John D. Lambris, Ph.D.

faculty photo
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.NET

Selected Publications

Mastellos Dimitrios C, Ricklin Daniel, Lambris John D: Clinical promise of next-generation complement therapeutics. Nature reviews. Drug discovery Jul 2019.

Gravastrand Caroline S, Steinkjer Bjørg, Halvorsen Bente, Landsem Anne, Skjelland Mona, Jacobsen Eva Astrid, Woodruff Trent M, Lambris John D, Mollnes Tom E, Brekke Ole-Lars, Espevik Terje, Rokstad Anne Mari A: Cholesterol Crystals Induce Coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor. Journal of immunology (Baltimore, Md. : 1950) Jul 2019.

Baas Inge, Delvasto-Nuñez Laura, Ligthart Peter, Brouwer Conny, Folman Claudia, Reis Edimara S, Ricklin Daniel, Lambris John D, Wouters Diana, de Haas Masja, Jongerius Ilse, Zeerleder Sacha S: Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells. Haematologica Jun 2019.

Hudgens Jeffrey W, Gallagher Elyssia S, Karageorgos Ioannis, Anderson Kyle W, Filliben James J, Huang Richard Y-C, Chen Guodong, Bou-Assaf George M, Espada Alfonso, Chalmers Michael J, Harguindey Eduardo, Zhang Hui-Min, Walters Benjamin T, Zhang Jennifer, Venable John, Steckler Caitlin, Park Inhee, Brock Ansgar, Lu Xiaojun, Pandey Ratnesh, Chandramohan Arun, Anand Ganesh Srinivasan, Nirudodhi Sasidhar N, Sperry Justin B, Rouse Jason C, Carroll James A, Rand Kasper D, Leurs Ulrike, Weis David D, Al-Naqshabandi Mohammed A, Hageman Tyler S, Deredge Daniel, Wintrode Patrick L, Papanastasiou Malvina, Lambris John D, Li Sheng, Urata Sarah: Interlaboratory Comparison of Hydrogen-Deuterium Exchange Mass Spectrometry Measurements of the Fab Fragment of NISTmAb. Analytical chemistry 91(11): 7336-7345, Jun 2019.

Park Dong Ho, Connor Kip M, Lambris John D: The Challenges and Promise of Complement Therapeutics for Ocular Diseases. Frontiers in immunology 10: 1007, May 2019.

Reis Edimara S, Mastellos Dimitrios C, Hajishengallis George, Lambris John D: New insights into the immune functions of complement. Nature reviews. Immunology May 2019.

Karasu Ebru, Nilsson Bo, Köhl Jörg, Lambris John D, Huber-Lang Markus: Corrigendum: Targeting Complement Pathways in Polytrauma- and Sepsis-Induced Multiple-Organ Dysfunction. Frontiers in immunology 10: 994, May 2019.

Pio Ruben, Ajona Daniel, Ortiz-Espinosa Sergio, Mantovani Alberto, Lambris John D: Complementing the Cancer-Immunity Cycle. Frontiers in immunology 10: 774, Apr 2019.

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: C3 glomerulopathy - understanding a rare complement-driven renal disease. Nature Reviews Nephrology 15(3): 129, Mar 2019.

Karasu Ebru, Nilsson Bo, Köhl Jörg, Lambris John D, Huber-Lang Markus: Targeting Complement Pathways in Polytrauma- and Sepsis-Induced Multiple-Organ Dysfunction. Frontiers in immunology 10: 543, Mar 2019.

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Last updated: 10/19/2019
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