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John D. Lambris, Ph.D.

Dr. Ralph and Sallie Weaver Professor of Research Medicine
Department: Pathology and Laboratory Medicine

Contact information
401 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5765
Fax: (215) 573-8738
B.S. (Biology)
University of Patras, Greece, 1976.
Ph.D. (Biochemistry)
University of Patras, Greece, 1979.
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Description of Research Expertise

Research Interests

Complement, Inflammation, Cancer, Systems Biology, Therapeutics, Peptides, Innate Immunity, liver regeneration, sepsis

Research Summary

Using complement as a model system we apply ideas and methods embodied in engineering, computer science, physics, chemistry, and other fields to address today’s challenges in biomedical research.

The complement system has been long appreciated as a major effector arm of the innate immune response. It consists of a complex group of serum proteins and glycoproteins and soluble or membrane-bound receptors, which play an important role in host defense against infection. Complement, a phylogenetically conserved arm of innate immunity, functions together with the adaptive immune response by serving as an important inflammatory mediator of antigen-antibody interactions. It also provides an interface between the innate and adaptive immune response by contributing to the enhancement of the humoral response mounted against specific antigens. 

In an era that nurtures the integrated study of biological systems as the prevalent concept in contemporary scientific thinking, complement research is being revisited and our current knowledge of this innate immune system is enriched by findings that point to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation.

Departing from traditional hallmarks of molecular biology such as the genome and the transcriptome and beginning to appreciate more the “proteome” as the dynamic expression profile and unique ‘fingerprint’ of all organisms, novel associations between biochemical pathways and apparently unrelated biological processes are constantly revealed. In this respect, recent evidence produced by our laboratory (and others) suggests that complement components can modulate diverse biological processes by closely interacting with other intra- and intercellular networks.

Furthermore, the structure and functions of several complement proteins as well as the protein-protein interactions that underlie these functions are now being investigated with the aid of cross-disciplinary approaches ranging from mathematics and biophysics to comparative phylogenesis, in silico studies, mimetics and proteomics. Our laboratory, extending its research beyond the scope of traditional complement pathobiology, has embraced this global and combinatorial approach to biomedical research and has been actively engaged in defining the function of complement proteins in several biological contexts and pathophysiological states.

Our current research efforts focus on the structural-functional aspects of protein-protein interactions and the rational design of small-size complement inhibitors. We also study the viral molecular mimicry and immune evasion strategies, as well as the evolution of complement biology. In addition we study the involvement of various complement components with developmental pathways and the role of complement in tissue regeneration, early hematopoietic development and cancer.

For updated information please visit WWW.LAMBRIS.NET

Selected Publications

Bonavita Eduardo, Gentile Stefania, Rubino Marcello, Maina Virginia, Papait Roberto, Kunderfranco Paolo, Greco Carolina, Feruglio Francesca, Molgora Martina, Laface Ilaria, Tartari Silvia, Doni Andrea, Pasqualini Fabio, Barbati Elisa, Basso Gianluca, Galdiero Maria Rosaria, Nebuloni Manuela, Roncalli Massimo, Colombo Piergiuseppe, Laghi Luigi, Lambris John D, Jaillon Sébastien, Garlanda Cecilia, Mantovani Alberto: PTX3 Is an Extrinsic Oncosuppressor Regulating Complement-Dependent Inflammation in Cancer. Cell 160(4): 700-14, Feb 2015.

Sfyroera G, Ricklin D, Reis ES, Chen H, Wu EL, Kaznessis YN, Ekdahl KN, Nilsson B, Lambris JD: Rare Loss-of-Function Mutation in Complement Component C3 Provides Insight into Molecular and Pathophysiological Determinants of Complement Activity. Journal of Immunology Feb. 2015.

Rafail Stavros, Kourtzelis Ioannis, Foukas Periklis G, Markiewski Maciej M, DeAngelis Robert A, Guariento Mara, Ricklin Daniel, Grice Elizabeth A, Lambris John D: Complement deficiency promotes cutaneous wound healing in mice. Journal of immunology (Baltimore, Md. : 1950) 194(3): 1285-91, Feb 2015.

Mastellos Dimitrios C, Yancopoulou Despina, Kokkinos Petros, Huber-Lang Markus, Hajishengallis George, Biglarnia Ali Reza, Lupu Florea, Nilsson Bo, Risitano Antonio M, Ricklin Daniel, Lambris John D: Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention. European journal of clinical investigation Feb 2015.

Kourtzelis I, Ferreira A, Mitroulis I, Ricklin D, Bornstein S R, Waskow C, Lambris J D, Chavakis T: Complement inhibition in a xenogeneic model of interactions between human whole blood and porcine endothelium. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme 47(1): 36-42, Jan 2015.

Hajishengallis George, Chavakis Triantafyllos, Hajishengallis Evlambia, Lambris John D: Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. Journal of leukocyte biology Dec 2014.

Woehl Jordan L, Stapels Daphne A C, Garcia Brandon L, Ramyar Kasra X, Keightley Andrew, Ruyken Maartje, Syriga Maria, Sfyroera Georgia, Weber Alexander B, Zolkiewski Michal, Ricklin Daniel, Lambris John D, Rooijakkers Suzan H M, Geisbrecht Brian V: 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 193(12): 6161-71, Dec 2014.

Reis Edimara S, DeAngelis Robert A, Chen Hui, Resuello Ranillo R G, Ricklin Daniel, Lambris John D: Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters. Immunobiology Nov 2014.

Mastellos Dimitrios C, Ricklin Daniel, Yancopoulou Despina, Risitano Antonio, Lambris John D: Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape. Expert review of hematology 7(5): 583-98, Oct 2014.

Moll Guido, Alm Jessica J, Davies Lindsay C, von Bahr Lena, Heldring Nina, Stenbeck-Funke Lillemor, Hamad Osama A, Hinsch Robin, Ignatowicz Lech, Locke Matthew, Lönnies Helena, Lambris John D, Teramura Yuji, Nilsson-Ekdahl Kristina, Nilsson Bo, Le Blanc Katarina: Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem cells (Dayton, Ohio) 32(9): 2430-42, Sep 2014.

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Last updated: 03/10/2015
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