Cleveland Clinic Lerner Research Institute

Cleveland, OH, United States

Cleveland Clinic Lerner Research Institute

Cleveland, OH, United States

The Cleveland Clinic Lerner Research Institute is home to all laboratory-based, translational and clinical research at the Cleveland Clinic.The Institute comprises 11 Departments: Biomedical Engineering, Cancer Biology, Cell Biology, Genomic Medicine Institute, Immunology, Molecular Cardiology, Molecular Genetics , Neuroscience, Pathobiology, Quantitative Health science, and Stem Cell Biology and Regenerative Medicine.More than 1,300 work at the Institute, including about 200 Principal Investigators who have laboratory space. Its Staff members also participate in the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and the Molecular Medicine PhD Program. In 2008, the Institute had a total research budget of $258 million . More than 260 Postdoctoral Fellows and 170 Graduate Students continued their professional development. Research by the Staff appeared in nearly 1,300 journal manuscripts, books or book chapters. The Institute's Chair is Paul E. DiCorleto, PhD, who was named to the position in 2002. He is the fifth Chair since the Institute was founded in 1945. Wikipedia.

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Prinz M.,University Hospital Freiburg | Priller J.,Charité - Medical University of Berlin | Sisodia S.S.,University of Chicago | Ransohoff R.M.,Cleveland Clinic Lerner Research Institute
Nature Neuroscience | Year: 2011

The diseased brain hosts a heterogeneous population of myeloid cells, including parenchymal microglia, perivascular cells, meningeal macrophages and blood-borne monocytes. To date, the different types of brain myeloid cells have been discriminated solely on the basis of their localization, morphology and surface epitope expression. However, recent data suggest that resident microglia may be functionally distinct from bone marrow-or blood-derived phagocytes, which invade the CNS under pathological conditions. During the last few years, research on brain myeloid cells has been markedly changed by the advent of new tools in imaging, genetics and immunology. These methodologies have yielded unexpected results, which challenge the traditional view of brain macrophages. On the basis of these new studies, we differentiate brain myeloid subtypes with regard to their origin, function and fate in the brain and illustrate the divergent features of these cells during neurodegeneration. © 2011 Nature America, Inc. All rights reserved.


Temel R.E.,University of Kentucky | Brown J.M.,Cleveland Clinic Lerner Research Institute
Trends in Pharmacological Sciences | Year: 2015

Cardiovascular disease (CVD) remains the largest cause of mortality in most developed countries. Although recent failed clinical trials and Mendelian randomization studies have called into question the high-density lipoprotein (HDL) hypothesis, it remains well accepted that stimulating the process of reverse cholesterol transport (RCT) can prevent or even regress atherosclerosis. The prevailing model for RCT is that cholesterol from the artery wall must be delivered to the liver where it is secreted into bile before leaving the body through fecal excretion. However, many studies have demonstrated that RCT can proceed through a non-biliary pathway known as transintestinal cholesterol excretion (TICE). The goal of this review is to discuss the current state of knowledge of the TICE pathway, with emphasis on points of therapeutic intervention. © 2015 Elsevier Ltd. All rights reserved.


Hine C.,Cleveland Clinic Lerner Research Institute
Science Translational Medicine | Year: 2017

Two weeks of rapamycin administration in young and old female mice leads to long-term improvements in ovarian function and reproductive longevity. © 2017, American Association for the Advancement of Science.


Hine C.,Cleveland Clinic Lerner Research Institute
Science Translational Medicine | Year: 2017

Vaccination with potato virus X nanoparticles enhances the efficacy of traditional doxorubicin anticancer therapy against a mouse melanoma tumor model. ©2017, American Association for the Advancement of Science.


Obermeier B.,Cleveland Clinic Lerner Research Institute | Daneman R.,University of California at San Francisco | Ransohoff R.M.,Cleveland Clinic Lerner Research Institute
Nature Medicine | Year: 2013

The interface between the blood circulation and the neural tissue features unique characteristics that are encompassed by the term 'blood-brain barrier' (BBB). The main functions of this barrier, namely maintenance of brain homeostasis, regulation of influx and efflux transport, and protection from harm, are determined by its specialized multicellular structure. Every constituent cell type makes an indispensable contribution to the BBB's integrity. But if one member of the BBB fails, and as a result the barrier breaks down, there can be dramatic consequences and neuroinflammation and neurodegeneration can occur. In this Review, we highlight recently gained mechanistic insights into the development and maintenance of the BBB. We then discuss how BBB disruption can cause or contribute to neurological disease. Finally, we examine how this knowledge can be used to explore new possibilities for BBB repair. © 2013 Nature America, Inc.


Sossey-Alaoui K.,Cleveland Clinic Lerner Research Institute
Seminars in Cell and Developmental Biology | Year: 2013

WAVE3 belongs to the WASP/WAVE family of actin cytoskeleton remodeling proteins. These proteins are known to be involved in several biological functions ranging from controlling cell shape and movement, to being closely associated with pathological conditions such as cancer progression and metastasis. Last decade has seen an explosion in the literature reporting significant scientific advances on the molecular mechanisms whereby the WASP/WAVE proteins are regulated both in normal physiological as well as pathological conditions. The purpose of this review is to present the major findings pertaining to how WAVE3 has become a critical player in the regulation of signaling pathways involved in cancer progression and metastasis. The review will conclude with suggesting options for the potential use of WAVE3 as a therapeutic target to prevent the progression of cancer to the lethal stage that is the metastatic disease. © 2012 Elsevier Ltd.


de la Motte C.A.,Cleveland Clinic Lerner Research Institute
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011

The causes of fibrosis, or the inappropriate wound healing, that follows chronic intestinal inflammation are not well defined and likely involve the contributions of multiple cellular mechanisms. As other articles in this series confirm, inflammatory cytokines clearly play a role in driving cell differentiation to the myofibroblast phenotype, promoting proliferation and extracellular matrix deposition that are characteristic of fibrotic tissue. However, controlling the balance of cytokines produced and process of myofibroblast differentiation appears to be more complex. This review considers ways in which hyaluronan, an extracellular matrix component that is remodeled during the progression of colitis, may provide indirect as well as direct cues that influence the balancing act of intestinal wound healing. © 2011 by the American Physiological Society.


McIntyre T.M.,Cleveland Clinic Lerner Research Institute
Biochimica et Biophysica Acta - Biomembranes | Year: 2012

This report reviews structurally related phospholipid oxidation products that are biologically active where molecular mechanisms have been defined. Phospholipids containing polyunsaturated fatty acyl residues are chemically or enzymatically oxidized to phospholipid hydroperoxides, which may fragment on either side of the newly introduced peroxy function to form phospholipids with a truncated sn-2 residue. These truncated phospholipids not subject to biologic control of their production and, depending on the sn-2 residue length and structure, can stimulate the plasma membrane receptor for PAF. Alternatively, these chemically formed products can be internalized by a transport system to either stimulate the lipid activated nuclear transcription factor PPARγ or at higher levels interact with mitochondria to initiate the intrinsic apoptotic cascade. Intracellular PAF acetylhydrolases specifically hydrolyze truncated phospholipids, and not undamaged, biosynthetic phospholipids, to protect cells from oxidative death. Truncated phospholipids are also formed within cells where they couple cytokine stimulation to mitochondrial damage and apoptosis. The relevance of intracellular truncated phospholipids is shown by the complete protection from cytokine induced apoptosis by PAF acetylhydrolase expression. This protection shows truncated phospholipids are the actual effectors of cytokine mediated toxicity. This article is part of a Special Issue entitled: Oxidized phospholipids - their properties and interactions with proteins. © 2011 Elsevier B.V. All rights reserved.


Bhattaram P.,Cleveland Clinic Lerner Research Institute
Nature communications | Year: 2010

During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal and lineage decisions are incompletely understood. In this study, we show that their survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 and Sox12. The more SoxC alleles that are deleted in mouse embryos, the more severe and widespread organ hypoplasia is. SoxC triple-null embryos die at midgestation unturned and tiny, with normal patterning and lineage specification, but with massively dying neural and mesenchymal progenitor cells. Specific inactivation of SoxC genes in neural and mesenchymal cells leads to selective apoptosis of these cells, suggesting SoxC cell-autonomous roles. Tead2 functionally interacts with SoxC genes in embryonic development, and is a direct target of SoxC proteins. SoxC genes therefore ensure neural and mesenchymal progenitor cell survival, and function in part by activating this transcriptional mediator of the Hippo signalling pathway.


Ransohoff R.M.,Cleveland Clinic Lerner Research Institute | Cardona A.E.,Cleveland Clinic Lerner Research Institute
Nature | Year: 2010

A microglial cell is both a glial cell of the central nervous system and a mononuclear phagocyte, which belongs to the haematopoietic system and is involved in inflammatory and immune responses. As such, microglia face a challenging task. The neurons of the central nervous system cannot divide and be replenished, and therefore need to be protected against pathogens, which is a key role of the immune system, but without collateral damage. In addition, after physical injury, neural cells need restorative support, which is provided by inflammatory responses. Excessive or chronic inflammatory responses can, however, be harmful. How microglia balance these demands, and how their behaviour can be modified to ameliorate disorders of the central nervous system, is becoming clear. © 2010 Macmillan Publishers Limited. All rights reserved.

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