Charles E. Egwuagu, Ph.D.

Senior Investigator:

Research interests: Molecular immunology

Contact Information: 301-496-0049

Building 10, Room 10N248G
10 Center Drive
Bethesda, Maryland 20892

Biography

Dr. Charles E. Egwuagu is an Epidemiologist/Immunologist and Chief of the Molecular Immunology Section, National Eye Institute. He received his Ph.D. and M.Phil. from Yale University and an M.P.H from the Yale School of Medicine, New Haven, Connecticut. Dr. Egwuagu then served as a Commissioned Officer of the USA Public Health Service, attaining the rank of Captain (06). Major research focus in the Egwuagu laboratory is on autoreactive lymphocytes that mediate CNS autoimmune diseases, such as Uveitis and Multiple Sclerosis. Particular interest is on cytokine signaling and epigenetic mechanisms that regulate lymphocyte development and cell-fate decisions. The ultimate goal is to develop Biologics and autologous regulatory B cell (Breg) immunotherapy for autoimmune and neurodegenerative diseases.

Current research


The main thrust of research in the Molecular Immunology Section is to understand molecular and cellular mechanisms that regulate host immunity, with particular emphasis on: (i) Mechanisms that regulate lymphocyte development and cell-fate decisions; (ii) Developing Biologics that target lymphocyte signaling pathways for use in treating CNS inflammatory diseases, such as Uveitis and Multiple Sclerosis. Major Areas of Investigation and Findings (i)Cellular/molecular mechanisms that mediate or suppress ocular inflammatory diseases (uveitis) Ocular inflammatory diseases are a major cause of severe visual handicap in the USA and include sight-threatening idiopathic inflammatory ocular diseases such as Scleritis and Uveitis. T lymphocytes are currently thought to be the etiologic agents. Our studies have implicated Th17 cells as a pathogenic T cell subset that mediates Uveitis or Scleritis while IL-10- and IL-35-producing regulatory B cells (Bregs) suppress Uveitis and mitigate ocular pathology. A great deal of our effort is aimed at understanding factors that promote Th17-mediated uveitis and mechanisms by which Breg cells mitigate ocular pathology. (ii)Development of Biologics and Regulatory B cell (Breg) therapy for autoimmune diseases Interleukin 12 (IL-12) cytokines play critical roles in initiating adaptive immune responses. They also regulate the intensity, duration and quality of innate and adaptive immune responses. However, unbridled activation of immune cells by IL-12 cytokines is implicated in the development of autoimmune diseases. Each of its 4 members is comprised of an alpha and beta chain, with some members (IL-12, IL-23) promoting inflammation and autoimmune pathology while others (IL-27, IL-35) suppress inflammation and limit tissue injury. IL-12 family cytokines regulate the differentiation and effector functions of lymphoid and myeloid cell types through the activation of JAK/STAT pathways and duration of the STAT signal is under stringent negative feedback regulation by suppressor of cytokine signaling 1 (SOCS1) and SOCS3. Our drug discovery program to identify effective immune-suppressive Biologics focus on: Utilizing membrane-penetrating JAK inhibitors and SOCS1 or SOCS3 mimetic peptides to target JAK/STAT pathways that activate pro-inflammatory effector functions of pathogenic lymphocytes. Genetic engineering of each ?? and ?? IL-12 subunit protein and novel combinations of these subunits for use as Biologics and potential therapeutic cytokines to regulate inflammation. Our bioengineered recombinant IL-35 suppresses autoimmune diseases. Our IL-35 studies led to our discovery of IL-10-producing Breg cells and a novel Breg cells that produce IL-35 (i35-Breg). Both Breg types suppress CNS autoimmune diseases by antagonizing pathogenic Th17 responses.

Selected publications

Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE. 

Egwuagu CE, Yu CR.

He C, Yu CR, Sun L, Mahdi RM, Larkin J 3rd, Egwuagu CE.

Dambuza IM, He C, Choi JK, Yu CR, Wang R, Mattapallil MJ, Wingfield PT, Caspi RR, Egwuagu CE. 

Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, Wingfield PT, Kim SH, Egwuagu CE. 

Last updated: July 10, 2019