow PN, Geisbrecht BV, Lambris JD: A molecular insight into complement evasion by the staphylococcal complement inhibitor protein family. Journal of Immunology 183(4): 2565-74, Aug 2009.

Wu J, Wu YQ, Ricklin D, Janssen BJC, Lambris JD, Gros P: Structure of complement fragment C3b-factor H and implications for host protection by complement regulators. Nature Immunology 10(7): 728-33, Jul 2009.

Rooijakkers SHM, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, Ricklin D, Lambris JD, Janssen BJC, van Strijp JAG, Gros P: Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor. Nature Immunology 10(7): 721-7, Jul 2009.

Petrou PS*, Ricklin D*, Zavali M, Raptis I, Kakabakos SE, Misiakos K, Lambris JD: Real-time label-free detection of complement activation products in human serum by white light reflectance spectroscopy. Biosensors & Bioelectronics 24(11): 3359-64, Jul 2009 Notes: *equal contribution.

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Last updated: 10/29/2014
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