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, 2006-2006
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

American Association of Immunologists, 1982 - Present
Biochemical Society (UK), 1984 - 1990
American Association of Microbiologists, 1985 - 1985
Aegean Conferencers, 1990 - Present
Protein Society, 1990 - 1995
American Association for Advancement of Science, 1990 - 1990
American Society for Biochemistry and Molecular Biology, 1991 - 1995
International Society of Developmental & Comparative Immunology, 1991 - 1995
Panepirotic Federation of America, Canada, & Australia, 1995 - 1997
National Science Foundation, Greece, 1997 - 2000

Web Links


Selected Publications

C3-targeted therapy in periodontal disease: moving closer to the clinic.

Hajishengallis G, Hasturk H, Lambris JD, Contributing authors, Trends in Immunology 42(): 856-864., 2021

Phase 2a clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation.

Hasturk H, Hajishengallis G, Lambris JD, Mastellos DC, Yancopoulou D., J Clin Invest., 2021

C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.

Schmitz R, Fitch ZW, Schroder PM, Choi AY, Manook M, Yoon J, Song M, Yi JS, Khandelwal S, Arepally GM, Farris AB, Reis ES, Lambris JD, Kwun J, Knechtle SJ., Nature Communications 12(): 5456., 2021

Erythrocytes Identify Complement Activation in Patients with COVID-19

Lam LM, Reilly JP, Rux AH, Murphy S, Kuri-Cervantes L, Weisman A, Ittner CA, Pampena MB, Betts M, Wherry EJ, Song WC, Lambris JD, Meyer NJ, Cines DB, Mangalmurti NS., Am J Physiol Lung Cell Mol Physiol, 2021, PMID:34231390

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Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions

Kim BJ, Mastellos DC, Li Y, Dunaief JL, Lambris JD., Prog Retin Eye Res, 2021, PMID:33321207

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Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus

Doni A, Parente R, Laface I, Magrini E, Cunha C, Colombo FS, Lacerda JF, Campos A Jr, Mapelli SN, Petroni F, Porte R, Schorn T, Inforzato A, Mercier T, Lagrou K, Maertens J, Lambris JD, Bottazzi B, Garlanda C, Botto M, Carvalho A, Mantovani A., Nat Commun 12(): 3739, 2021, PMID:34145258

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Is complement the culprit behind COVID-19 vaccine-related adverse reactions?

Mastellos DC, Skendros P, Lambris JD., J Clin Invest 131(): e151092, 2021, PMID:33945504

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Complement mediates binding and procoagulant effects of ultra-large HIT immune complexes

Khandelwal S, Barnes A, Rauova L, Sarkar A, Rux AH, Yarovoi SV, Zaitsev S, Lambris JD, Myoung SS, Johnson A, Lee GM, Duarte M, Poncz M, Arepally GM, Cines DB., Blood, 2021, PMID:34189574

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C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera

Silva de França F, Villas-Boas IM, Cogliati B, Woodruff TM, Reis EDS, Lambris JD, Tambourgi DV., Front Immunol 12(): 652242, 2021, PMID:33936074

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CD14 inhibition improves survival and attenuates thrombo-inflammation and cardiopulmonary dysfunction in a baboon model of Escherichia coli sepsis

Keshari RS, Silasi R, Popescu NI, Regmi G, Chaaban H, Lambris JD, Lupu C, Mollnes TE, Lupu F., J Thromb Haemost 19(): 429, 2021, PMID:33174372

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