John D. Lambris, Ph.D.

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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

Kovtun Anna, Bergdolt Stephanie, Hägele Yvonne, Matthes Rebekka, Lambris John D, Huber-Lang Markus, Ignatius Anita: Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair. Scientific reports 7(1): 14061, Oct 2017.

Wang HongBin, Ricklin Daniel, Lambris John D: Complement-activation fragment C4a mediates effector functions by binding as untethered agonist to protease-activated receptors 1 and 4. Proceedings of the National Academy of Sciences of the United States of America 114(41): 10948-10953, Oct 2017.

Denk S, Taylor R P, Wiegner R, Cook E M, Lindorfer M A, Pfeiffer K, Paschke S, Eiseler T, Weiss M, Barth E, Lambris J D, Kalbitz M, Martin T, Barth H, Messerer D A C, Gebhard F, Huber-Lang M S: Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation. Scandinavian journal of immunology 86(3): 143-155, Sep 2017.

Kajikawa Tetsuhiro, Briones Ruel A, Resuello Ranillo R G, Tuplano Joel V, Reis Edimara S, Hajishengallis Evlambia, Garcia Cristina A G, Yancopoulou Despina, Lambris John D, Hajishengallis George: Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates. Molecular therapy. Methods & clinical development 6: 207-215, Sep 2017.

Reis Edimara S, Mastellos Dimitrios C, Ricklin Daniel, Mantovani Alberto, Lambris John D: Complement in cancer: untangling an intricate relationship. Nature Reviews. Immunology Sep 2017.

Xue Xiaoguang, Wu Jin, Ricklin Daniel, Forneris Federico, Di Crescenzio Patrizia, Schmidt Christoph Q, Granneman Joke, Sharp Thomas H, Lambris John D, Gros Piet: Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses. Nature structural & molecular biology 24(8): 643-651, Aug 2017.

Grajales-Esquivel Erika, Luz-Madrigal Agustin, Bierly Jeffrey, Haynes Tracy, Reis Edimara S, Han Zeyu, Gutierrez Christian, McKinney Zachary, Tzekou Apostolia, Lambris John D, Tsonis Panagiotis A, Del Rio-Tsonis Katia: Complement component C3aR constitutes a novel regulator for chick eye morphogenesis. Developmental biology 428(1): 88-100, Aug 2017.

Gravastrand Caroline, Hamad Shamal, Fure Hilde, Steinkjer Bjørg, Ryan Liv, Oberholzer Josè, Lambris John D, Lacík Igor, Mollnes Tom Eirik, Espevik Terje, Brekke Ole-Lars, Rokstad Anne Mari: Alginate microbeads are coagulation compatible, while alginate microcapsules activate coagulation secondary to complement or directly through FXII. Acta biomaterialia 58: 158-167, Aug 2017.

Olsen Ingar, Lambris John D, Hajishengallis George: Porphyromonas gingivalis disturbs host-commensal homeostasis by changing complement function. Journal of oral microbiology 9(1): 1340085, Jun 2017.

Denk Stephanie, Neher Miriam D, Messerer David A C, Wiegner Rebecca, Nilsson Bo, Rittirsch Daniel, Nilsson-Ekdahl Kristina, Weckbach Sebastian, Ignatius Anita, Kalbitz Miriam, Gebhard Florian, Weiss Manfred E, Vogt Josef, Radermacher Peter, Köhl Jörg, Lambris John D, Huber-Lang Markus S: Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects. Journal of Immunology 198(12): 4846-4854, Jun 2017.

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Last updated: 11/27/2017
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