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
Inventor of the Year Award, Penn Center of Innovation, 2017
Patent Award, Penn Center of Innovation, 2018

Memberships and Professional Organizations

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

Web Links


Selected Publications

C3 glomerulopathy - understanding a rare complement-driven renal disease

Smith RJ, Appel GB, Blom AM, Cook HT, D'Agati VD, Fakhouri F, Fremeaux-Bacchi V, Józsi M, Kavanagh D, Lambris JD, Noris M, Pickering MC, Remuzzi G, de Córdoba SR, Sethi S, Van der Vlag J, Zipfel PF, Nester CM, Nature Reviews Nephrology 15(3): 129, 2019, PMID:30692664

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Taming hemodialysis-induced inflammation: Are complement C3 inhibitors a viable option?

Mastellos DC, Reis ES, Biglarnia AR, Waldman M, Quigg RJ, Huber-Lang M, Seelen MA, Daha MR, Lambris JD, Clin. Immunology 198(): 102, 2019, PMID:30472267

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Reduced Terminal Complement Complex Formation in Mice Manifests in Low Bone Mass and Impaired Fracture Healing.

Mödinger Y, Rapp AE, Vikman A, Ren Z, Fischer V, Bergdolt S, Haffner-Luntzer M, Song WC, Lambris JD, Huber-Lang M, Neidlinger-Wilke C, Brenner RE, Ignatius A., Am J Pathol. 189(1): 147, 2019, PMID:30339839

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Factor H interfers with the adhesion of sickle red cells to vascular endothelium: a novel disease modulating molecule.

Lombardi E, Matte A, Risitano AM, Ricklin D, Lambris JD, De Zanet D, Jokiranta ST, Martinelli N, Scambi C, Salvagno G, Bisoffi Z, Colato C, Siciliano A, Bortolami O, Mazzuccato M, Zorzi F, De Marco L, De Franceschi L, Haematologica, 2019, PMID:30630982

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Short Leucine-Rich Proteoglycans Modulate Complement Activity and Increase Killing of the Respiratory Pathogen Moraxella catarrhalis.

Laabei M, Liu G, Ermert D, Lambris JD, Riesbeck K, Blom AM., J. Immunology 201(9): 2721, 2018, PMID:30266767

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Complement C5a-Mediated TAM-ing of Antitumor Immunity Drives Squamous Carcinogenesis

Dimitrios C.Mastellos, Edimara S.Reis, John D.Lambris, Cancer Cell 34(4): 531, 2018

Safety profile after prolonged C3 inhibition.

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, Clinical Immunology, 2018, PMID:30217791

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Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis.

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, Journal of Proteome Research 17(9): 3153-3175, 2018, PMID:30111112

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Novel Immunoassay for Complement Activation by PF4/Heparin Complexes.

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, Thrombosis and Haemostasis 118(8): 1484-1487, 2018, PMID:29960275

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Expanding Complement Therapeutics of the Treatment of Proxysmal Nocturnal Hemoglobinuris

Mastellos DC, Reis ES, Yancopoulou D, Risitano AM, Lambris JD, Seminars in Hematology 55(3): 167, 2018, PMID:30032754

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