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
Fellowship from Alexander von Humboldt Foundation. This fellowship was declined in favor of the EMBO long-term fellowship, 1982-1983
Long-term Fellowship from European Molecular Biology Organization ALTF 121-1982, 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

Structural Implications for the Formation and Function of the Complement Effector Protein iC3b

Malvina Papanastasiou, Sophia Koutsogiannaki, Yiannis Sarigiannis, Brian V. Geisbrecht, Daniel Ricklin and John D. Lambris, Journal of immunology (Baltimore, Md. : 1950), 2017, PMID:28258193

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Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation.

Harder Markus J, Kuhn Nadine, Schrezenmeier Hubert, Höchsmann Britta, von Zabern Inge, Weinstock Christof, Simmet Thomas, Ricklin Daniel, Lambris John D, Skerra Arne, Anliker Markus, Schmidt Christoph Q, Blood 129(8): 970-980, 2017, PMID:28028023

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Complement C3 inhibitor Cp40 attenuates xenoreactions in pig hearts perfused with human blood.

Abicht Jan-Michael, Kourtzelis Ioannis, Reichart Bruno, Koutsogiannaki Sophia, Primikyri Alexandra, Lambris John D, Chavakis Triantafyllos, Holdt Lesca, Kind Alexander, Guethoff Sonja, Mayr Tanja, Xenotransplantation 24(1): , 2017, PMID:27677785

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Method development and validation for the quantitation of the complement inhibitor Cp40 in human and cynomolgus monkey plasma by UPLC-ESI-MS.

Primikyri Alexandra, Papanastasiou Malvina, Sarigiannis Yiannis, Koutsogiannaki Sophia, Reis Edimara S, Tuplano Joel V, Resuello Ranillo R G, Nilsson Bo, Ricklin Daniel, Lambris John D, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 1041-1042(): 19-26, 2017, PMID:27992787

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Pericyte and immune cells contribute to complement activation in tubulointerstitial fibrosis.

Xavier Sandhya, Sahu Ranjit K, Landes Susan G, Yu Jing, Taylor Ronald P, Ayyadevara Srinivas, Megyesi Judit, Stallcup William B, Duffield Jeremy S, Reis Edimara S, Lambris John D, Portilla Didier, American journal of physiology. Renal physiology, 2017, PMID:28052876

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More than complementing Tolls: complement-Toll-like receptor synergy and crosstalk in innate immunity and inflammation.

Hajishengallis George, Lambris John D, Immunological reviews 274(1): 233-244, 2016, PMID:27782328

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Protection of host cells by complement regulators.

Schmidt Christoph Q, Lambris John D, Ricklin Daniel, Immunological reviews 274(1): 152-171, 2016, PMID:27782321

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Preformed mediators of defense-Gatekeepers enter the spotlight.

Ricklin Daniel, Lambris John D, Immunological reviews 274(1): 5-8, 2016, PMID:27782322

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Complement component C3 - The "Swiss Army Knife" of innate immunity and host defense.

Ricklin Daniel, Reis Edimara S, Mastellos Dimitrios C, Gros Piet, Lambris John D, Immunological reviews 274(1): 33-58, 2016, PMID:27782325

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Compstatin Cp40 blocks hematin-mediated deposition of C3b fragments on erythrocytes: Implications for treatment of malarial anemia.

Lindorfer Margaret A, Cook Erika M, Reis Edimara S, Ricklin Daniel, Risitano Antonio M, Lambris John D, Taylor Ronald P, Clinical immunology (Orlando, Fla.) 171(): 32-35, 2016, PMID:27546448

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