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
Education:
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.NET

Selected Publications

Huber-Lang M, Lambris JD, Ward PA: Innate immune responses to trauma. Nature Immunology Mar 2018.

Mukai R, Okunuki Y, Husain D, Kim CB, Lambris JD, Connor KM: The Complement System Is Critical in Maintaining Retinal Integrity during Aging. Frontiers in Aging Neuroscience 10(15), Feb 2018.

Ricklin D, Mastellos DC, Reis ES, Lambris JD.: The renaissance of complement therapeutics. Nature Reviews. Nephrology 14(1): 26-47, Jan 2018.

Kwak JW, Laskowski J, Li HY, McSharry MV, Sippel TR, Bullock BL, Johnson AM, Poczobutt JM, Neuwelt AJ, Malkoski SP, Weiser-Evans MC, Lambris JD, Clambey ET, Thurman JM, Nemenoff RA.: Complement Activation via a C3a Receptor Pathway Alters CD4+ T Lymphocytes and Mediates Lung Cancer Progression. Cancer Research 78(1): 143-156, Jan 2018.

van Griensven M, Ricklin D, Denk S, Halbgebauer R, Braun CK, Schultze A, Hönes F, Koutsogiannaki S, Primikyri A, Reis E, Messerer D, Hafner S, Radermacher P, Biglarnia AR, Resuello RRG, Tuplano JV, Mayer B, Nilsson K, Nilsson B, Lambris JD, Huber-Lang M.: Protective Effects of the Complement Inhibitor Compstatin CP40 in Hemorrhagic Shock. Shock Page: Feb, 2018.

Blom AM, Magda M, Kohl L, Shaughnessy J, Lambris JD, Ram S, Ermert D.: Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen Streptococcus pyogenes. Journal of immunology 199: 3828-3839, Dec 2017.

Hajishengallis G, Reis ES, Mastellos DC, Ricklin D, Lambris JD.: Novel mechanisms and functions of complement. Nature Immunology. Nature Immunology 18(12): 1288-1298, Nov 2017.

Blatt AZ, Saggu G, Cortes C, Herbert AP, Kavanagh D, Ricklin D, Lambris JD, Ferreira VP: Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation. Frontiers in Immunology 8: 1586, Nov 2017.

Kovtun Anna, Bergdolt Stephanie, Hägele Yvonne, Matthes Rebekka, Lambris John D, Huber-Lang Markus, Ignatius Anita: Complement receptors C5aR1 and C5aR2 act differentially during the early immune response after bone fracture but are similarly involved in bone repair. Scientific Reports 7(1): 14061, Oct 2017.

Wang HongBin, Ricklin Daniel, Lambris John D: Complement-activation fragment C4a mediates effector functions by binding as untethered agonist to protease-activated receptors 1 and 4. Proceedings of the National Academy of Sciences of the United States of America 114(41): 10948-10953, Oct 2017.

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Last updated: 04/15/2018
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