Klaus Ley Lab

Who We Are

The Ley lab studies atherosclerosis, the pathomechanism underlying most cardiovascular disease. We focus on the adaptive immune system. We work on the autoimmune aspect of atherosclerosis, mainly on the CD4 and CD8 T cell responses.

Dr. Klaus Ley

Klaus Ley, M.D.

Founding Co-Director, Immunology Center of Georgia (IMMCG)
Georgia Research Alliance Bradley Turner Eminent Scholar in Immunology
Professor, Department of Physiology
Medical College of Georgia at Augusta University

What We Study

The lab uses human samples from patients with the disease we study: cardiovascular disease including coronary artery disease. Major methods we use:

Human blood leukocytes: single cell RNA sequencing with surface phenotype by CITE-Seq
Spectral flow cytometry
Bioinformatics: noise reduction methods, gene signatures
T cell receptor sequencing
Epitope identification

Cell type discovery
Lineage tracker mice
Reporter mice
Knockout and knockin mice
Intravital microscopy

Contact Us

Immunology Center of Georgia (IMMCG)

Health Sciences Campus

Georgia Cancer Center - M. Bert Storey Research Building

1410 Laney Walker Blvd, CN2119

kley@augusta.edu

706-446-0296

Research Team

Anusha Bellapu

Bioinformatician 2

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India

Michael Nakama, MS

Research Manager

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United States of America

Pei Xiong Liew, PhD

Senior Research Scientist

Singapore

Mikhail Fomin, MSc

Research Associate

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United States of America

Payel Roy, PhD

Assistant Research Scientist

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India

Qingkang Lyu, PhD

Postdoc

Chinese Flag

China

Mohammad Oliaeimotlagh, MD MSc

Postdoc

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Iran

Smriti Parashar, PhD

Postdoc

India flag

India

Sunil Kumar, Ph.D.

Postdoc

India flag

India

Yan Wang, PhD

Postdoc

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China

Megh Mehta

Graduate Research Assistant

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United States of America

Aderonke Fakayode

Graduate Research Assistant

Nigeria

Current Research Interests

High-dimensional data generated by single-cell RNA sequencing
Integrin activation in immune cells
Autoimmune response to ApoB and the potential to apply this to develop a vaccine for atherosclerosis
Understanding a newly discovered type of olfactory receptors in macrophages and their role in atherosclerosis
Understanding differences in the immune response of diverse populations to atherosclerosis

Publication
PD-1 and CD73 on naive CD4⁺ T cells synergistically limit responses to self Nettersheim, F. S., Brunel, S., Sinkovits, R. S., Armstrong, S. S., Roy, P., Billitti, M., Kobiyama, K., Alimadadi, A., Bombin, S., Lu, L., Zoccheddu, M., Oliaeimotlagh, M., Benedict, C. A., Sette, A. & Ley, K., 2024, (Accepted/In press) In: Nature Immunology. Research output: Contribution to journal › Article › peer-review
Olfr2-positive macrophages originate from monocytes proliferate in situ and present a pro-inflammatory foamy-like phenotype Suthahar, S. S. A., Nettersheim, F. S., Alimadadi, A., Wang, E., Billitti, M., Resto-Trujillo, N., Roy, P., Hedrick, C., Ley, K. & Orecchioni, M., Sep 1 2024, In: Cardiovascular Research. 120, 13, p. 1577-1589 13 p. Research output: Contribution to journal › Article › peer-review
Editorial: Adaptive immunity in atherosclerosis Slütter, B. & Ley, K., 2024, In: Frontiers in immunology. 15, 1440283. Research output: Contribution to journal › Editorial › peer-review
Mild Hypoxia Accelerates Cerebral Cavernous Malformation Disease Through CX3CR1-CX3CL1 Signaling Frias-Anaya, E., Gallego-Gutierrez, H., Gongol, B., Weinsheimer, S., Lai, C. C., Orecchioni, M., Sriram, A., Bui, C. M., Nelsen, B., Hale, P., Pham, A., Shenkar, R., Debiasse, D., Lightle, R., Girard, R., Li, Y., Srinath, A., Daneman, R., Nudleman, E. & Sun, H. & 8 others, Guma, M., Dubrac, A., Mesarwi, O. A., Ley, K., Kim, H., Awad, I. A., Ginsberg, M. H. & Lopez-Ramirez, M. A., Jun 1 2024, In: Arteriosclerosis, thrombosis, and vascular biology. 44, 6, p. 1246-1264 19 p. Research output: Contribution to journal › Article › peer-review
Identification of apolipoprotein B–reactive CDR3 motifs allows tracking of atherosclerosis-related memory CD4⁺T cells in multiple donors Roy, P., Suthahar, S. S. A., Makings, J. & Ley, K., 2024, In: Frontiers in immunology. 15, 1302031. Research output: Contribution to journal › Article › peer-review
Immunotherapy for atherosclerosis by targeting pro-inflammatory T cells Khan, A. & Ley, K., Jul 2024, In: Cell Research. 34, 7, p. 467-468 2 p. Research output: Contribution to journal › Article › peer-review
Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities Stroope, C., Nettersheim, F. S., Coon, B., Finney, A. C., Schwartz, M. A., Ley, K., Rom, O. & Yurdagul, A., Apr 2024, In: Nature Metabolism. 6, 4, p. 617-638 22 p. Research output: Contribution to journal › Review article › peer-review
Immune profiling and tracking of two-dimensional transition metal dichalcogenides in cells and tissues Gazzi, A., Fusco, L., Orecchioni, M., Keshavan, S., Shin, Y., Grivel, J. C., Rinchai, D., Ahmed, E. I., Elhanani, O., Furesi, G., Rauner, M., Keren, L., Ley, K., Casiraghi, C., Bedognetti, D., Fadeel, B. & Delogu, L. G., Feb 2024, In: Nano Today. 54, 102084. Research output: Contribution to journal › Article › peer-review
Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease Chatterjee, N., Komaravolu, R. K., Durant, C. P., Wu, R., McSkimming, C., Drago, F., Kumar, S., Valentin-Guillama, G., Miller, Y. I., McNamara, C. A., Ley, K., Taylor, A., Alimadadi, A. & Hedrick, C. C., Mar 2024, In: International journal of molecular sciences. 25, 5, 2894. Research output: Contribution to journal › Article › peer-review
Breaking tolerance: the autoimmune aspect of atherosclerosis Khan, A., Roy, P. & Ley, K., Sep 2024, In: Nature Reviews Immunology. 24, 9, p. 670-679 10 p. Research output: Contribution to journal › Article › peer-review
Single-cell profiling of CD11c+ B cells in atherosclerosis Pattarabanjird, T., Srikakulapu, P., Ransegnola, B., Marshall, M. A., Ghosheh, Y., Gulati, R., Durant, C., Drago, F., Taylor, A. M., Ley, K. & McNamara, C. A., 2023, In: Frontiers in immunology. 14, 1296668. Research output: Contribution to journal › Article › peer-review
Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease Iqneibi, S., Saigusa, R., Khan, A., Oliaeimotlagh, M., Armstrong Suthahar, S. S., Kumar, S., Alimadadi, A., Durant, C. P., Ghosheh, Y., McNamara, C. A., Hedrick, C. C. & Ley, K., 2023, In: Frontiers in immunology. 14, 1239148. Research output: Contribution to journal › Article › peer-review
Cell-autonomous regulation of complement C3 by factor H limits macrophage efferocytosis and exacerbates atherosclerosis Kiss, M. G., Papac-Miličević, N., Porsch, F., Tsiantoulas, D., Hendrikx, T., Takaoka, M., Dinh, H. Q., Narzt, M. S., Göderle, L., Ozsvár-Kozma, M., Schuster, M., Fortelny, N., Hladik, A., Knapp, S., Gruber, F., Pickering, M. C., Bock, C., Swirski, F. K., Ley, K. & Zernecke, A. & 4 others, Cochain, C., Kemper, C., Mallat, Z. & Binder, C. J., Aug 8 2023, In: Immunity. 56, 8, p. 1809-1824.e10 Research output: Contribution to journal › Article › peer-review
Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes Slysz, J., Sinha, A., DeBerge, M., Singh, S., Avgousti, H., Lee, I., Glinton, K., Nagasaka, R., Dalal, P., Alexandria, S., Wai, C. M., Tellez, R., Vescovo, M., Sunderraj, A., Wang, X., Schipma, M., Sisk, R., Gulati, R., Vallejo, J. & Saigusa, R. & 8 others, Lloyd-Jones, D. M., Lomasney, J., Weinberg, S., Ho, K., Ley, K., Giannarelli, C., Thorp, E. B. & Feinstein, M. J., 2023, In: JCI Insight. 8, 17, e171359. Research output: Contribution to journal › Article › peer-review
Mast cells must stick Lyu, Q., Wang, Y. & Ley, K., Aug 2023, In: Journal of Leukocyte Biology. 114, 2, p. 109-110 2 p. Research output: Contribution to journal › Editorial › peer-review
Author Correction: Human circulating CD24^hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease (Nature Cardiovascular Research, (2023), 2, 11, (1003-1014), 10.1038/s44161-023-00356-1) Pattarabanjird, T., Nguyen, A. T., McSkimming, C., Dinh, H. Q., Marshall, M. A., Ghosheh, Y., Gulati, R., Durant, C., Vallejo, J., Saigusa, R., Drago, F., Guy, T. V., Premo, K., Taylor, A. M., Paul, S., Kundu, B., Berr, S., Gonen, A., Tsimikas, S. & Miller, Y. & 4 others, Pillai, S., Ley, K., Hedrick, C. C. & McNamara, C. A., Dec 2023, In: Nature Cardiovascular Research. 2, 12, p. 1328 1 p. Research output: Contribution to journal › Comment/debate › peer-review
Chemokine Receptor Activation Enhances Memory B Cell Class Switching Linked to IgE Sensitization to Alpha Gal and Cardiovascular Disease Pattarabanjird, T., Wilson, J. M., Erickson, L. D., Workman, L. J., Qiao, H., Ghosheh, Y., Gulati, R., Durant, C., Vallejo, J., Saigusa, R., Platts-Mills, T. A. E., Taylor, A. M., Ley, K. & McNamara, C. A., 2021, In: Frontiers in Cardiovascular Medicine. 8, 791028. Research output: Contribution to journal › Article › peer-review
Autoimmune Regulator (AIRE) Deficiency Does Not Affect Atherosclerosis and CD4 T Cell Immune Tolerance to Apolipoprotein B Nettersheim, F. S., Braumann, S., Kobiyama, K., Orecchioni, M., Vassallo, M., Miller, J., Ali, A., Roy, P., Saigusa, R., Wolf, D., Ley, K. & Winkels, H., 2021, In: Frontiers in Cardiovascular Medicine. 8, 812769. Research output: Contribution to journal › Article › peer-review
Human circulating CD24^hi marginal zone B cells produce IgM targeting atherogenic antigens and confer protection from vascular disease Pattarabanjird, T., Nguyen, A. T., McSkimming, C., Dinh, H. Q., Marshall, M. A., Ghosheh, Y., Gulati, R., Durant, C., Vallejo, J., Saigusa, R., Drago, F., Guy, T. V., Premo, K., Taylor, A. M., Paul, S., Kundu, B., Berr, S., Gonen, A., Tsimikas, S. & Miller, Y. & 4 others, Pillai, S., Ley, K., Hedrick, C. C. & McNamara, C. A., Nov 2023, In: Nature Cardiovascular Research. 2, 11, p. 1003-1014 12 p. Research output: Contribution to journal › Article › peer-review
Identification of human exT_reg cells as CD16⁺CD56⁺ cytotoxic CD4⁺ T cells Freuchet, A., Roy, P., Armstrong, S. S., Oliaeimotlagh, M., Kumar, S., Orecchioni, M., Ali, A. J., Khan, A., Makings, J., Lyu, Q., Winkels, H., Wang, E., Durant, C., Ghosheh, Y., Gulati, R., Nettersheim, F. & Ley, K., Oct 2023, In: Nature Immunology. 24, 10, p. 1748-1761 14 p. Research output: Contribution to journal › Article › peer-review
Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease Saigusa, R., Roy, P., Freuchet, A., Gulati, R., Ghosheh, Y., Armstrong Suthahar, S. S., Durant, C. P., Hanna, D. B., Kiosses, W. B., Orecchioni, M., Wen, L., Wu, R., Kuniholm, M. H., Landay, A. L., Anastos, K., Tien, P. C., Gange, S. J., Kassaye, S., Vallejo, J. & Hedrick, C. C. & 5 others, Kwok, W. W., Sette, A., Hodis, H. N., Kaplan, R. C. & Ley, K., May 2022, In: Nature Cardiovascular Research. 1, 5, p. 462-475 14 p. Research output: Contribution to journal › Article › peer-review
Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis Wang, Z., Zhang, X., Lu, S., Zhang, C., Ma, Z., Su, R., Li, Y., Sun, T., Li, Y., Hong, M., Deng, X., Rafiee Monjezi, M., Hristov, M., Steffens, S., Santovito, D., Dornmair, K., Ley, K., Weber, C., Mohanta, S. K. & Habenicht, A. J. R. & 1 others, Yin, C., Mar 2023, In: Nature Cardiovascular Research. 2, 3, p. 290-306 17 p. Research output: Contribution to journal › Article › peer-review
Integrated single-cell analysis-based classification of vascular mononuclear phagocytes in mouse and human atherosclerosis Zernecke, A., Erhard, F., Weinberger, T., Schulz, C., Ley, K., Saliba, A. E. & Cochain, C., Jun 1 2023, In: Cardiovascular Research. 119, 8, p. 1676-1689 14 p. Research output: Contribution to journal › Article › peer-review
V₄C₃ MXene Immune Profiling and Modulation of T Cell-Dendritic Cell Function and Interaction Fusco, L., Gazzi, A., Shuck, C. E., Orecchioni, M., Ahmed, E. I., Giro, L., Zavan, B., Yilmazer, A., Ley, K., Bedognetti, D., Gogotsi, Y. & Delogu, L. G., Aug 18 2023, In: Small Methods. 7, 8, 2300197. Research output: Contribution to journal › Article › peer-review
HIV infection and cardiovascular disease have both shared and distinct monocyte gene expression features: Women’s Interagency HIV study Lin, J., Ehinger, E., Hanna, D. B., Qi, Q., Wang, T., Ghosheh, Y., Mueller, K., Anastos, K., Lazar, J. M., Mack, W. J., Tien, P. C., Berman, J. W., Cohen, M. H., Ofotokun, I., Gange, S., Liu, C., Heath, S. L., Tracy, R. P., Hodis, H. N. & Landay, A. L. & 2 others, Ley, K. & Kaplan, R. C., May 2023, In: PloS one. 18, 5 May, e0285926. Research output: Contribution to journal › Article › peer-review
How Lymphatic Endothelial Cells Destabilize Regulatory T Cells Lyu, Q. & Ley, K., Feb 1 2023, In: Arteriosclerosis, thrombosis, and vascular biology. 43, 2, p. 215-217 3 p. Research output: Contribution to journal › Editorial › peer-review
Single-cell transcriptomes and T cell receptors of vaccine-expanded apolipoprotein B-specific T cells Nettersheim, F. S., Ghosheh, Y., Winkels, H., Kobiyama, K., Durant, C., Armstrong, S. S., Brunel, S., Roy, P., Dileepan, T., Jenkins, M. K., Zajonc, D. M. & Ley, K., Jan 5 2023, In: Frontiers in Cardiovascular Medicine. 9, 1076808. Research output: Contribution to journal › Article › peer-review
Kindlin2 enables EphB/ephrinB bi-directional signaling to support vascular development Li, W., Wen, L., Rathod, B., Gingras, A. C., Ley, K. & Lee, H. S., Mar 1 2023, In: Life Science Alliance. 6, 3 Research output: Contribution to journal › Article › peer-review
Deleting interleukin-10 from myeloid cells exacerbates atherosclerosis in Apoe ^−/− mice Orecchioni, M., Wolf, D., Suryawanshi, V., Winkels, H., Kobiyama, K., Makings, J., Kiosses, W. B. & Ley, K., Jan 2023, In: Cellular and Molecular Life Sciences. 80, 1, 10. Research output: Contribution to journal › Article › peer-review
Titration of 124 antibodies using CITE-Seq on human PBMCs Nettersheim, F. S., Armstrong, S. S., Durant, C., Blanco-Dominguez, R., Roy, P., Orecchioni, M., Suryawanshi, V. & Ley, K., Dec 2022, In: Scientific reports. 12, 1, 20817. Research output: Contribution to journal › Article › peer-review
Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformation Disease Lai, C. C., Nelsen, B., Frias-Anaya, E., Gallego-Gutierrez, H., Orecchioni, M., Herrera, V., Ortiz, E., Sun, H., Mesarwi, O. A., Ley, K., Gongol, B. & Lopez-Ramirez, M. A., Nov 11 2022, In: Circulation research. 131, 11, p. 909-925 17 p. Research output: Contribution to journal › Article › peer-review
L-selectin: mechanisms and physiological significance of ectodomain cleavage. Smalley, D. M. & Ley, K., 2005, In: Journal of Cellular and Molecular Medicine. 9, 2, p. 255-266 12 p. Research output: Contribution to journal › Review article › peer-review
Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules Buscher, K., Wang, H., Zhang, X., Striewski, P., Wirth, B., Saggu, G., Lütke-Enking, S., Mayadas, T. N., Ley, K., Sorokin, L. & Song, J., Mar 4 2016, In: Nature communications. 7, 10828. Research output: Contribution to journal › Article › peer-review
Therapeutic inhibition of CXCR2 by Reparixin attenuates acute lung injury in mice Zarbock, A., Allegretti, M. & Ley, K., Oct 2008, In: British Journal of Pharmacology. 155, 3, p. 357-364 8 p. Research output: Contribution to journal › Article › peer-review
Effect of oxygen tension on regulation of arteriolar diameter in skeletal muscle in situ Pries, A. R., Heide, J., Ley, K., Klotz, K. F. & Gaehtgens, P., 1995, In: Microvascular Research. 49, 3, p. 289-299 11 p. Research output: Contribution to journal › Article › peer-review
Improved survival and reduced vascular permeability by eliminating or blocking 12/15-lipoxygenase in mouse models of Acute Lung Injury (ALI) Zarbock, A., DiStasi, M. R., Smith, E., Sanders, J. M., Kronke, G., Harry, B. L., Von Vietinghoff, S., Buscher, K., Nadler, J. L. & Ley, K., Oct 1 2009, In: Journal of Immunology. 183, 7, p. 4715-4722 8 p. Research output: Contribution to journal › Article › peer-review
IL-17A inhibits the expansion of IL-17A-producing T cells in mice through "short-loop" inhibition via IL-17 receptor Smith, E., Stark, M. A., Zarbock, A., Burcin, T. L., Bruce, A. C., Vaswani, D., Foley, P. & Ley, K., Jul 15 2008, In: Journal of Immunology. 181, 2, p. 1357-1364 8 p. Research output: Contribution to journal › Article › peer-review
Induction of dendritic cell-like phenotype in macrophages during foam cell formation Hyung, J. C., Shashkin, P., Gleissner, C. A., Dunson, D., Jain, N., Lee, J. K., Miller, Y. & Ley, K., Apr 24 2007, In: Physiological Genomics. 29, 2, p. 149-160 12 p. Research output: Contribution to journal › Article › peer-review
Biomedical application of target tracking in clutter Goobic, A. P., Welser, M. E., Acton, S. T. & Ley, K., 2001, In: Conference Record of the Asilomar Conference on Signals, Systems and Computers. 1, p. 88-92 5 p. Research output: Contribution to journal › Conference article › peer-review
Flow cytometry analysis of immune cells within murine aortas Butcher, M. J., Herre, M., Ley, K. & Galkina, E., Jul 2011, In: Journal of Visualized Experiments. 53, e2848. Research output: Contribution to journal › Article › peer-review
Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery Ley, K., Linnemann, G., Meinen, M., Stoolman, L. M. & Gaehtgens, P., Jan 1 1993, In: Blood. 81, 1, p. 177-185 9 p. Research output: Contribution to journal › Article › peer-review
Identification of novel downstream targets of platelet glycoprotein VI activation by differential proteome analysis: Implications for thrombus formation Schulz, C., Leuschen, N. V., Fröhlich, T., Lorenz, M., Pfeiler, S., Gleissner, C. A., Kremmer, E., Kessler, M., Khandoga, A. G., Engelmann, B., Ley, K., Massberg, S. & Arnold, G. J., May 20 2010, In: Blood. 115, 20, p. 4102-4110 9 p. Research output: Contribution to journal › Article › peer-review
CXCR6 promotes atherosclerosis by supporting T-cell homing, interferon-γ production, and macrophage accumulation in the aortic wall Galkina, E., Harry, B. L., Ludwig, A., Liehn, E. A., Sanders, J. M., Bruce, A., Weber, C. & Ley, K., Oct 2007, In: Circulation. 116, 16, p. 1801-1811 11 p. Research output: Contribution to journal › Article › peer-review
MISTICA: Minimum Spanning Tree-Based Coarse Image Alignment for Microscopy Image Sequences Ray, N., McArdle, S., Ley, K. & Acton, S. T., Nov 2016, In: IEEE Journal of Biomedical and Health Informatics. 20, 6, p. 1575-1584 10 p. Research output: Contribution to journal › Article › peer-review
Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice Meng, F., Wang, K., Aoyama, T., Grivennikov, S. I., Paik, Y., Scholten, D., Cong, M., Iwaisako, K., Liu, X., Zhang, M., Sterreicher, C. H., Stickel, F., Ley, K., Brenner, D. A. & Kisseleva, T., Sep 2012, In: Gastroenterology. 143, 3, p. 765-776.e3 Research output: Contribution to journal › Article › peer-review
The trafficking protein JFC1 regulates Rac1-GTP localization at the uropod controlling neutrophil chemotaxis and in vivo migration Ramadass, M., Johnson, J. L., Marki, A., Zhang, J., Wolf, D., Kiosses, W. B., Pestonjamasp, K., Ley, K. & Catz, S. D., Jun 2019, In: Journal of Leukocyte Biology. 105, 6, p. 1209-1224 16 p. Research output: Contribution to journal › Article › peer-review
Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720 Kharel, Y., Lee, S., Snyder, A. H., Sheasley-O'Neill, S. L., Morris, M. A., Setiady, Y., Zhu, R., Zigler, M. A., Burcin, T. L., Ley, K., Tung, K. S. K., Engelhard, V. H., Macdonald, T. L., Pearson-White, S. & Lynch, K. R., Nov 4 2005, In: Journal of Biological Chemistry. 280, 44, p. 36865-36872 8 p. Research output: Contribution to journal › Article › peer-review
CXC chemokine ligand 4 induces a unique transcriptome in monocyte-derived macrophages Gleissner, C. A., Shaked, I., Little, K. M. & Ley, K., May 1 2010, In: Journal of Immunology. 184, 9, p. 4810-4818 9 p. Research output: Contribution to journal › Article › peer-review
Sialyltransferase specificity in selectin ligand formation Ellies, L. G., Sperandio, M., Underhill, G. H., Yousif, J., Smith, M., Priatel, J. J., Kansas, G. S., Ley, K. & Marth, J. D., Nov 15 2002, In: Blood. 100, 10, p. 3618-3625 8 p. Research output: Contribution to journal › Article › peer-review
Editorial: Tyrosine sulfation of leukocyte adhesion molecules and chemokine receptors promotes atherosclerosis Koltsova, E. & Ley, K., Nov 2009, In: Arteriosclerosis, thrombosis, and vascular biology. 29, 11, p. 1709-1711 3 p. Research output: Contribution to journal › Editorial › peer-review

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