“Seemingly remote studies in basic science of immunology can lead to new therapeutics. That’s the promise of basic research.  But it also takes time, commitment and a lot of resources.” - Carl Ware, Ph.D.

Dr. Ware is Head of the Division of Molecular Immunology at LIAI and adjunct Professor of Biology at UC San Diego . Dr. Ware's research focuses on an important group of cytokines produced by white blood cells called tumor necrosis factors (TNF), which control inflammation and host defenses to pathogens. His laboratory is unraveling the molecular mechanisms of how persistent viruses evade immune defenses providing insight into how the immune response is regulated.

Dr. Ware completed his B.S. in 1974 and his Ph.D. in Molecular Biology and Biochemistry in 1979 at the University of California, Irvine. Dr. Ware began his postdoctoral work at the University of Texas Health Science Center in the Department of Biochemistry, and in 1981 he moved to the Dana-Farber Cancer Institute, Boston, Massachusetts, to complete his postdoctoral training. Dr. Ware returned to California as an Assistant Professor of Immunology at University of California, Riverside in 1982, advancing to full professor in 1992. In 1996, Dr, Ware joined the faculty at LIAI as a full Member and Head of the Division of Molecular Immunology.

Dr. Ware serves on several granting agencies and foundations supporting biomedical research including the Arthritis National Research Foundation, the Sandler Program in Asthma Research and the National Institutes of Health. In addition, he serves as Councilor for the International Cytokine Society and is past president of the International Congress on TNF related Cytokines. Dr. Ware is recipient of a National Merit Award from National Institute for Allergy and Infectious Diseases.

Dr. Carl Ware, Ph.D., and his team study cytokines, proteins that act as communication signals between white blood cells and surrounding tissues. Their goal is to understand the basic molecular and cellular processes of how cytokines regulate immunity to viruses and translate that information into new therapies to control persistent viral infections, autoimmune diseases, and cancer.

The laboratory focuses on cytokines related to tumor necrosis factor (TNF), one of more than 20 related proteins (TNF superfamily) believed to have important roles in the ability of the immune system to guard the body against harmful microbes. Dr. Ware is a leading authority in the field of cytokines, having discovered several members of the TNF superfamily and how these cytokines control inflammation.

When improperly produced, TNF causes painful inflammation associated with diseases such as arthritis. Drugs that block TNF have led to new clinical treatments for arthritis, and TNF inhibitors, such as Enbrel and Remicade, are now FDA-approved for use in rheumatoid arthritis and inflammatory bowel disease. These drugs, known as biologics, are the first generation of therapeutics directed at blocking TNF, but they are not effective in all patients and have serious side effects.

Members of Dr. Ware's laboratory are discovering new ways to modulate TNF-related cytokines that may benefit patients with autoimmune disease. As a result of this research, new biologics, directed to TNF related cytokines are being created that can modulate inflammation and immunity. Interestingly, these same cytokines can be used to induce immunity to pathogens, such as viruses and bacteria, or to cancer. Ongoing work in the laboratory is redirecting these cytokines to applications in infectious and malignant diseases.

Unconventional ligand activation of herpesvirus entry mediator signals cell survival. Proc Natl Acad Sci U S A. 2009

Cross-regulation between herpesviruses and the TNF superfamily members. Nat Rev Immunol. 2008

TNF-Related Cytokines in Immunity. Ch. 25, in: Fundamental Immunology. 6th edition pp 776-803.

A crucial role for HVEM and BTLA in preventing intestinal inflammation. J Exp Med. 2008

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis. Cytokine Growth Factor Rev. 2008

Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways. Immunol Rev. 2008

The Lymphotoxin-{beta} Receptor Is an Upstream Activator of NF-{kappa}B-mediated Transcription in Melanoma Cells. J Biol Chem. 2008

ICOS, CD40, and lymphotoxin beta receptors signal sequentially and interdependently to initiate a germinal center reaction. J Immunol. 2008

Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus. Cell Host Microbe. 2008

Structural determinants of herpesvirus entry mediator recognition by murine B and T lymphocyte attenuator. J Immunol. 2008

The Inhibitory HVEM-BTLA Pathway Counter Regulates Lymphotoxin Receptor Signaling to Achieve Homeostasis of Dendritic Cells. J Immunol. 2008

Alternative entry receptors for herpes simplex virus and their roles in disease. Cell Host Microbe. 2007

Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands. J Exp Med. 2007

A fourth IkappaB protein within the NF-kappaB signaling module. Cell. 2007

The DARC conspiracy - virus invasion tactics. Trends Immunol. 2006

Specific remodeling of splenic architecture by cytomegalovirus. PLoS Pathog. 2006

Restoring Immune Defenses via Lymphotoxin Signaling: Lessons from Cytomegalovirus. Immunol Res. 2006

A TRAFfic cop for host defense. Nat Immunol. 2006

Poxviruses aren't stuPYD. Immunity. 2005

Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway. Proc Natl Acad Sci U S A. 2005

RIGing a virus trap. Nat Med. 2005

A lymphotoxin-IFN-beta axis essential for lymphocyte survival revealed during cytomegalovirus infection. J Immunol. 2005

Enhanced apoptosis and tumor regression induced by a direct agonist antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 2. Clin Cancer Res. 2005

Intrinsic Lymphotoxin-beta Receptor Requirement for Homeostasis of Lymphoid Tissue Dendritic Cells. Immunity. 2005

LIGHT Is Constitutively Expressed on T and NK Cells in the Human Gut and Can Be Induced by CD2-Mediated Signaling. J Immunol. 2005

NETWORK COMMUNICATIONS: Lymphotoxins, LIGHT, and TNF. Annu Rev Immunol. 2005

B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol. 2005

Lymphotoxin and LIGHT signaling pathways and target genes. Immunol Rev. 2004

LIGHT expression by mucosal T cells may regulate IFN-gamma expression in the intestine. J Immunol. 2004

TNF receptor-associated factor 5 limits the induction of Th2 immune responses. J Immunol. 2004

Structurally distinct recognition motifs in lymphotoxin-beta receptor and CD40 for tumor necrosis factor receptor-associated factor (TRAF)-mediated signaling. J Biol Chem. 2003

Different cytokines induce surface lymphotoxin-alphabeta on IL-7 receptor-alpha cells that differentially engender lymph nodes and Peyer's patches. Immunity. 2002

The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity. 2002

Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction. J Immunol. 2001

Genomic Characterization of LIGHT Reveals Linkage to an Immune Response Locus on Chromosome 19p13.3 and Distinct Isoforms Generated by Alternate Splicing or Proteolysis. J Immunol. 2001

Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus detente. Immunity. 2001

Discrete signaling regions in the lymphotoxin-β receptor for TRAF binding, subcellular localization and activation of cell death and NFkB pathways. J Biol Chem. 2000

Cutting edge: a novel viral TNF receptor superfamily member in virulent strains of human cytomegalovirus. J Immunol. 1999

LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity. 1998

Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB. Proc Natl Acad Sci U S A. 1997

The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. Cell. 1995

A lymphotoxin-beta-specific receptor. Science. 1994

Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell. 1993

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