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.
Permanent link
> Perelman School of Medicine   > Faculty   > Details

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.

Our laboratory invented the use of complement inhibitors for therapeutic purposes; I am the founder of Amyndas Pharmaceuticals, which is developing complement inhibitors (including third-generation compstatin analogues such as AMY‑101) for clinical applications. Our laboratory also invented the compstatin technology licensed to Apellis Pharmaceuticals (4(1MeW)7W (also known as POT‑4 and APL‑1) and pegylated derivatives such as APL-9 and APL-2/Pegcetatoplan/Empaveli/Aspavelli/Syfovre which has been approved by FDA for paroxysmal nocturnal hemoglobinuria (PNH) and as the first treatment for Geographic Atrophy — an advanced stage of age-related macular degeneration that is a leading cause of blindness.

For updated information please visit WWW.LAMBRIS.COM

Selected Publications

Mastellos DC, Hajishengallis G, Lambris JD.: A guide to complement biology, pathology and therapeutic opportunity. Nat Rev Immunol Sep 2023.

Li X, Wang H, Schmidt CQ, Ferreira VP, Yancopoulou D, Mastellos DC, Lambris JD, Hajishengallis G.: The Complement-Targeted Inhibitor Mini-FH Protects against Experimental Periodontitis via Both C3-Dependent and C3-Independent Mechanisms. J Immunol 211: 453-461, Aug 2023.

Gerogianni A, Bal M, Mohlin C, Woodruff TM, Lambris JD, Mollnes TE, Sjöström DJ, Nilsson PH.: In vitro evaluation of iron oxide nanoparticle-induced thromboinflammatory response using a combined human whole blood and endothelial cell model. Front Immunol 14: 1101387, Apr 2023.

Kuhn A, Riegger J, Teixeira GQ, Huber-Lang M, Lambris JD, Neidlinger-Wilke C, Brenner RE.: Terminal Complement Activation Is Induced by Factors Released from Endplate Tissue of Disc Degeneration Patients and Stimulates Expression of Catabolic Enzymes in Annulus Fibrosus Cells. Cells 12: 887, Mar 2023.

Bechtler C, Koutsogiannaki S, Umnyakova E, Hamid A, Gautam A, Sarigiannis Y, Pouw RB, Lamers C, Rabbani S, Schmidt CQ, Lambris JD, Ricklin D.: Complement-regulatory biomaterial coatings: Activity and selectivity profile of the factor H-binding peptide 5C6. Acta Biomater 155: 123-138, Jan 2023.

Lamers C, Ricklin D, Lambris JD.: Complement-targeted therapeutics: An emerging field enabled by academic drug discovery. Am J Hematol 2023.

Wang H, Ideguchi H, Kajikawa T, Mastellos DC, Lambris JD, Hajishengallis G.: Complement Is Required for Microbe-Driven Induction of Th17 and Periodontitis. J Immunol 209: 1370-1378, Oct 2022.

Lamers C, Xue X, Smieško M, van Son H, Wagner B, Berger N, Sfyroera G, Gros P, Lambris JD, Ricklin D.: Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors. Nat Commun 13: 5519, Sep 2022.

Skendros P, Germanidis G, Mastellos DC, Antoniadou C, Gavriilidis E, Kalopitas G, Samakidou A, Liontos A, Chrysanthopoulou A, Ntinopoulou M, Kogias D, Karanika I, Smyrlis A, Cepaityte D, Fotiadou I, Zioga N, Mitroulis I, Gatselis NK, Papagoras C, Metallidis S, Milionis H, Dalekos GN, Willems L, Persson B, Manivel VA, Nilsson B, Connolly ES, Iacobelli S, Papadopoulos V, Calado RT, Huber-Lang M, Risitano AM, Yancopoulou D, Ritis K, Lambris JD.: Complement C3 inhibition in severe COVID-19 using compstatin AMY-101. Sci Adv 8: eabo2341, Aug 2022.

Mastellos DC, Lambris JD.: Recent developments in C3-targeted complement therapeutics. Semin Immunol Jul 2022.

back to top
Last updated: 11/19/2023
The Trustees of the University of Pennsylvania