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
Long-term Fellowship from European Molecular Biology Organization ALTF 121-1982, 1982-1983
Fellowship from Alexander von Humboldt Foundation. This fellowship was declined in favor of the EMBO long-term fellowship, 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
Protein Society, 1990 - 1995
American Association for Advancement of Science, 1990 - 1990
Aegean Conferencers, 1990 - Present
International Society of Developmental & Comparative Immunology, 1991 - 1995
American Society for Biochemistry and Molecular Biology, 1991 - 1995
Panepirotic Federation of America, Canada, & Australia, 1995 - 1997
National Science Foundation, Greece, 1997 - 2000

Web Links


Selected Publications

The first case of COVID-19 treated with the complement C3 inhibitor AMY-101

Mastaglio, S, Ruggeri, A, Risitano, AM, Angelillo, P, Yancopoulou, D, Mastellos, DC, Huber-Lang, M, Piemontese, S, Assanelli, A, Garlanda, C, Lambris, JD, Ciceri, F, clinical immunology 215(): , 2020

Complement as a target in COVID-19?

Risitano, AM, Mastellos, DC, Huber-Lang, M, Yancopoulou, D, Garlanda, C, Ciceri, F, Lambris, JD, nature reviews immunology 20(6): 343-344, 2020

Prolonged intraocular residence and retinal tissue distribution of a fourth-generation compstatin-based C3 inhibitor in non-human primates

Hughes, S, Gumas, J, Lee, R, Rumano, M, Berger, N, Gautam, AK, Sfyroera, G, Chan, AL, Gnanaguru, G, Connor, KM, Kim, BJ, Dunaief, JL, Ricklin, D, Hajishengallis, G, Yancopoulou, D, Reis, ES, Mastellos, DC, Lambris, JD, clinical immunology 214(): , 2020

Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells

Baas, I, Delvasto-Nunez, L, Ligthart, P, Brouwer, C, Folman, C, Reis, ES, Ricklin, D, Lambris, JD, Wouters, D, de Haas, M, Jongerius, I, Zeerleder, SS, haematologica 105(2): E57-E60, 2020

Editorial: Therapeutic Modulation of the Complement System: Clinical Indications and Emerging Drug Leads

Mastellos, DC, Reis, ES, Lambris, JD, frontiers in immunology 10(): , 2020

''Stealth'' corporate innovation: an emerging threat for therapeutic drug development

Mastellos, DC, Blom, AM, Connolly, ES, Daha, MR, Geisbrecht, BV, Ghebrehiwet, B, Gros, P, Hajishengallis, G, Holers, VM, Huber-Lang, M, Kinoshita, T, Mollnes, TE, Montgomery, RA, Morgan, BP, Nilsson, B, Pio, R, Ricklin, D, Risitano, AM, Taylor, RP, Mantovani, A, Ioannidis, JPA, Lambris, JD, nature immunology 20(11): 1409-1413, 2019

Complement activation on neutrophils initiates endothelial adhesion and extravasation

Akk, A, Springer, LE, Yang, LH, Hamilton-Burdess, S, Lambris, JD, Yan, HM, Hu, Y, Wu, XB, Hourcade, DE, Miller, MJ, Pham, CTN, molecular immunology 114(): 629-642, 2019

Clinical promise of next-generation complement therapeutics

Mastellos, DC, Ricklin, D, Lambris, JD, nature reviews drug discovery 18(9): 707-729, 2019

Cholesterol Crystals Induce Coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor

Gravastrand, CS, Steinkjer, B, Halvorsen, B, Landsem, A, Skjelland, M, Jacobsen, EA, Woodruff, TM, Lambris, JD, Mollnes, TE, Brekke, OL, Espevik, T, Rokstad, AMA, journal of immunology 203(4): 853-863, 2019

New insights into the immune functions of complement

Reis, ES, Mastellos, DC, Hajishengallis, G, Lambris, JD, nature reviews immunology 19(8): 503-516, 2019

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