Community Academic Profiles - Faculty & Researchers

All Publications

B Cells, T Cells and Inflammatory CSF Biomarkers in Primary Progressive MS and Relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Trial Bar-Or, A., Bennett, J., Von Budingen, H., Carruthers, R., Edwards, K., Fallis, R., Fiore, D., Gelfand, J., Giacomini, P., Greenberg, B., Hafler, D., Longbrake, E., Assman, B., Ionete, C., Kaunzner, U., Lock, C., Ma, X., Musch, B., Pardo, G., Pei, J., Piehl, F., Weber, M., Ziemssen, T., Herman, A., Harp, C., Cross, A. LIPPINCOTT WILLIAMS & WILKINS. 2020
View details for Web of Science ID 000536058003079
Ocrelizumab treatment reduced levels of neurofilament light chain and numbers of B cells in the cerebrospinal fluid of patients with relapsing multiple sclerosis in the OBOE study Cross, A., Bennett, J., von Budingen, H., Carruthers, R., Edwards, K., Fallis, R., Fiore, D., Gelfand, J., Giacomini, P., Greenberg, B., Hafler, D., Harp, C., Assman, B., Herman, A., Ionete, C., Kaunzner, U., Lock, C., Ma, X., Musch, B., Pardo, G., Piehl, F., Weber, M., Ziemssen, T., Bar-Or, A. LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965907093
MR susceptibility contrast imaging using a 2D simultaneous multi-slice gradient-echo sequence at 7T. PloS one Bian, W., Kerr, A. B., Tranvinh, E., Parivash, S., Zahneisen, B., Han, M. H., Lock, C. B., Goubran, M., Zhu, K., Rutt, B. K., Zeineh, M. M. 2019; 14 (7): e0219705
Abstract

PURPOSE: To develop a 7T simultaneous multi-slice (SMS) 2D gradient-echo sequence for susceptibility contrast imaging, and to compare its quality to 3D imaging.METHODS: A frequency modulated and phase cycled RF pulse was designed to simultaneously excite multiple slices in multi-echo 2D gradient-echo imaging. The imaging parameters were chosen to generate images with susceptibility contrast, including T2*-weighted magnitude/phase images, susceptibility-weighted images and quantitative susceptibility/R2* maps. To compare their image quality with 3D gradient-echo imaging, both 2D and 3D imaging were performed on 11 healthy volunteers and 4 patients with multiple sclerosis (MS). The signal to noise ratio (SNR) in gray and white matter and their contrast to noise ratio (CNR) was simulated for the 2D and 3D magnitude images using parameters from the imaging. The experimental SNRs and CNRs were measured in gray/white matter and deep gray matter structures on magnitude, phase, R2* and QSM images from volunteers and the visibility of MS lesions on these images from patients was visually rated. All SNRs and CNRs were compared between the 2D and 3D imaging using a paired t-test.RESULTS: Although the 3D magnitude images still had significantly higher SNRs (by 13.0~17.6%), the 2D magnitude and QSM images generated significantly higher gray/white matter or globus pallidus/putamen contrast (by 13.3~87.5%) and significantly higher MS lesion contrast (by 5.9~17.3%).CONCLUSION: 2D SMS gradient-echo imaging can serve as an alternative to often used 3D imaging to obtain susceptibility-contrast-weighted images, with an advantage of providing better image contrast and MS lesion sensitivity.

View details for DOI 10.1371/journal.pone.0219705

View details for PubMedID 31314813
Autoimmune Hepatitis During Treatment of Multiple Sclerosis with Alemtuzumab Carlson, A., Bozinov, N., Kipp, L., Dunn, J., Lock, C. LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000453090804181
A Multi-scale Multiple Sclerosis Lesion Change Detection in a Multi-sequence MRI Cheng, M., Galimzianova, A., Lesjak, Z., Spiclin, Z., Lock, C. B., Rubin, D. L., Stoyanov, D., Taylor, Z., Carneiro, G., SyedaMahmood, T. SPRINGER INTERNATIONAL PUBLISHING AG. 2018: 353?60
View details for DOI 10.1007/978-3-030-00889-5_40

View details for Web of Science ID 000477761800040
Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice JOURNAL OF EXPERIMENTAL MEDICINE Han, M. H., Lundgren, D. H., Jaiswal, S., Chao, M., Graham, K. L., Garris, C. S., Axtell, R. C., Ho, P. P., Lock, C. B., Woodard, J. I., Brownell, S. E., Zoudilova, M., Hunt, J. F., Baranzini, S. E., Butcher, E. C., Raine, C. S., Sobel, R. A., Han, D. K., Weissman, I., Steinman, L. 2012; 209 (7): 1325-1334
Abstract

Comparison of transcriptomic and proteomic data from pathologically similar multiple sclerosis (MS) lesions reveals down-regulation of CD47 at the messenger RNA level and low abundance at the protein level. Immunohistochemical studies demonstrate that CD47 is expressed in normal myelin and in foamy macrophages and reactive astrocytes within active MS lesions. We demonstrate that CD47(-/-) mice are refractory to experimental autoimmune encephalomyelitis (EAE), primarily as the result of failure of immune cell activation after immunization with myelin antigen. In contrast, blocking with a monoclonal antibody against CD47 in mice at the peak of paralysis worsens EAE severity and enhances immune activation in the peripheral immune system. In vitro assays demonstrate that blocking CD47 also promotes phagocytosis of myelin and that this effect is dependent on signal regulatory protein ? (SIRP-?). Immune regulation and phagocytosis are mechanisms for CD47 signaling in autoimmune neuroinflammation. Depending on the cell type, location, and disease stage, CD47 has Janus-like roles, with opposing effects on EAE pathogenesis.

View details for DOI 10.1084/jem.20101974

View details for Web of Science ID 000306174300008

View details for PubMedID 22734047

View details for PubMedCentralID PMC3405500
Inhibitory role for GABA in autoimmune inflammation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Bhat, R., Axtell, R., Mitra, A., Miranda, M., Lock, C., Tsien, R. W., Steinman, L. 2010; 107 (6): 2580-2585
Abstract

GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.

View details for DOI 10.1073/pnas.0915139107

View details for Web of Science ID 000274408100041

View details for PubMedID 20133656

View details for PubMedCentralID PMC2823917
Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis NATURE MEDICINE Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., Langer-Gould, A., Strober, S., Cannella, B., Allard, J., Klonowski, P., Austin, A., Lad, N., Kaminski, N., GALLI, S. J., Oksenberg, J. R., Raine, C. S., Heller, R., Steinman, L. 2002; 8 (5): 500-508
Abstract

Microarray analysis of multiple sclerosis (MS) lesions obtained at autopsy revealed increased transcripts of genes encoding inflammatory cytokines, particularly interleukin-6 and -17, interferon-gamma and associated downstream pathways. Comparison of two poles of MS pathology--acute lesions with inflammation versus 'silent' lesions without inflammation--revealed differentially transcribed genes. Some products of these genes were chosen as targets for therapy of experimental autoimmune encephalomyelitis (EAE) in mice. Granulocyte colony-stimulating factor is upregulated in acute, but not in chronic, MS lesions, and the effect on ameliorating EAE is more pronounced in the acute phase, in contrast to knocking out the immunoglobulin Fc receptor common gamma chain where the effect is greatest on chronic disease. These results in EAE corroborate the microarray studies on MS lesions. Large-scale analysis of transcripts in MS lesions elucidates new aspects of pathology and opens possibilities for therapy.

View details for DOI 10.1038/nm0502-500

View details for PubMedID 11984595
The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease SCIENCE Chabas, D., Baranzini, S. E., Mitchell, D., Bernard, C. C., Rittling, S. R., Denhardt, D. T., Sobel, R. A., Lock, C., Karpuj, M., Pedotti, R., Heller, R., Oksenberg, J. R., Steinman, L. 2001; 294 (5547): 1731-1735
Abstract

Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (OPN). Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, also revealed increased OPN transcripts. Osteopontin-deficient mice were resistant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamma than in OPN+/+ mice. Osteopontin thus appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.

View details for Web of Science ID 000172307400049

View details for PubMedID 11721059
The role of TNF alpha and lymphotoxin in demyelinating disease ANNALS OF THE RHEUMATIC DISEASES Lock, C., Oksenberg, J., Steinman, L. 1999; 58: 121-128
View details for Web of Science ID 000084239700023
The role of TNFalpha and lymphotoxin in demyelinating disease. Annals of the rheumatic diseases Lock, C., Oksenberg, J., Steinman, L. 1999; 58: I121-8
View details for PubMedID 10577988
EXPRESSION OF HLA-DR4 AND HUMAN CD4 TRANSGENES IN MICE DETERMINES THE VARIABLE REGION BETA-CHAIN T-CELL REPERTOIRE AND MEDIATES AN HLA-DR-RESTRICTED IMMUNE-RESPONSE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Fugger, L., Michie, S. A., Rulifson, I., Lock, C. B., McDevitt, G. S. 1994; 91 (13): 6151-6155
Abstract

Inherited susceptibility to rheumatoid arthritis is associated with genes encoding the human major histocompatibility complex class II molecule HLA-DR4. To study the immune function of HLA-DR4 and attempt to generate a murine model of rheumatoid arthritis we have produced triple transgenic mice expressing HLA-DRA*0101, -DRB1*0401, and human CD4. The expression of the HLA transgenes is driven by the promoter of the murine major histocompatibility complex class II I-E alpha gene and was found on murine cells that normally display major histocompatibility complex class II molecules. The expression of the human CD4 transgene is driven by the murine CD3 delta-promoter, and therefore its gene product was found on cells that express murine CD3. In contrast to other HLA-DR and HLA-DQ transgenic mouse lines, the transgenes are functional in our mice. In H-2 I-E-negative transgenic mice, T cells expressing variable region beta chain (V beta) 3, 5, 6, 7, 9, 11, 12, or 13 were either absent or significantly reduced, in contrast to H-2 I-E-negative nontransgenic littermates. In addition, the peptide antigen influenza A virus hemagglutinin 307-319, which binds to the HLA-DRA*0101/-DRB1*0401 heterodimer with high affinity and induces an HLA-DR-restricted and CD4+ T-cell response in humans, also induced a T-cell response in the triple transgenic mice but not in nontransgenic littermates. Thus, these transgenic mice should permit extensive testing of the antigen-presentation capabilities of the HLA-DRA*0101/-DRB1*0401 molecule.

View details for Web of Science ID A1994NT46100086

View details for PubMedID 8016129
MINIMUM STRUCTURAL REQUIREMENTS FOR PEPTIDE PRESENTATION BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES - IMPLICATIONS IN INDUCTION OF AUTOIMMUNITY PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Gautam, A. M., Lock, C. B., Smilek, D. E., Pearson, C. I., Steinman, L., McDevitt, H. O. 1994; 91 (2): 767-771
Abstract

The precise mechanisms of failure of immunological tolerance to self proteins are not known. Major histocompatibility complex (MHC) susceptibility alleles, the target peptides, and T cells with anti-self reactivity must be present to cause autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a murine model of a human autoimmune disease, multiple sclerosis. In EAE, residues 1-11 of myelin basic protein (MBP) are the dominant disease-inducing determinants in PL/J and (PL/J x SJL/J)F1 mice. Here we report that a six-residue peptide (five of them native) of MBP can induce EAE. Using peptide analogues of the MBP-(1-11) peptide, we demonstrate that only four native MBP residues are required to stimulate MBP-specific T cells. Therefore, this study demonstrates lower minimum structural requirements for effective antigen presentation by MHC class II molecules. Many viral and bacterial proteins share short runs of amino acid similarity with host self proteins, a phenomenon known as molecular mimicry. Since a six-residue peptide can sensitize MBP-specific T cells to cause EAE, these results define a minimum sequence identity for molecular mimicry in autoimmunity.

View details for Web of Science ID A1994MR98900070

View details for PubMedID 7507253
ANTIGEN RECOGNITION AND PEPTIDE-MEDIATED IMMUNOTHERAPY IN AUTOIMMUNE-DISEASE IMMUNOLOGICAL REVIEWS Smilek, D. E., Lock, C. B., McDevitt, H. O. 1990; 118: 37-71
View details for Web of Science ID A1990EU70000003

View details for PubMedID 1706681

COVID-19 Updates

Stanford Medicine is closely monitoring the outbreak of novel coronavirus (COVID-19). A new page is dedicated to the latest information and developments about COVID-19.

Follow Stanford Medicine

��

Health Care

Healing through compassion and world-class science

Research

Fueling discovery and innovation to advance human health

Education

Empowering tomorrow's leading physicians and scientists

Faculty

Students

Community

RACIAL JUSTICE

Our Pledge

Racism and discrimination are direct affronts to Stanford Medicine?s values. Read our leaders? pledge on racial equity.

About
Stanford Medicine

A leader in the biomedical revolution, Stanford Medicine has a long tradition of leadership in pioneering research, creative teaching protocols and effective clinical therapies.

Study of COVID-19 saliva test

An at-home COVID-19 test, designed by Stanford researchers to be easy to use and provide results within 30 minutes, will be the focus of a study funded by the Stanford Medicine Catalyst Program.

covid-19 research at Stanford Medicine

Our scientists have launched dozens of research projects as part of the global response to COVID-19. Some aim to prevent, diagnose and treat the disease; others aim to understand how it spreads and how people?s immune systems respond to it.

community

Christopher Lock

Clinical Associate Professor, Neurology & Neurological Sciences

Bio

Clinical Focus

Academic Appointments

Administrative Appointments

Boards, Advisory Committees, Professional Organizations

Professional Education

Contact

Links

Research & Scholarship

Clinical Trials

Publications

All Publications

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Find a doctor

Clinics & Services

Research Resources

Professional Training

Education Resources

COVID-19 Updates

Follow Stanford Medicine

Health Care

Research

Education

Our Pledge

About
Stanford Medicine

Study of COVID-19 saliva test

Letter to our Stanford Medicine community

How to bounce back from the pandemic

Breaking COVID-19's deadly embrace

Site Navigation:

Footer Links:

Stanford Medicine Resources:

Christopher Lock

Clinical Associate Professor, Neurology & Neurological Sciences

Bio

Clinical Focus

Academic Appointments

Administrative Appointments

Boards, Advisory Committees, Professional Organizations

Professional Education

Contact

Links

Research & Scholarship

Clinical Trials

Publications

All Publications

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

You are Here:

Current Tab: 6

COVID-19 Updates

Follow Stanford Medicine

Health Care

Research

Education

Our Pledge

AboutStanford Medicine

Study of COVID-19 saliva test

Letter to our Stanford Medicine community

How to bounce back from the pandemic

Breaking COVID-19's deadly embrace

Site Navigation:

Footer Links:

Stanford Medicine Resources:

About
Stanford Medicine