John D. Lambris, Ph.D.

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Dr. Ralph and Sallie Weaver Professor of Research Medicine
Department: Pathology and Laboratory Medicine

Contact information
401 Stellar-Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Office: (215) 746-5765
Fax: (215) 573-8738
B.S. (Biology)
University of Patras, Greece, 1976.
Ph.D. (Biochemistry)
University of Patras, Greece, 1979.
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Description of 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.COM

Selected Publications

Hajishengallis G, Hasturk H, Lambris JD, Contributing authors: C3-targeted therapy in periodontal disease: moving closer to the clinic. Trends in Immunology 42: 856-864. Oct 2021.

Hasturk H, Hajishengallis G, Lambris JD, Mastellos DC, Yancopoulou D.: Phase 2a clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. Oct 2021.

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.: C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates. Nature Communications 12: 5456. Sep 2021.

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.: Erythrocytes Identify Complement Activation in Patients with COVID-19. Am J Physiol Lung Cell Mol Physiol Jul 2021.

Kim BJ, Mastellos DC, Li Y, Dunaief JL, Lambris JD.: Targeting complement components C3 and C5 for the retina: Key concepts and lingering questions. Prog Retin Eye Res Page: 100936, Jul 2021.

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.: Complement mediates binding and procoagulant effects of ultra-large HIT immune complexes. Blood Jun 2021.

Mastellos DC, Skendros P, Lambris JD.: Is complement the culprit behind COVID-19 vaccine-related adverse reactions? J Clin Invest 131: e151092, Jun 2021.

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.: Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus. Nat Commun 12: 3739, Jun 2021.

Silva de França F, Villas-Boas IM, Cogliati B, Woodruff TM, Reis EDS, Lambris JD, Tambourgi DV.: C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera. Front Immunol 12: 652242, Apr 2021.

Keshari RS, Silasi R, Popescu NI, Regmi G, Chaaban H, Lambris JD, Lupu C, Mollnes TE, Lupu F.: CD14 inhibition improves survival and attenuates thrombo-inflammation and cardiopulmonary dysfunction in a baboon model of Escherichia coli sepsis. J Thromb Haemost 19: 429, Feb 2021.

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Last updated: 11/04/2021
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