Aksam Merched

Aksam Merched
University of Bordeaux · College of Health Sciences

Ph.D, HDR

About

54
Publications
13,656
Reads
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2,245
Citations
Introduction
My research projects are aiming at understanding the interplay between liver metabolic defects, the resolution of inflammation and immunosuppression in the context of liver oncogenesis.
Additional affiliations
July 2016 - present
French Institute of Health and Medical Research
Position
  • Co-leader of the MIRCADE Team
September 2013 - June 2016
French Institute of Health and Medical Research
Position
  • Professor (Full)
Description
  • PI
August 2004 - August 2013
Baylor College of Medicine
Position
  • Professor (Assistant)

Publications

Publications (54)
Article
Full-text available
Atherosclerosis is now recognized as an inflammatory disease involving the vascular wall. Recent results indicate that acute inflammation does not simply passively resolve as previously assumed but is actively terminated by a homeostatic process that is governed by specific lipid-derived mediators initiated by lipoxygenases. Experiments with animal...
Article
The tumor suppressor p53 protects against atherosclerosis progression in several different mouse models. A major target of p53 is p21, the cyclin-dependent kinase inhibitor that regulates entry into the cell cycle of different types of cells, including stem cells. p21 is also involved in the maturation and differentiation of monocytes into macropha...
Article
Higher cardiovascular morbidity in patients with a wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. Our purpose was to investigate the mechanisms of accelerated atherosclerosis and identified vascular autoantigens targeted by autoimmunity. We created a mouse model of autoimmunity-associated a...
Article
Full-text available
Cancer cells are highly dependent on different metabolic pathways to sustain their survival, growth and proliferation. Lipid metabolism supplies not only energetic needs of the cells but also provides the raw material for cellular growth and the signalling molecules for many oncogenic pathways. Mainly processed in the liver, lipids play an essentia...
Article
HMG-CoA reductase inhibitors (known as statins) are commonly prescribed worldwide for the management of coronary heart disease and the underlying dyslipidemia. This class of drugs has been shown to infer significant decrease in the risk of cardiovascular morbidity and mortality. Only recently though, the potentially beneficial effects of statins in...
Article
Full-text available
Metabolic rewiring in tumor cells is a major hallmark of oncogenesis. Some of the oncometabolites drive suppressive and tolerogenic signals from the immune system, which becomes complicit to the advent and the survival of neoplasia. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions acros...
Cover Page
Full-text available
Dear colleagues, Altered cellular metabolism and immunosuppression in the tumor microenvironment became emerging hallmarks of cancer. Oncometabolites are needed to sustain tumor cell survival, growth, and proliferation by fulfilling the energetic needs and providing the raw materials and signaling molecules for many oncogenic pathways. Some are ca...
Chapter
Full-text available
Abstract Background: Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8+CD25+ Treg cells and the impact of microRNAs on molecules associated with immune regulation. Methods: We purified human natural...
Book
Full-text available
Background: MicroRNAs (miRNAs) are small (19-22-nt) single-stranded noncoding RNA molecules whose deregulation of expression can contribute to human disease including the multistep processes of carcinogenesis in human. Circulating miRNAsare emerging biomarkers in many diseases and cancers such as type 2 diabetes, pulmonary disease, colorectal cance...
Article
Full-text available
Hepatoblastoma (HBL) is a pediatric liver cancer with defined molecular alterations driving its progression. Here, we describe an animal model for HBL on the chick chorioallantoic membrane (CAM), which recapitulates relevant features of HBL in patients. Expression of classic tumor-associated proteins such as β-catenin, EpCAM and CK19 was maintained...
Conference Paper
Full-text available
Higher cardiovascular morbidity in patients with wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. The present study was designed to evaluate the autoimmune component of atherogenesis and identify putative antigens that may trigger the autoimmune reactions. We created a mouse model of autoimmu...
Article
The therapeutic hypothesis proposed by Speeckaert and van Geel in this issue (1) is based on the dramatic effect of the new drugs targeting immune privilege checkpoints (PD1/PD-L1, CTLA4) in current advanced melanoma therapy as major inducers of vitiligo-like skin changes. Such striking clinical manifestations cannot be classified as mere adverse e...
Chapter
Full-text available
The integration of the human genome project with nutritional, genetic research, and health outcomes studies has led to the emergence of nutrigenetics and nutrigenomics. These disciplines investigate in a systematic fashion the effect of genetic makeup on individual dietary response and the role of dietary factors and bioactive nutrient products in...
Article
Full-text available
Recruitment of mural cells (MCs), namely pericytes and smooth muscle cells (SMCs), is essential to improve the maturation of newly formed vessels. Sonic hedgehog (Shh) has been suggested to promote the formation of larger and more muscularized vessels, but the underlying mechanisms of this process have not yet been elucidated. We first identified S...
Article
Full-text available
Chronic inflammatory state is linked to the emergence of hepatocellular carcinoma, one of the most common and aggressive cancers worldwide. The complex microenvironment of tumor changes dynamically and consequently affects the pathological process. Understanding the immunological milieu of tumor in hepatocellular carcinoma can have crucial repercus...
Article
Full-text available
The latest genome-wide association studies (GWAS) have re-energized our effort to understand the genetic basis of atherosclerotic cardiovascular disease. Although the knowledge generated by GWAS has confirmed that mediators of inflammation and perturbed lipid metabolism are major players in cardiovascular disease (CVD) development, much of individu...
Article
Full-text available
Pro-resolving and anti-inflammatory mediator products of murine 12/15-lipoxygenase (LOX) exhibit potent actions on vascular inflammation and protect against the progression of atherosclerosis. The present study was designed to determine whether augmenting dietary lipids modulates the body's endogenous anti-inflammatory pro-resolving mechanisms and...
Article
Full-text available
Beta2 integrin-mediated adhesion is thought to be a key event in cardiovascular disease. However, results of clinical trials targeting these molecules have been disappointing. Here, we investigated the effect of inactivation of beta2 integrins at different stages of atherosclerosis by timed bone marrow transplantation (BMT) of CD18(-/-) cells in lo...
Article
Full-text available
To determine the mechanisms involved in regulating the balance between apoptosis and survival in vascular smooth muscle cells (VSMC), we studied anti-apoptotic stimuli that can counteract pro-apoptotic events in the process of early atherosclerotic lesions formation. Such a process involves VSMC accumulation even in the presence of oxidized low den...
Article
We investigated the molecular mechanism of nicotine-accelerated atherosclerosis in a hyperlipidemic low-density lipoprotein receptor(-/-) mouse model. Low-density lipoprotein receptor(-/-) mice received time-release nicotine or placebo pellets for 90 days. Aortic lesion size was 2.5 times larger in nicotine-treated than in placebo-treated mice (P<0...
Article
Full-text available
We tested the efficacy of low-density lipoprotein receptor (LDLR) therapy using helper-dependent adenovirus (HD-Ad), comparing it with that of very low-density lipoprotein receptor (VLDLR), an LDLR homolog. We treated high cholesterol diet fed LDLR-/- mice with a single intravenous injection of HD-Ad expressing monkey LDLR (1.5 x 10(13) or 5 x 10(1...
Article
Full-text available
PGs and leukotrienes (LTs) mediate cardinal signs of inflammation; hence, their enzymes are targets of current anti-inflammatory therapies. Products of arachidonate 15-lipoxygenases (LO) types I and II display both beneficial roles, such as lipoxins (LXs) that stereoselectively signal counterregulation, as well as potential deleterious actions (i.e...
Article
We first showed that absence of p53 accelerates atherosclerosis development in apoE-deficient mice. In this study, we investigated how macrophage-specific loss of p53 function might modulate atherosclerosis development in LDL receptor-deficient mice, a model for familial hypercholesterolemia. We transferred bone marrow cells isolated from p53+/+ an...
Article
Epidemiologic studies and transgenic mouse experiments indicate that high plasma HDL and apolipoprotein (apo) A-I protect against atherosclerosis. We used helper-dependent adenovirus (HD-Ad) gene transfer to examine the effect of long-term hepatic apoA-I expression on atherosclerotic lesion progression and remodeling in a mouse model of familial hy...
Article
Familial hypercholesterolemia (FH) that results from LDL receptor (LDLR) deficiency affects approximately 1 in 500 persons in the heterozygous state and approximately 1 in 1 million persons in the homozygous state. We tested a novel gene therapy strategy for the treatment of FH in a mouse model. We delivered the VLDL receptor (VLDLR) to the liver o...
Article
Full-text available
As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, al...
Article
Slow refolding of human apolipoprotein E (apoE) in solution after guanidine- or cholate-induced denaturation followed by dialysis under controlled conditions was investigated using various spectroscopic properties of fluorescein- and dansyl-labeled apolipoprotein molecules. The results suggest that the last phase(s) of apoE refolding in solution in...
Article
Very low (VLDL) and low density lipoproteins (LDL) were isolated from plasma of patients with the E3/3 phenotype which were divided into three groups based on their plasma triglyceride content: low (TG<200 mg/dl, TG(l)), intermediate (200<300 mg/dl, TG(i)300 mg/dl, TG(h)). The protein density (PD) on the VLDL and LDL surface was calculated from lip...
Article
Serum apolipoprotein (apo) AI concentration was studied in 98 Alzheimer's disease (AD) patients (77.56+/-8.83 years) and 59 healthy, elderly controls (75.37+/-5.27 years). ApoAI levels were significantly lower (p<10(-7)) in AD patients. An apoAI cutoff value of 1.50 g/L, could distinguish between the two groups with a sensitivity of 71% and a speci...
Article
Apolipoprotein D (apoD) is a member of the lipocalin family of proteins. Most members of this family are transporters of small hydrophobic ligands, although in the case of apoD, neither its physiological function(s) nor its putative ligand(s) have been unequivocally identified. In humans, apoD is expressed in several tissues, including the CNS, and...
Article
We measured the levels of two beta-amyloid (Abeta)-sequestering proteins, apolipoprotein (Apo) E and transthyretin (TTR), in ventricular human cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients and controls in relation to brain histological findings. We also studied actin levels in CSF as a marker of the biochemical role of these two pr...
Thesis
Full-text available
La maladie d'Alzheimer (MA) est un problème de santé majeur dans une société qui vieillit de plus en plus. Malgré les progrès importants dans ce domaine, il subsiste beaucoup d'inconnus au niveau physiopathologique. L'incertitude du diagnostic et le manque de marqueurs périphériques précoces posent des problèmes à la recherche thérapeutique qui con...
Article
In order to evaluate genetic apolipoprotein polymorphisms as risk factors for Alzheimer's disease (AD), we studied apolipoprotein (apo) AIV after apoE, an apolipoprotein also present in the brain. The allelic distribution of apoAIV codon 360 polymorphism was no different in AD group (n = 120) compared with elderly healthy individuals (n = 119). Sur...
Article
Worldwide evidence has recently shown that the allele epsilon4 of apolipoprotein E (ApoE) is a genetic risk factor for Alzheimer's disease (AD) underlining the possible role of apoE in the physiopathology of AD. To evaluate the usefulness of apoE concentration in pathogenesis of AD, we measured the cerebrospinal fluid (CSF) levels of apoE. CSF apoE...
Article
The most promising discovery in the study of Alzheimer's disease (AD) markers is undoubtedly the implication of apolipoprotein E (apoE). The gene of this apoliprotein is located on chromosome 19 and is characterized by three common alleles epsilon 2, epsilon 3 and epsilon 4 giving raise to 6 genotypes and 6 protein phenotypes. ApoE is well known fo...

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Projects

Project (1)
Project
The miRCADE team (MicroRNAs in Cancer and Development) is a young team created early 2016 by the INSERM and HCERES. Members include senior researchers from the INSERM, CNRS, faculty from the University of Bordeaux and Polytech Institute of Bordeaux and many young international talents (postdoctorate, PhD and MS students). We study biological and molecular processes of oncogenesis in many bad prognosis pediatric and adult cancers, such as hepatocellular carcinoma, hepatoblastoma, nephroblastoma and diffuse pontine gliomas. The team uses several technical approaches and in vivo models (mouse, chick embryo, xenopus) to study many oncogenic pathways and processes including the role of microRNAs, epigenetics, metabolism, resistance to drugs and some specific signaling pathways such as Wnt, Fanconi anemia, and ERK. For instance, we have patented the use of microRNA in cancer and shown that Velcade (a proteasome inhibitor) may be a new therapeutic option for highly proliferative hepatoblastoma. The team initiated some collaborative efforts aiming at the design and the evaluation of a novel generation of targeted prodrugs capable of achieving more effective and less toxic therapeutic benefits in both pediatric and adult cancers. Under a highly anticipated regional efforts which culminate in the creating of a new cancer center in the beautiful and legendary city of Bordeaux (2022-2026), the team is intended to strengthen its presence and expand its activities. Indeed, the team will be looking forward to hosting more talented young as well as confirmed researchers. The candidates are expected to bring or initiate research projects with a fundamental, translational or technological dimension in line with our themes of investigations. Bringing new concepts or biotechnological tools will be highly appreciated (e.g. organoid, immunotherapy, high resolution microscopy). Contact : Dr Christophe Grosset or Pr Aksam Merched christophe.grosset@inserm.fr aksam.merched@u-bordeaux.fr