John D. Lambris

faculty photo
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
Education:
B.S. (Biology)
University of Patras, Greece, 1976.
Ph.D. (Biochemistry)
University of Patras, Greece, 1979.
Permanent link
 

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

Description of Itmat Expertise

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.

Selected Publications

Reis ES, Berger N, Wang X, Koutsogiannaki S, Doot RK, Gumas JT, Foukas PG, Resuello RRG, Tuplano JV, Kukis D, Tarantal AF, Young AJ, Kajikawa T, Soulika A, Mastellos DC, Yancopoulou D, Biglarnia AR, Huber-Lang M, Hajishengallis G, Nilsson B, Lambris JD: Safety profile after prolonged C3 inhibition. Clin Immunol Sept 2018.

Bostanci Nagihan, Bao Kai, Li Xiaofei, Maekawa Tomoki, Grossmann Jonas, Panse Christian, Briones Ruel A, Resuello Ranillo R G, Tuplano Joel V, Garcia Cristina A G, Reis Edimara S, Lambris John D, Hajishengallis George: Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis. Journal of proteome research 17(9): 3153-3175, Sep 2018.

Reis Edimara S, Berger Nadja, Wang Xin, Koutsogiannaki Sophia, Doot Robert K, Gumas Justin T, Foukas Periklis G, Resuello Ranillo R G, Tuplano Joel V, Kukis David, Tarantal Alice F, Young Anthony J, Kajikawa Tetsushiro, Soulika Athena, Mastellos Dimitrios C, Yancopoulou Despina, Biglarnia Ali-Reza, Huber-Lang Markus, Hajishengallis George, Nilsson Bo, Lambris John D: Safety profile after prolonged C3 inhibition. Clinical Immunology Sep 2018.

Khandelwal Sanjay, Johnson Alexandra M, Liu Jian, Keire David, Sommers Cynthia, Ravi Joann, Lee Grace M, Lambris John D, Reis Edimara S, Arepally Gowthami M: Novel Immunoassay for Complement Activation by PF4/Heparin Complexes. Thrombosis and Haemostasis 118(8): 1484-1487, Aug 2018.

Mastellos DC, Reis ES, Yancopoulou D, Risitano AM, Lambris JD: Expanding Complement Therapeutics of the Treatment of Proxysmal Nocturnal Hemoglobinuris. Seminars in Hematology 55(3): 167, July 2018.

Mastellos Dimitrios C, Reis Edimara S, Yancopoulou Despina, Risitano Antonio M, Lambris John D: Expanding Complement Therapeutics for the Treatment of Paroxysmal Nocturnal Hemoglobinuria. Seminars in Hematology 55(3): 167-175, Jul 2018.

Sauter Reinhard J, Sauter Manuela, Reis Edimara S, Emschermann Frederic N, Nording Henry, Ebenhöch Sonja, Kraft Peter, Münzer Patrick, Mauler Maximilian, Rheinlaender Johannes, Madlung Johannes, Edlich Frank, Schäffer Tilman E, Meuth Sven G, Düerschmied Daniel, Geisler Tobias, Borst Oliver, Gawaz Meinrad, Kleinschnitz Christoph, Lambris John D, Langer Harald F: A Functional Relevance of the Anaphylatoxin Receptor C3aR for Platelet Function and Arterial Thrombus Formation Marks an Intersection Point Between Innate Immunity and Thrombosis. Circulation May 2018.

Huber-Lang Markus, Lambris John D, Ward Peter A: Innate immune responses to trauma. Nature Immunology 19(4): 327-341, Apr 2018.

Huber-Lang M, Lambris JD, Ward PA: Innate immune responses to trauma. Nature Immunology Mar 2018.

Mukai R, Okunuki Y, Husain D, Kim CB, Lambris JD, Connor KM: The Complement System Is Critical in Maintaining Retinal Integrity during Aging. Frontiers in Aging Neuroscience 10(15), Feb 2018.

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Last updated: 09/23/2018
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