PEOPLE

John D. Lambris, PhD

Dr. Ralph and Sallie Weaver Professor of Research Medicine
University of Pennsylvania Perelman School of Medicine

Contact Information401 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5765
Fax: (215) 573-8738

Email: LAMBRIS@UPENN.EDU

Specialty Division

Immunobiology and Experimental Pathology

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

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.

Education

B.S. (Biology), University of Patras, Greece, 1976
Ph.D. (Biochemistry), University of Patras, Greece, 1979

Specialty Certification

Postgraduate Training

Awards and Honors

Scholarship from the State Scholarship Institute for progress as a student in the Department of Biology, 1973-1976
Award from the Lawyer's Association of Patras as having ranked first among the three-year students of the Biological Department, 1974-1975
Fellowship from the National Research Foundation, Athens, Greece, 1977-1978
Long-term Fellowship from European Molecular Biology Organization ALTF 121-1982, 1982-1983
Fellowship from Alexander von Humboldt Foundation. This fellowship was declined in favor of the EMBO long-term fellowship, 1982-1983
M.S. (Honorary) University of Pennsylvania, 1991-1991
Honorary Doctorate, Linnaeus University, Kalmar, Sweden, 2006
Hans Kupczyk Guest Professor, University of Ulm, Ulm, Germany, 2012
Honorary Doctorate, Uppsala University, Uppsala, Sweden, 2013
Academy of Athens, Class of Sciences Awards, Athens, Greece, 2015

Memberships and Professional Organizations

National Science Foundation, Greece, - Present
Panepirotic Federation of America, Canada, & Australia, - Present
International Society of Developmental & Comparative Immunology, - Present
American Association for Advancement of Science, - Present
American Society for Biochemistry and Molecular Biology, - Present
Protein Society, - Present
American Association of Microbiologists, - Present
American Association of Immunologists, - Present
Biochemical Society (UK), - Present

Web Links


Selected Publications

Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair.

Kovtun Anna, Bergdolt Stephanie, Hägele Yvonne, Matthes Rebekka, Lambris John D, Huber-Lang Markus, Ignatius Anita, Scientific reports 7(1): 14061, 2017, PMID:29070810

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Complement-activation fragment C4a mediates effector functions by binding as untethered agonist to protease-activated receptors 1 and 4.

Wang HongBin, Ricklin Daniel, Lambris John D, Proceedings of the National Academy of Sciences of the United States of America 114(41): 10948-10953, 2017, PMID:28973891

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Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation.

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, Scandinavian journal of immunology 86(3): 143-155, 2017, PMID:28671713

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Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates.

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, Molecular therapy. Methods & clinical development 6(): 207-215, 2017, PMID:28879212

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Complement in cancer: untangling an intricate relationship.

Reis Edimara S, Mastellos Dimitrios C, Ricklin Daniel, Mantovani Alberto, Lambris John D, Nature Reviews. Immunology, 2017, PMID:28920587

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Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.

Xue Xiaoguang, Wu Jin, Ricklin Daniel, Forneris Federico, Di Crescenzio Patrizia, Schmidt Christoph Q, Granneman Joke, Sharp Thomas H, Lambris John D, Gros Piet, Nature structural & molecular biology 24(8): 643-651, 2017, PMID:28671664

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Complement component C3aR constitutes a novel regulator for chick eye morphogenesis.

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, Developmental biology 428(1): 88-100, 2017, PMID:28576690

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Alginate microbeads are coagulation compatible, while alginate microcapsules activate coagulation secondary to complement or directly through FXII.

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, Acta biomaterialia 58(): 158-167, 2017, PMID:28576714

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Porphyromonas gingivalis disturbs host-commensal homeostasis by changing complement function.

Olsen Ingar, Lambris John D, Hajishengallis George, Journal of oral microbiology 9(1): 1340085, 2017, PMID:28748042

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Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects.

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, Journal of Immunology 198(12): 4846-4854, 2017, PMID:28490576

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