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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

Blatt Adam Z, Saggu Gurpanna, Kulkarni Koustubh V, Cortes Claudio, Thurman Joshua M, Ricklin Daniel, Lambris John D, Valenzuela Jesus G, Ferreira Viviana P: Properdin-Mediated C5a Production Enhances Stable Binding of Platelets to Granulocytes in Human Whole Blood. Journal of immunology (Baltimore, Md. : 1950) 196(11): 4671-80, Jun 2016.

Broders-Bondon Florence, Paul-Gilloteaux Perrine, Gazquez Elodie, Heysch Julie, Piel Matthieu, Mayor Roberto, Lambris John D, Dufour Sylvie: Control of the collective migration of enteric neural crest cells by the Complement anaphylatoxin C3a and N-cadherin. Developmental biology 414(1): 85-99, Jun 2016.

Ricklin Daniel, Reis Edimara S, Lambris John D: Complement in disease: a defence system turning offensive. Nature reviews. Nephrology May 2016.

Forneris Federico, Wu Jin, Xue Xiaoguang, Ricklin Daniel, Lin Zhuoer, Sfyroera Georgia, Tzekou Apostolia, Volokhina Elena, Granneman Joke Cm, Hauhart Richard, Bertram Paula, Liszewski M Kathryn, Atkinson John P, Lambris John D, Gros Piet: Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode. The EMBO journal 35(10): 1133-49, May 2016.

Hajishengallis George, Krauss Jennifer L, Jotwani Ravi, Lambris John D: Differential capacity for complement receptor-mediated immune evasion by Porphyromonas gingivalis depending on the type of innate leukocyte. Molecular oral microbiology Apr 2016.

Schmidt Christoph Q, Harder Markus J, Nichols Eva-Maria, Hebecker Mario, Anliker Markus, Höchsmann Britta, Simmet Thomas, Csincsi Ádám I, Uzonyi Barbara, Pappworth Isabel Y, Ricklin Daniel, Lambris John D, Schrezenmeier Hubert, Józsi Mihály, Marchbank Kevin J: Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients. Immunobiology 221(4): 503-11, Apr 2016.

Hajishengallis George, Hajishengallis Evlambia, Kajikawa Tetsuhiro, Wang Baomei, Yancopoulou Despina, Ricklin Daniel, Lambris John D: Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application. Seminars in immunology Mar 2016.

Gustavsen Alice, Nymo Stig, Landsem Anne, Christiansen Dorte, Ryan Liv, Husebye Harald, Lau Corinna, Pischke Søren E, Lambris John D, Espevik Terje, Mollnes Tom E: Combined Inhibition of Complement and CD14 Attenuates Bacteria-Induced Inflammation in Human Whole Blood More Efficiently Than Antagonizing the Toll-like Receptor 4-MD2 Complex. The Journal of infectious diseases Mar 2016.

Harder Markus J, Anliker Markus, Höchsmann Britta, Simmet Thomas, Huber-Lang Markus, Schrezenmeier Hubert, Ricklin Daniel, Lambris John D, Barlow Paul N, Schmidt Christoph Q: 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 (Baltimore, Md. : 1950) 196(2): 866-76, Jan 2016.

Maekawa Tomoki, Briones Ruel A, Resuello Ranillo R G, Tuplano Joel V, Hajishengallis Evlambia, Kajikawa Tetsuhiro, Koutsogiannaki Sophia, Garcia Cristina A G, Ricklin Daniel, Lambris John D, Hajishengallis George: Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3. Journal of clinical periodontology Jan 2016.

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Last updated: 09/15/2015
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