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
Travel Award to 5th International Congress of Immunology, Kyoto, Japan, from the American Association of Immunologists, 1983
M.S. (Honorary) University of Pennsylvania, 1991-1991

Memberships and Professional Organizations

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

Web Links


Selected Publications

Properdin-Mediated C5a Production Enhances Stable Binding of Platelets to Granulocytes in Human Whole Blood.

Blatt Adam Z, Saggu Gurpanna, Kulkarni Koustubh V, Cortes Claudio, Thurman Joshua M, Ricklin Daniel, Lambris John D, Valenzuela Jesus G, Ferreira Viviana P, Journal of immunology (Baltimore, Md. : 1950) 196(11): 4671-80, 2016, PMID:27183616

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Control of the collective migration of enteric neural crest cells by the Complement anaphylatoxin C3a and N-cadherin.

Broders-Bondon Florence, Paul-Gilloteaux Perrine, Gazquez Elodie, Heysch Julie, Piel Matthieu, Mayor Roberto, Lambris John D, Dufour Sylvie, Developmental biology 414(1): 85-99, 2016, PMID:27041467

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Complement in disease: a defence system turning offensive.

Ricklin Daniel, Reis Edimara S, Lambris John D, Nature reviews. Nephrology, 2016, PMID:27211870

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Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.

Forneris Federico, Wu Jin, Xue Xiaoguang, Ricklin Daniel, Lin Zhuoer, Sfyroera Georgia, Tzekou Apostolia, Volokhina Elena, Granneman Joke Cm, Hauhart Richard, Bertram Paula, Liszewski M Kathryn, Atkinson John P, Lambris John D, Gros Piet, The EMBO journal 35(10): 1133-49, 2016, PMID:27013439

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Differential capacity for complement receptor-mediated immune evasion by Porphyromonas gingivalis depending on the type of innate leukocyte.

Hajishengallis George, Krauss Jennifer L, Jotwani Ravi, Lambris John D, Molecular oral microbiology, 2016, PMID:27081768

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Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients.

Schmidt Christoph Q, Harder Markus J, Nichols Eva-Maria, Hebecker Mario, Anliker Markus, Höchsmann Britta, Simmet Thomas, Csincsi Ádám I, Uzonyi Barbara, Pappworth Isabel Y, Ricklin Daniel, Lambris John D, Schrezenmeier Hubert, Józsi Mihály, Marchbank Kevin J, Immunobiology 221(4): 503-11, 2016, PMID:26792457

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Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application.

Hajishengallis George, Hajishengallis Evlambia, Kajikawa Tetsuhiro, Wang Baomei, Yancopoulou Despina, Ricklin Daniel, Lambris John D, Seminars in immunology, 2016, PMID:27021500

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Combined Inhibition of Complement and CD14 Attenuates Bacteria-Induced Inflammation in Human Whole Blood More Efficiently Than Antagonizing the Toll-like Receptor 4-MD2 Complex.

Gustavsen Alice, Nymo Stig, Landsem Anne, Christiansen Dorte, Ryan Liv, Husebye Harald, Lau Corinna, Pischke Søren E, Lambris John D, Espevik Terje, Mollnes Tom E, The Journal of infectious diseases, 2016, PMID:26977050

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Comparative Analysis of Novel Complement-Targeted Inhibitors, MiniFH, and the Natural Regulators Factor H and Factor H-like Protein 1 Reveal Functional Determinants of Complement Regulation.

Harder Markus J, Anliker Markus, Höchsmann Britta, Simmet Thomas, Huber-Lang Markus, Schrezenmeier Hubert, Ricklin Daniel, Lambris John D, Barlow Paul N, Schmidt Christoph Q, Journal of immunology (Baltimore, Md. : 1950) 196(2): 866-76, 2016, PMID:26643478

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Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.

Maekawa Tomoki, Briones Ruel A, Resuello Ranillo R G, Tuplano Joel V, Hajishengallis Evlambia, Kajikawa Tetsuhiro, Koutsogiannaki Sophia, Garcia Cristina A G, Ricklin Daniel, Lambris John D, Hajishengallis George, Journal of clinical periodontology, 2016, PMID:26728318

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