Dr. Ley joined LIAI in 2007 as the founding Division Head of the Division of Inflammation Biology. Dr. Ley received his B.S. from Altkönigschule-Gymnasium, Kronberg, Germany in 1976. In 1982, he received his M.D. from the Julius-Maximilians-Universität, Würzburg, Germany. Dr. Ley began his postdoctoral training from 1983 to 1987 at the Freie Universität Berlin, Germany. From 1987 to 1989, Dr. Ley was a visiting research scientist at the University of California, San Diego and returned to Freie Universität Berlin until 1994, when he joined the faculty of the University of Virginia. From 2001-2007, he was director of the Robert M Berne Cardiovascular Research Center at the University of Virginia.
Klaus Ley, M.D., and his team study inflammation as a defense reaction caused by tissue damage or injury, characterized by redness, heat, swelling, and pain. The primary objective of inflammation is to localize and eradicate the irritant and repair the surrounding tissue. For the survival of the host, inflammation is a necessary and beneficial process. The inflammatory response involves three major stages: first, dilation of capillaries to increase blood flow; second, microvascular structural changes and escape of plasma proteins from the bloodstream; and third, leukocyte transmigration through endothelium and accumulation at the site of injury.
The leukocyte adhesion cascade is a sequence of adhesion and activation events that ends with extravasation of the leukocyte, whereby the cell exerts its effects on the inflamed site. Dr Ley has investigated the roles of adhesion molecules in acute and chronic inflammation with the ultimate goal to develop methods to control inflammation. One application is in atherosclerosis, the disease of the vessel wall that underlies heart attacks and strokes. Dr. Ley’s team is working on developing a vaccine against atherosclerosis. They have developed a vaccine that is effective in mice and are now aiming at translating this to a vaccine for humans.
From The Lab
Engineered red blood cells can relieve autoimmune diseases, study finds
Our perpetually vigilant internal guardian
La Jolla Institute researcher honored with 2016 Distinguished Scientist Award from American Heart Association
LJI researchers gain new understanding of how neutrophils latch onto vessel walls to protect from infection and clean up injured tissue
Neutrophil recruitment: from model systems to tissue-specific patterns
Circulating T cell-monocyte complexes are markers of immune perturbations
Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem
The trafficking protein JFC1 regulates Rac1-GTP localization at the uropod controlling neutrophil chemotaxis and in vivo migration
Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages
Loss of CXCR4 on non-classical monocytes in participants of the women's interagency HIV study (WIHS) with subclinical atherosclerosis
Vaccination against atherosclerosis
Myeloid-specific deletion of epsins 1 and 2 reduces atherosclerosis by preventing LRP-1 downregulation
Platelet serotonin aggravates myocardial ischemia/reperfusion injury via neutrophil degranulation
CX3CL1-Fc treatment prevents atherosclerosis in Ldlr KO mice
Immunity and inflammation in atherosclerosis
High-affinity bent beta2-integrin molecules in arresting neutrophils face each other through binding to ICAMs in cis
A single-step chemoenzymatic reaction for the construction of antibody-cell conjugates
Neutrophils: New insights and open questions
Atherosclerosis in the single-cell era
Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages
A clinically applicable adjuvant for an atherosclerosis vaccine in mice
Single-cell RNA-seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis
Atlas of the immune cell repertoire in mouse atherosclerosis defined by single-cell RNA-sequencing and mass cytometry
Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice
Transmission of integrin β7 transmembrane domain topology enables gut lymphoid tissue development
Regulatory CD4+ T cells recognize MHC-II-restricted peptide epitopes of apolipoprotein B
Inflammatory pathways regulated by tumor-necrosis receptor associated factor 1 protect from metabolic consequences in diet-induced obesity
A ligand-specific blockage of the intgrin Mac-1 selectivitely targets pathologic inflammation while maintaining protective host-defense
Structure-function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8
Natural killer cells at ease: atherosclerosis is not affected by genetic depletion or hyperactivation of natural killer cells
Effector and regulatory T cells roll at high shear stress by inducible tether and sling formation
Patrolling mechanics of non-classical monocytes in vascular inflammation
M1 means kill; M2 means heal
Scavenger receptor CD36 directs nonclassical monocyte patrolling along the endothelium during early atherogenesis
Developing neutrophils must eat…themselves!
Rolling neutrophils form tethers and slings under physiologic conditions in vivo
Natural variation of macrophage activation as disease-relevant phenotype predictive of inflammation and cancer survival
Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis
IL-27R signaling controls myeloid cells accumulation and antigen-presentation in atherosclerosis
Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues
P-selection glycoprotein ligand-1 in T cells
ATVB distinguished scientist award: how costimulatory and coinhibitory pathways shape atherosclerosis
Defects in DNA replication hit NK cells and neutrophils
Atheroprotective vaccination with MHC-II-restricted ApoB peptides induces peritoneal IL-10-producing CD4 T cells
Breaking a vicious cycle
Leukocyte arrest: biomechanics and molecular mechanisms of β2 integrin activation
Macrophage polarization: decisions that affect health
Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis
Microfluidics-based side view flow chamber reveals tether-to0sling translation in rollin gneutrophils
Live cell imaging to understand monocyte, macrophage, and dendritic cell function in atherosclerosis
How mouse macrophages sense what is going on
Leukocyte adhesion deficiency IV. Monocyte integrin activation deficiency in cystic fibrosis
CCR5+T-bet+FoxP3+ effector CD4 T cells drive atherosclerosis
2015 russell ross memorial lecture in vascular biology: protective autoimmunity in atherosclerosis
Integrin-based therapuetics: biological basis, clinical use and new drugs
Gαi2 and Gαi3 differentially regulate arrest from flow and chemotaxis in mouse neutrophils
Protection from spetic peritonitis by rapid neutrophil recruitment through omental high endothelial venules
Gnb isoforms orchestrate a signaling pathway comprising Rac1, Plcβ2, and Plcβ3 leading to LFA-1 activation and neutrophil arrest in vivo
SLAT promotes TCR-mediated, Rap1-dependent LFA-1 activation and adhesion through interaction of its PH domain with Rap1
Role of the endothelial surface layer in neutrophil recruitment
Beyond vascular inflammation-recent advances in understanding atherosclerosis
Monocyte trafficking across the vessel wall
HGF guides T cells into the heart
Vaccination to modulate atherosclerosis
Sequential immune responses: the weapons of immunity
SAMP1/YitFc mice develop ileitis via loss of CCL21 and defects in dendritic cell migration
Monocyte phenotypes: when local education counts
Soluble CD163 is assocaited with noninvasive measures of liver fibrosis in hepatitis C virus- and hepatitis C virus/human immunodeficiency virus-infected woman
Intravital live cell triggered imaging system reveals monocyte patrolling and macrophage migration in atherosclerotic arteries
Macrophages at the fork in the road to health or disease
Lymphocyte migration into atherosclerotic plaque
Waking up the stem cell niche: how hematopoietic stem cells generate inflammatory monocytes after stroke
Genetic deletion of platelet glycoprotein Ib alpha but not its extracellular domain protects from atherosclerosis
L-selectin deficiency decreases aortic B1a and Breg subsets and promotes atherosclerosis
M1 and M2 microphages: the chicken and the egg of immunity
Fueling the fire: src family kinases drive inflammation
The second touch hypothesis: T cell activation, homing and polarization
Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus of hepatitis c virus infection
Atheroprotective vaccination with MHC-II restricted peptides from ApoB-100
T cells in atherosclerosis
Dysregulated NOD2 predisposes SAMP1/YitFc mice to chronic intestinal inflammation
Myeloid cells in atherosclerosis: a delicate balance of anti-inflammatory and proinflammatory mechanisms
Leukocytes talking to VE-cadherin
The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow
Increased atherosclerotic lesion formation and vascular leukocyte accumulation in renal impairment are mediated by interleukin 17A
Bacterial colonization facturs control specificity and stability of the gut microbiora
Neutrophil rolling at high shear: flattening, catch bond behavior, tethers and slings
The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunigy
Increased cholesterol content in gammadelta (γδ) T lymphocytes differentially reguates their activationIncreased cholesterol content in gammadelta (γδ) T lymphocytes differentially reguates their activation
Quantitative dynamic footprinting microscopy
Interleukin-27 receptor limits atherosclerosis in Ldlr-/- mice
Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis
Interleukin-17 ssignaling in inflammatory cells, kupffer, and hepatic stellate cells exacerabtes liver fibrosis in mice
Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury
Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses
Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice
Slings' enable neutrophil rolling at high shear
Global metabolic inhinitors of sialyl- and fucosyltransferases remodel the glycome
Transforming growth factor-β: transforming plaque to stability
Neutrophil arrest by LFA-1 activation
Severe impairment of leukocyte recruitment in ppGalNAcT-1 deficient mice
Distinct roles for talin-1 and kindlin-3 in LFA-1 extension and affinity regulation
Protective role for myeloid specific KLF2 in atherosclerosis
Neutrophilic granulocytes modulate invariant NKT cell function in mice and humans
Regulation of neutrophil function by adenosine
Protein kinase C-θ is required for murine neutrophil recruitment and adhesion strengthening under flow
Accelerated atherosclerosis in apoe-/- mice heterozygous for the insulin receptor and the insulin receptor substrate-1
NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis
B-cell aortic homing and atheroprotection depend on Id3
Biomechanics of leukocyte rolling
SAMP1/YitFc mouse strain: A spontaneous model of Chron's disease-like ileitis
Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow
How dendritic cells shape atherosclerosis
CD63 positions CD62P for rolling
High refractive index silicone gels for simultaneous total internal reflection flourescence and traction force microscopy of adherent cells
Small molecule-mediated activation of the integrin CD11b/CD18 reduces inflammatory disease
Monocyte and macrophage dynamics during atherogenesis
Flow cytometry analysis of immune cells within murine aortas
Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling
Live cell imaging of paxillin in rolling neutrophils by dual-color quantitative dynamic footprinting
Adam 17-dependent shedding limits early neutrophil influx but does not alter early monocyte recruitment to inflammatory sites
Protein tyrosine kinases in neutrophil activation and recruitment
Mycophenolate mofetil decreases atherosclerotic lesion size by depression of aortic T lymphocyte and IL-17-mediated macrophage accumulation
Protein kinase C isoforms in neutrophil adhesion and activation
Cell protrusions and tethers: a unified approach
Prevention, but not cure of type 1 diabetes by FTY720 in NOD/LtJ mice despite effective modulation of blood T cells
Research Tech II
I graduated in 2012 from Berry College in Rome, GA with a B.S. in Chemistry. While in my undergraduate studies I researched T. cruzi under Dr. Chris Hall and studied organic methodology focusing on phosphonic acid poromoted aldol-type reactions between imines and unactivated aldehydes under Dr. Lindsey Davis.
After graduation I worked for a small chemical company focusing on adsorbed natural gas utilizing nanoporous carbon, and then transitioned to a cGMP environment at the biotech company Dendreon. I worked at Dendreon for 4 years in the QC Bioassay lab as a back-up shift lead and QC analyst performing release testing (ELISA, Endo, FACS, NC-200, Gram Stain) on the FDA approved Autologous Immunotherapy (AIT) Provenge Sipuleucel-T.
I also worked for Yokogawa as an Application Engineer specializing in advanced analytical systems such as the Tunable Diode Laser Spectrometer TDLS. I joined the Ley Lab in August 2018 with the intention to expand my knowledge of immunology and pursue the competitive field of NGS and RNAseq.
Zhichao Fan, Ph.D.
I graduated from Soochow University, China in 2008 with a B.S. degree in Biotechnology. I then obtained my Ph.D. in Biomedical Optics and Chemical Biology from the Fudan University, China in 2013. I began working as a postdoc in the Ley laboratory at the La Jolla Institute for Immunology in August 2013.
Research Focus: My research projects are focused on the mechanisms of leukocyte rolling and arrest during inflammation in the microcirculation. I am interested in understanding the mechanism of integrin activation happen underline leukocyte arrest. I exploited microfluidics with molecularly defined surfaces and high resolution three-color total internal reflection microscopy to imaging the molecular dynamics during leukocyte rolling and arrest under high resolution in vitro, and using intravital microscopy to study leukocyte rolling and arrest in vivo.
I plan to pursue a career in scientific research focused on molecular mechanism involved in integrin activation, leukocyte adhesion and developing advanced optical imaging techniques.
I am currently an undergraduate at the University of California: San Diego studying Bioengineering: Bioinformatics. I am interested in studying and developing computational approaches to answer open questions in biology and immunology.
I hope to pursue a PhD in Quantitative or Computational Biology and continue researching topics in immunology and genetics.
Research Tech II
Yun Min Jung
I graduated from Tokyo University of Pharmacy and Life Science in 2003. I obtained my Ph.D. from Yokohama City University Graduate School of Medicine in 2009. I started postdoctoral work in the Dr. Horii’s laboratory at the Research Institute for Microbial Diseases, Osaka University from April 2009 to March 2010. I then worked as a staff scientist in the Laboratory of Adjuvant Innovation at the National Institutes of Biomedical Innovation, Health and Nutrition until August 2015 (Dr. Ishii’s laboratory). I began working as a postdoc in the Dr. Ley laboratory at the La Jolla Institute for Immunology in September 2015.
My research interests focus on innate immunity and vaccine adjuvant. My research project is the development and optimization of non-communicable diseases vaccine especially atherosclerosis using several adjuvants. I want to know which kind of adjuvant is required and which type of immune responses should be regulated by adjuvant for atherosclerosis vaccine.
I plan to pursue a career in scientific research focused on vaccine adjuvant to develop concepts of effective and safety vaccine against infectious and non-communicable diseases.
Marco Orecchioni, Ph.D.
Research Tech I
Postdoc Fellow (0 year)
I completed my PhD in Medical Science from Lund University, Sweden, in June 2018; in the subject of Biomedicine and Experimental Cardiovascular Research. During my studies, I worked with immune responses against modified extracellular matrix proteins in atherosclerosis, cardiovascular disease and diabetes. After my dissertation, I worked as a researcher within cardiovascular immunology in the same lab.
I joined the Ley Lab at La Jolla Institute for Immunology as a postdoctoral fellow in March 2019, where I will characterize and phenotype T cell subsets in cardiovascular disease subjects.
I graduated from RWTH Aachen University, Germany, with a M.Sc. (Diplom) degree in Biology. Afterwards I moved to Munich and obtained my Ph.D. (Dr. rer. nat.) in January 2017 at the Institute for Cardiovascular Prevention (IPEK), LMU Munich, Germany. Simultaneously, I could pursue my research projects at the Department for Medical Biochemistry, Academic Medical Center (AMC) Amsterdam, The Netherlands.
During my undergraduate studies I became fascinated by the adaptive immune system. This led me to study T cell activation in atherosclerosis during my master’s thesis and the role of costimulation in this chronic inflammatory disorder of the vasculature during my Ph.D. thesis. In September 2016 I joined Dr. Ley’s group as a postdoctoral fellow at the La Jolla Institute for Immunology.
My current project focuses on how T cell responses, especially regulatory T cells, are involved in initiation and progression of atherosclerosis. This includes studying the fate and plasticity of these T cells and to what extent their phenotype changes in the progression of disease. Furthermore, I want to understand whether immunomodulatory therapies can alter the phenotype of T cells towards a beneficial T cell response leading to ameliorated atherosclerosis.
I want to pursue a career in scientific research focusing on the understanding of the adaptive immune response in cardiovascular disease allowing to design better therapeutical treatments for patients.
Dennis Wolf, MD
I graduated from Medical School at the University of Freiburg, Germany, in 2007 and worked as a research assistant at the BakerIDI Heart and Diabetes Institute, Melbourne, from 2007 to 2008. I obtained my MD in 2011 at the University of Freiburg for my work on inflammatory leukocyte recruitment in atherosclerosis. In 2009 I started as clinical resident in cardiology at the University Heart Center in Freiburg and obtained my certificate in internal medicine. In 2014 I started as a postdoctoral fellow at the La Jolla Institute for Immunology in October 2014.
My research interest focusses on inflammatory and immune mechanisms in cardio-metabolic disease, such as in atherosclerosis and the metabolic syndrome. In particular, I am interested in understanding how immune cells and their effector functions contribute to disease initiation and progression. Currently, I am working on the adaptive immune response in atherosclerosis to understand how particular antigens drive a beneficial or harmful T-helper cell response.
I plan to pursue a career as physician-scientist with a focus on clinical cardiology and on basic research in human cardiovascular disease.