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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

Georgoutsou-Spyridonos Maria, Ricklin Daniel, Pratsinis Haris, Perivolioti Eustathia, Pirmettis Ioannis, Garcia Brandon L, Geisbrecht Brian V, Foukas Periklis G, Lambris John D, Mastellos Dimitrios C, Sfyroera Georgia: Attenuation of Staphylococcus aureus-Induced Bacteremia by Human Mini-Antibodies Targeting the Complement Inhibitory Protein Efb. Journal of immunology (Baltimore, Md. : 1950) Sep 2015.

Zipfel Peter F, Skerka Christine, Chen Qian, Wiech Thorsten, Goodship Tim, Johnson Sally, Fremeaux-Bacchi Veronique, Nester Clara, de Córdoba Santiago Rodríguez, Noris Marina, Pickering Matthew, Smith Richard: The role of complement in C3 glomerulopathy. Molecular immunology 67(1): 21-30, Sep 2015.

Silasi-Mansat Robert, Zhu Hua, Georgescu Constantin, Popescu Narcis, Keshari Ravi S, Peer Glenn, Lupu Cristina, Taylor Fletcher B, Pereira Heloise Anne, Kinasewitz Gary, Lambris John D, Lupu Florea: Complement inhibition decreases early fibrogenic events in the lung of septic baboons. Journal of cellular and molecular medicine Sep 2015.

Reis Edimara S, Mastellos Dimitrios C, Yancopoulou Despina, Risitano Antonio M, Ricklin Daniel, Lambris John D: Applying complement therapeutics to rare diseases. Clinical immunology (Orlando, Fla.) Sep 2015.

Mastellos Dimitrios C, Ricklin Daniel, Hajishengallis Evlambia, Hajishengallis George, Lambris John D: Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention. Molecular oral microbiology Aug 2015.

Zhang Yuzhou, Shao Dingwu, Ricklin Daniel, Hilkin Brieanna M, Nester Carla M, Lambris John D, Smith Richard J H: Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3 glomerulopathy. Immunobiology 220(8): 993-8, Aug 2015.

Lin Zhuoer, Schmidt Christoph Q, Koutsogiannaki Sophia, Ricci Patrizia, Risitano Antonio M, Lambris John D, Ricklin Daniel: Complement C3dg-mediated erythrophagocytosis: implications for paroxysmal nocturnal hemoglobinuria. Blood 126(7): 891-4, Aug 2015.

Hamad O A, Mitroulis I, Fromell K, Kozarcanin H, Chavakis T, Ricklin D, Lambris J D, Ekdahl K N, Nilsson B: Contact activation of C3 enables tethering between activated platelets and polymorphonuclear leukocytes via CD11b/CD18. Thrombosis and haemostasis 114(5), Aug 2015.

Sweigard J Harry, Matsumoto Hidetaka, Smith Kaylee E, Kim Leo A, Paschalis Eleftherios I, Okonuki Yoko, Castillejos Alexandra, Kataoka Keiko, Hasegawa Eiichi, Yanai Ryoji, Husain Deeba, Lambris John D, Vavvas Demetrios, Miller Joan W, Connor Kip M: Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury. Science translational medicine 7(297): 297ra116, Jul 2015.

Ricklin Daniel, Lambris John D: Therapeutic control of complement activation at the level of the central component C3. Immunobiology Jun 2015.

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Last updated: 09/15/2015
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