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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

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.

Song Delu, Grieco Steve, Li Yafeng, Hunter Allan, Chu Sally, Zhao Liangliang, Song Ying, DeAngelis Robert A, Shi Lan-Ying, Liu Qin, Pierce Eric A, Nishina Patsy M, Lambris John D, Dunaief Joshua L: A Murine Rp1 Missense Mutation Causes Protein Mislocalization and Slowly Progressive Photoreceptor Degeneration. The American journal of pathology Aug 2014.

Sweigard J Harry, Yanai Ryoji, Gaissert Philipp, Saint-Geniez Magali, Kataoka Keiko, Thanos Aristomenis, Stahl Gregory L, Lambris John D, Connor Kip M: The alternative complement pathway regulates pathological angiogenesis in the retina. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28(7): 3171-82, Jul 2014.

Huang Yijun, Reis Edimara S, Knerr Patrick J, van der Donk Wilfred A, Ricklin Daniel, Lambris John D: Conjugation to Albumin-Binding Molecule Tags as a Strategy to Improve Both Efficacy and Pharmacokinetic Properties of the Complement Inhibitor Compstatin. ChemMedChem Jul 2014.

Maekawa Tomoki, Abe Toshiharu, Hajishengallis Evlambia, Hosur Kavita B, DeAngelis Robert A, Ricklin Daniel, Lambris John D, Hajishengallis George: Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. Journal of immunology (Baltimore, Md. : 1950) 192(12): 6020-7, Jun 2014.

Maekawa Tomoki, Krauss Jennifer L, Abe Toshiharu, Jotwani Ravi, Triantafilou Martha, Triantafilou Kathy, Hashim Ahmed, Hoch Shifra, Curtis Michael A, Nussbaum Gabriel, Lambris John D, Hajishengallis George: Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell host & microbe 15(6): 768-78, Jun 2014.

Lupu Florea, Keshari Ravi S, Lambris John D, Mark Coggeshall K: Crosstalk between the coagulation and complement systems in sepsis. Thrombosis research 133 Suppl 1: S28-31, May 2014.

Klapper Yvonne, Hamad Osama A, Teramura Yuji, Leneweit Gero, Nienhaus G Ulrich, Ricklin Daniel, Lambris John D, Ekdahl Kristina N, Nilsson Bo: Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles. Biomaterials 35(11): 3688-96, Apr 2014.

Clarkson Benjamin D S, Ling Changying, Shi Yejie, Harris Melissa G, Rayasam Aditya, Sun Dandan, Salamat M Shahriar, Kuchroo Vijay, Lambris John D, Sandor Matyas, Fabry Zsuzsanna: T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice. The Journal of experimental medicine 211(4): 595-604, Apr 2014.

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Last updated: 09/18/2014
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