{"id":783,"date":"2023-06-28T14:38:19","date_gmt":"2023-06-28T14:38:19","guid":{"rendered":"https:\/\/website.prod.unilu.spikeseed.cloud\/lcsb-en\/?post_type=research-groups&#038;p=783"},"modified":"2025-06-18T16:13:01","modified_gmt":"2025-06-18T14:13:01","slug":"research","status":"publish","type":"research-groups","link":"https:\/\/www.uni.lu\/lcsb-en\/research-groups\/translational-neuroscience\/research\/","title":{"rendered":"Research"},"content":{"rendered":"<div class=\"section py-0 static\">\n<section class=\"py-0 wp-block-unilux-blocks-free-section section\"><div class=\"container xl:max-w-screen-xl\"><!-- SecondaryNavigationMirror --><div class=\"js-secondary-nav--sticky wp-block-unilux-blocks-secondary-navigation\" id=\"f6d7e112-b6c4-4b8d-90f4-ac9eb68462fa\">\n    <nav id=\"secondary-navigation\" role=\"navigation\" aria-label=\"Secondary menu\" class=\"secondary-nav\">\n        <button class=\"secondary-nav__button btn btn-solid--primary w-full\" aria-expanded=\"false\" aria-controls=\"secondary-navigation__list\" title=\"The selected page is Research\" type=\"button\">\n            <span class=\"btn__name mr-auto\">Research<\/span>\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--xs\">\n                <use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\" \/>\n            <\/svg>\n        <\/button>\n\n        <ul id=\"secondary-navigation__list\" class=\"secondary-nav__list\">\n            <li class=\"secondary-nav__item\">\n    <a href=\"https:\/\/www.uni.lu\/lcsb-en\/research-groups\/translational-neuroscience\/\" target=\"\" rel=\"noreferrer noopener\" class=\"secondary-nav__link \">\n        <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--xs\">\n            <use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\" \/>\n        <\/svg>\n        <span class=\"secondary-nav__name\">Overview<\/span>\n    <\/a>\n<\/li>\n<li class=\"secondary-nav__item\">\n    <a href=\"https:\/\/www.uni.lu\/lcsb-en\/research-groups\/translational-neuroscience\/research\/\" target=\"\" rel=\"noreferrer noopener\" class=\"secondary-nav__link isactived\" aria-current=\"page\">\n        <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--xs\">\n            <use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\" \/>\n        <\/svg>\n        <span class=\"secondary-nav__name\">Research<\/span>\n    <\/a>\n<\/li>\n<li class=\"secondary-nav__item\">\n    <a href=\"https:\/\/www.uni.lu\/lcsb-en\/research-groups\/translational-neuroscience\/publications\/\" target=\"\" rel=\"noreferrer noopener\" class=\"secondary-nav__link \">\n        <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--xs\">\n            <use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\" \/>\n        <\/svg>\n        <span class=\"secondary-nav__name\">Publications<\/span>\n    <\/a>\n<\/li>\n<li class=\"secondary-nav__item\">\n    <a href=\"https:\/\/www.uni.lu\/lcsb-en\/research-groups\/translational-neuroscience\/people\/\" target=\"\" rel=\"noreferrer noopener\" class=\"secondary-nav__link \">\n        <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--xs\">\n            <use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\" \/>\n        <\/svg>\n        <span class=\"secondary-nav__name\">People<\/span>\n    <\/a>\n<\/li>\n        <\/ul>\n    <\/nav>\n<\/div>\n<!-- end SecondaryNavigationMirror --><\/div><\/section>\n\n\n<section class=\"section  wp-block-unilux-blocks-content-card-full-width \">\n    <div class=\"container 2xl:max-w-screen-2xl\">\n        <div class=\"max-w-11\/12\">\n            <div class=\"content-card content-card--right content-card__overlay--hidden wp-block-unilux-blocks-content-card\">\n    \n<h2 class=\"content-card__heading has-text-align-left wp-block-unilux-blocks-heading\"        id=\"our-research\"\n    >\nOur research<\/h2>\n<div class=\"content-card__visual wp-block-unilux-blocks-content-card-visual-area\">\n    \n<section class=\"wp-block-unilux-blocks-image-video-wrapper\">\n    <figure class=\"wp-block-dev4-reusable-blocks-image  object-fit--cover\">\n    \n<img decoding=\"async\" class=\"wp-block-image unilux-custom-image-block\"\n                alt=\"\"\n            src=\"https:\/\/www.uni.lu\/wp-content\/uploads\/sites\/6\/2023\/06\/Translational-Neuroscience-V2.jpg\"\n                srcset=\"https:\/\/www.uni.lu\/wp-content\/uploads\/sites\/6\/2023\/06\/Translational-Neuroscience-V2-300x228.jpg 300w, https:\/\/www.uni.lu\/wp-content\/uploads\/sites\/6\/2023\/06\/Translational-Neuroscience-V2-1024x777.jpg 1024w, https:\/\/www.uni.lu\/wp-content\/uploads\/sites\/6\/2023\/06\/Translational-Neuroscience-V2-768x583.jpg 768w, https:\/\/www.uni.lu\/wp-content\/uploads\/sites\/6\/2023\/06\/Translational-Neuroscience-V2-1536x1166.jpg 1536w, https:\/\/www.uni.lu\/wp-content\/uploads\/sites\/6\/2023\/06\/Translational-Neuroscience-V2-2048x1555.jpg 2048w\"\n                style=\"object-position: 50.00% 15.00%; font-family: &quot;object-fit: cover; object-position: 50.00% 15.00%;&quot;; aspect-ratio: 3\/2; object-fit: cover; width: 100%;\"\n        loading=\"lazy\"\n\/>    <\/figure><\/section>\n<div class=\"wp-block-unilux-blocks-wrapper content-card__overlay\">\n<a class=\"wp-block-unilux-blocks-button-highlight-rounded bottom-left\" \n    href=\"#\"\n    target=\"_self\"\n>\n    \n<span class=\"btn-highlight-rounded__name wp-block-unilux-blocks-plain-text\"><\/span>    <span class=\"icon-rounded\">\n        <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-right icon--lg\"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\"><\/use><\/svg>    <\/span>\n<\/a><\/div>\n<\/div><div class=\"content-card__body  wp-block-unilux-blocks-content-card-free-area\">\n    \n<div class=\"wp-block-columns is-layout-flex wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p>Our group carries out fundamental research, clinical research, and integrative care concepts. The fundamental research focus is the elucidation of molecular signalling pathways leading to neurodegeneration in Parkinson&#8217;s disease (PD). Using comprehensive genetic analyses in a large sample of Parkinson patients via whole genome sequencing and genome-wide association studies, we have identified novel mutations in genes that are responsible for familial PD and deciphered genetic variants in candidate genes that are associated with sporadic PD.<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p>The clinical research focus is part of the National Centre for Excellence in Research on Parkinson\u2019s Disease (NCER-PD), an initiative of the Luxembourg National Research Fund (FNR). Patients and healthy subjects from Luxembourg and the Greater Region are recruited for a cohort and can directly contribute to PD research by donating biological samples (e.g., DNA, skin). Together with the Centre Hospitalier de Luxembourg (CHL), the Luxembourg Institute of Health (LIH) with the Integrated Biobank of Luxembourg (IBBL), we perform clinical characterisation and biosampling of PD patients.<\/p>\n\n\n\n<p>The Translational Neuroscience Group was established under the auspices of FNR\u2019s PEARL Programme.&#8221;<\/p>\n<\/div>\n<\/div>\n<\/div><\/div>        <\/div>\n    <\/div>\n<\/section>\n\n\n<section class=\"py-0 wp-block-unilux-blocks-free-section section\"><div class=\"container xl:max-w-screen-xl\">\n<h2 class=\"has-text-align-left wp-block-unilux-blocks-heading\"        id=\"our-research-projects\"\n    >\nOur Research projects<\/h2>\n\n\n\n<p>The Translational Neuroscience group combines fundamental and clinical research and Integrated care concepts:<\/p>\n<\/div><\/section>\n\n\n\n<section class=\"py-0 wp-block-unilux-blocks-free-section section\"><div class=\"container xl:max-w-screen-xl\">\n<div class=\"wp-block-unilux-blocks-accordion accordion accordion--theme accordion-standard\" data-reference=\"163a6546-58f4-4523-b618-5e2c17dcc65b\" data-accordion-type=\"standard\"><div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-491f1b87-64c2-4a49-b7e3-43291b2a8529\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-491f1b87-64c2-4a49-b7e3-43291b2a8529\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-491f1b87-64c2-4a49-b7e3-43291b2a8529\"\n        >\n            <span class=\"accordion__title\">\n                                Role of DJ-1\/PARK7 in the immunopathogenesis of Parkinson\u2019s disease            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-491f1b87-64c2-4a49-b7e3-43291b2a8529\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-491f1b87-64c2-4a49-b7e3-43291b2a8529\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>April 2021 &#8211; April 2025<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><a href=\"https:\/\/www.lih.lu\/fr\/soutien-a-la-recherche\/formation-doctorale\/i2tron\/\">FNR PRIDE DTU I2TRON program<\/a><\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr Ibrahim BOUSSAAD, Vera TSLAF<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Feng HE (LIH), Markus OLLERT (DII \u2013 LIH)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>It has been established that DJ-1 deficiency alters peripheral T cell compartment leading to an increase of na\u00efve T cells and reduction of memory T lymphocytes and Tregs <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35618940\/\">(Danileviciute et al., 2022<\/a>; <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35037711\/\">Zeng et al., 2022<\/a>). Using human induced pluripotent stem cells (iPSC)-derived DJ-1 deficient neurons and isogenic control, we aim to investigate whether DJ-1 deficient neurons demonstrate an altered susceptibility to immune milieu. Immune system relevant markers and pathways were examined using RNA sequencing (RNA-seq) data obtained from the isogenic neuronal pair, and the differential expression of the identified markers is being currently validated in the <em>in vitro<\/em> cultures. Additionally, via <em>in vitro<\/em> co-culture model between the isogenic neuronal pair and primary human T lymphocytes, we aim to investigate whether DJ-1 deficient neurons show altered susceptibility to T cell immune response.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-71fea478-c1e8-4147-8a8e-02c2ea8e61c8\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-71fea478-c1e8-4147-8a8e-02c2ea8e61c8\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-71fea478-c1e8-4147-8a8e-02c2ea8e61c8\"\n        >\n            <span class=\"accordion__title\">\n                                Disease Modifiers in LRRK2 Parkinson&#8217;s Disease            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-71fea478-c1e8-4147-8a8e-02c2ea8e61c8\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-71fea478-c1e8-4147-8a8e-02c2ea8e61c8\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>ongoing<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><a href=\"https:\/\/give.michaeljfox.org\/give\/489725\/?gad_source=1&amp;gclid=Cj0KCQjw0ruyBhDuARIsANSZ3wrur8EcpyB8S02CbBmNMqVidxDHHOGyrjR9v7vq0VxTUyw9iYSli4AaAkewEALw_wcB#!\/donation\/checkout?utm_source=google&amp;utm_medium=cpc&amp;utm_term=mjffgeneral&amp;utm_campaign=annualgiving_donationkeywords_us__search_google&amp;c_src=smcidoc-a1bVL000001GC7t\">Michael J Fox Foundation<\/a><\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>&nbsp;Dr. Jochen OHNMACHT<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Center for Systems and Therapeutics and the Taube\/Koret Center for Neurodegenerative Disease Research at Gladstone Institutes<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Parkinson\u2019s disease (PD) is the most frequent neurodegenerative movement disorder. While several genes causative for familial forms of PD as well as risks factors have already been identified, it is still unclear how patient\u2019s genomes shape their predisposition to develop PD. For example, despite sharing the same mutation in the <em>LRRK2<\/em> gene \u2013 the most common cause of late-onset familial PD \u2013 carriers display broad variation in severity of symptoms as well as the time of disease onset. To address this observed and unexplained variation, the LCSB takes part in an international effort, collaborating with partners in several European countries, to study families sharing both a history of PD and a G2019S mutation in the <em>LRRK2<\/em> gene. By comparing clinical data and genetic profiles of patients a list of susceptibility factors has been generated (ongoing collaboration with Dr. Enrico Glaab and Dr. Patrick May at the LCSB). We are investigating the effects of these susceptibility factors on PD-related phenotypes using iPSC derived dopaminergic neuron cultures from PD patients and healthy controls .<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-382de9bc-a5ee-477c-84d4-e63f63005629\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-382de9bc-a5ee-477c-84d4-e63f63005629\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-382de9bc-a5ee-477c-84d4-e63f63005629\"\n        >\n            <span class=\"accordion__title\">\n                                Pink-1-related molecular mechanisms to dissect the connection between Type 2 diabetes (T2D) and insulin resistance in PD            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-382de9bc-a5ee-477c-84d4-e63f63005629\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-382de9bc-a5ee-477c-84d4-e63f63005629\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>January 2022 to August 2024<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><a href=\"https:\/\/www.fnr.lu\/\">Fonds National de Recherche (FNR)<\/a> &#8211; (CORE Junior grant to Giuseppe ARENA)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr. Giuseppe ARENA, Alexandre BARON<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Enza Maria VALENTE (University of Pavia, Italy), Miriam CNOP (Universit\u00e9 Libre de Bruxelles, Belgium), Axel METHNER (University of Mainz, Germany)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Epidemiological studies indicate that patients with T2D have an increased risk of developing Parkinson&#8217;s disease (PD). These two age-related chronic diseases share similar alterations in essential biological processes and molecular networks, suggesting common mechanisms underlying their pathogenesis. Mutations in the mitochondrial kinase PINK1 are the second most frequent cause of autosomal recessive PD. Based on the compelling evidence implicating PINK1 also in T2D, we decided to use complementary PINK1-deficient cellular models (PINK1-mutant iPSC-derived dopaminergic neurons and PINK1-silenced pancreatic \u03b2-cells) as prototype to decipher the cellular alterations leading to neurodegeneration in PD and \u03b2-cells failure in T2D, trying to clarify the functional interdependencies between the two diseases. Findings obtained from this project will allow the identification of novel potential therapeutic targets, thus contributing to patient-based biomedical research in both fields.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-fbaba46f-169d-4705-ac24-4ba94a89cefb\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-fbaba46f-169d-4705-ac24-4ba94a89cefb\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-fbaba46f-169d-4705-ac24-4ba94a89cefb\"\n        >\n            <span class=\"accordion__title\">\n                                DJ-1 and molecular pathways            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-fbaba46f-169d-4705-ac24-4ba94a89cefb\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-fbaba46f-169d-4705-ac24-4ba94a89cefb\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>ongoing<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><a href=\"https:\/\/www.fnr.lu\/\">Fonds National de Recherche (FNR)<\/a> within the PEARL Excellence Program [FNR\/P13\/6682797], Jean Think Foundation Luxembourg, FNR [AFR PhD 12447024], Jump.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr. Ibrahim BOUSSAAD, Fran\u00e7ois MASSART, Pauline MENCKE<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Johannes MEISER<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Familial forms of Parkinson\u2019s disease (PD) offer the opportunity to generate human cell models based on induced pluripotent stem cell (iPSC) technology to study the pathophysiology of the disease. These models are used to identify molecular pathways involved in PD and to gain general insights not only into familial but also into idiopathic PD. One of the causes of familial PD is homozygous loss-of-function mutations of DJ-1. DJ-1, a protein encoded by the gene PARK7, has broad biological functions including effects on mitochondrial and lysosomal homeostasis (Krebiehl et al.). We have previously shown that fibroblasts obtained from PD patients carrying the homozygous mutation c.192G&gt;C in the DJ-1 gene display a phenotype of impaired mitochondrial respiration, increased intra-mitochondrial reactive oxygen species, reduced basal autophagy and the accumulation of defective mitochondria.<br><br>In order to study the effect of DJ-1 loss of function on PD target cells, midbrain-specific dopaminergic (mDA) neurons, astrocytes and microglia, we have generated iPSC from these fibroblasts that are used in state-of-the-art differentiation protocols. Using pairs of disease-specific and isogenic control iPSC we\u2019re identifying cellular phenotypes that can be used as read out for small chemical compound library screens. Furthermore, we are studying the metabolic implications for the cell caused by loss of DJ-1 in PD cell models and caused by DJ-1 upregulation in glioblastoma multiforme cell models.<br>Results have been published in Science Translational Medicine in September 2020.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-b1efc969-a06d-415f-8d6a-ac4a561b6823\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-b1efc969-a06d-415f-8d6a-ac4a561b6823\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-b1efc969-a06d-415f-8d6a-ac4a561b6823\"\n        >\n            <span class=\"accordion__title\">\n                                The relevance of Miro1 for mitochondrial function and dynamics in PD            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-b1efc969-a06d-415f-8d6a-ac4a561b6823\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-b1efc969-a06d-415f-8d6a-ac4a561b6823\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>October 2023 &#8211; October 2024<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>FNR (Mirisk-PD CORE grant to Rejko Kr\u00fcger) and &#8220;King Baudouin Foundation United States&#8221; (to Rejko Kr\u00fcger and Giuseppe Arena)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr. Giuseppe ARENA, Dr. Daniele FERRANTE, Alexandre BARON<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Acurex Biosciences<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Miro1 is a cytosolic calcium sensor anchored to the outer mitochondrial membrane (OMM) that plays a pivotal role in the regulation of mitochondrial dynamics and quality control (doi:10.3389\/fneur.2020.00587). We identified and functionally characterized&nbsp;first PD-associated heterozygous mutations in the RHOT1&nbsp;gene encoding Miro1: (i) c.815G&gt;A \u00e0&nbsp;Miro1 R272Q; (ii) c.1348C&gt;T \u00e0&nbsp;Miro1 R450C; (iii) c.1290A&gt;G \u00e0&nbsp;Miro1 T351A; (iv) c.2067A&gt;G \u00e0&nbsp;Miro1 T610A. Our findings in primary skin fibroblasts pointed to calcium dyshomeostasis as a major shared hallmark between the four PD-related mutations in patients with a positive family history of PD (doi:10.1089\/ars.2018.7718; doi:10.3390\/jcm8122226). <\/p>\n\n<p>Moreover, induced pluripotent stem cells (iPSC)-derived neurons and 3D midbrain organoids from the Miro1 R272Q patient displayed impaired mitochondrial bioenergetics and higher \u03b1-synuclein levels compared to the respective isogenic, gene-corrected controls. This was accompanied by a significant loss of dopaminergic neurons both in Miro1 R272Q organoids and in the substantia nigra of 15-months old mice expressing the orthologous, Miro1 R285Q mutation, finally leading to impaired anterograde procedural memory (doi:10.1101\/2023.12.19.571978). <\/p>\n\n<p>We are now extending our analyses to iPSC-derived neurons from PD patients carrying distinct Miro1 mutations in different functional domains of the protein, aimed at exploring the potential interplay between Miro1 and \u03b1-synuclein, including the modulations of calcium channels.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-c0e22956-f74f-4918-a70e-bc7c5ef696bb\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-c0e22956-f74f-4918-a70e-bc7c5ef696bb\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-c0e22956-f74f-4918-a70e-bc7c5ef696bb\"\n        >\n            <span class=\"accordion__title\">\n                                The role of the retromer in Parkinson\u2019s disease neuroinflammation            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-c0e22956-f74f-4918-a70e-bc7c5ef696bb\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-c0e22956-f74f-4918-a70e-bc7c5ef696bb\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>February 2023 &#8211; ongonig<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>FNR <a href=\"https:\/\/www.lih.lu\/en\/research-support\/doctoral-training\/nextimmune2\/\">NextImmune2<\/a> Doctoral Training Unit (PRIDE21\/16749720\/NEXTIMMUNE2),&nbsp;LCSB Tandem Funding Scheme<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Ioanna BOUMPOUREKA, Dr Vyron GORGOGIETAS<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Prof. Dr.&nbsp;Wim VANDENBERGHE (KU Leuven), Dr.&nbsp;Enrico GLAAB (LCSB)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene, encoding the core component of the retromer complex, have been identified as a cause of late-onset autosomal dominant Parkinson\u2019s disease (PD). So far, a single missense mutation, Asp620Asn (D620N), has been unambiguously identified to cause PD in multiple individuals and families worldwide (<a href=\"https:\/\/doi.org\/10.1016\/j.ajhg.2011.06.008\">Zimprich et al., 2011<\/a>; <a href=\"https:\/\/doi.org\/10.1016\/j.ajhg.2011.06.001\">&nbsp;Vilari\u00f1o-G\u00fcell et al., 2011<\/a>). The retromer is responsible for the trafficking and localization of various proteins within the cell, via two key&nbsp;pathways: the endosome-to-Golgi retrograde transport pathway and the endosome-to-cell-membrane recycling pathway. <\/p>\n\n<p>Various retromer cargos have been identified to date, pointing to the retromer&#8217;s indirect, yet important role in numerous cellular functions (<a href=\"https:\/\/doi.org\/2010.3233\/JPD-161020\">Williams et al., 2017<\/a>).&nbsp;The exact molecular mechanisms underlying VPS35-induced neurodegeneration are still under investigation. Our team has previously shown&nbsp;perturbed mitochondrial respiration, lysosomal dysfunction, and a-synuclein accumulation in&nbsp;induced pluripotent stem cell (iPSC)-derived neurons (<a href=\"https:\/\/doi.org\/10.1002\/mds.28365\">Hanss et al., 2021<\/a>).&nbsp;Recently, several studies have linked VPS35 deficiency to perturbed microglial activation and inflammatory phenotypes in immortalized cell lines (<a href=\"https:\/\/doi.org\/10.1016\/j.neuron.2013.06.046\">Lucin et al., 2013<\/a>; <a href=\"https:\/\/doi.org\/10.1111\/tra.12451\">Yin et al., 2016<\/a>) and mouse models of Alzheimer&#8217;s disease and ischemic stroke (<a href=\"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-022-02422-0\">Ren et al., 2022<\/a>; <a href=\"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-019-1633-y\">Ye et al., 2019<\/a>). <\/p>\n\n<p>However, no studies so far have assessed the roles of mutant&nbsp;VPS35 in microglial models of PD. With this project, we aim to uncover the novel role of the retromer in immune regulation in&nbsp;iPSC-derived microglial cells from patients with familial PD, and their respective isogenic controls,&nbsp;using&nbsp;wet lab techniques, integrated proteomics and metabolomics experiments, and bioinformatics tools.<\/p>\n\n<p>Poster presentation \u2018Uncovering the role of p.D620N VPS35 in immune regulation in a patient-derived microglial model of familial Parkinson\u2019s disease\u2019 in the <a href=\"https:\/\/meetings.embo.org\/event\/24-microglia\">EMBO Workshop \u2018Microglia in Health and Disease\u2019<\/a>, Genoa, May 2024.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-cf4ab4b0-6f75-4e22-8664-9435d0347129\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-cf4ab4b0-6f75-4e22-8664-9435d0347129\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-cf4ab4b0-6f75-4e22-8664-9435d0347129\"\n        >\n            <span class=\"accordion__title\">\n                                Pathological role of \u03b1-Synuclein in Parkinson\u2019s Disease            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-cf4ab4b0-6f75-4e22-8664-9435d0347129\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-cf4ab4b0-6f75-4e22-8664-9435d0347129\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\n<br>Duration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>2018 &#8211; 2024<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>FNR BRIDGES (MOTASYN), FNR INTERCORE (MAMASYN)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr. Vyron GORGOGIETAS, Dr. Ibrahim BOUSSAAD, Dr. Jochen OHNMACHT,&nbsp;Ioanna BOUMPOUREKA<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Ksilink (France), Prof. Przedborski (Columbia University), Dr. Michel MITTELBRONN (LCSB\/UL), Dr. Anne GRUNEWALD (LCSB\/UL)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Following the discovery that SNCA encodes \u03b1-synuclein (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/9197268\/\">Polymeropoulos et al., 1997<\/a>) in an A53T autosomal dominant form of inheritance in a familial case of PD, a further five other point mutations have been identified in families with hereditary PD: A30P (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/9462735\/\">Kruger et al., 1998<\/a>), E46K (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/14755719\/\">Zarranz et al., 2004<\/a>), H50Q, (<a href=\"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.25421\">Appel-Cresswell et al., 2013<\/a>), G51D (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/23526723\/\">Lesage et al., 2013<\/a>) and A53E (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/24746362\/\">Pasanen et al., 2014<\/a>). Furthermore, duplications and triplications of SNCA have been identified leading to the clinical manifestation of the disease, with the triplication of SNCA leading to an earlier disease onset and increased diseased severity. Several Genome-Wide Association Studies (GWAS) have also implicated the variability at the SNCA locus as a major risk factor in idiopathic PD (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2787725\/\">Simon-Sanchez et al., 2009<\/a>). The oligomerization of the monomeric \u03b1-synuclein into toxic aggregates of amyloid-like fibrils is one of the main pathogenic features of \u03b1-synuclein, which is a major constituent of LB (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/9726379\/\">Spillantini et al., 1998<\/a>).<\/p>\n\n<p>Our panel of patient-derived iPSC lines includes SNCA point mutations (A30P, A53T) or gene copy number alterations (duplication and triplication). We have generated a set of isogenic corrected cell lines and have introduced SNCA point mutations into age- and gender-matched healthy controls. Exploring PD-related phenotypes in dopaminergic neuron cultures, our particular focus is on aSyn roles at membranes, e.g. mitochondria\/ER and exosomes.<\/p>\n\n<p>Based on these phenotypes we are developing assays to screen in high-throughput small molecule libraries for early drug discovery and drug repurposing studies. In this context, using patient-derived SNCA triplication-derived neurons and their isogenic controls, we were able to identify phenotypic and molecular (mitochondrial)-based profiles and perform drug-repurposing studies, based on these readouts. We identified and validated the effect of promising compounds and we proposed the Mode-of-Action, respectively. Moreover, using the patient-derived SNCA mutations (A53T, A30P) neurons, we were able to validate-characterize these models and identify multiple neuronal phenotypes, that can be further used both for evaluation of the effect of \u03b1-synuclein in the ER-to-mitochondria axis and for drug repurposing studies. These projects were collaborations between our group and industrial partners and\/or other international research institutes. <\/p>\n\n<p>Considering the role of \u03b1-synuclein spreading in PD\u2019s pathophysiology, we study the role of exosomes in PD. Scientists progressively study exosomes as they are a great, innovative, and promising tool for a better understanding of Parkinson\u2019s disease (PD), but also a great tool for prognosis, diagnosis, and even drug treatment. Exosomal-based study of PD is promising, as it can reveal the spreading of PD pathophysiology in the brain. Based on our results, we are able to deeper understand the mechanisms participating in \u03b1-synuclein spreading and identify exosomal cargo alterations (exosomal &#8220;signatures&#8221;), that can possibly reveal putative PD-related biomarkers (including proteins, DNAs, RNAs, metabolites and lipids). Although we use PD-patient iPSC-derived neuronal models for our exosomal studies, our procedures can further be applied to clinical samples, as prognostic and diagnostic tools. Exosomal signatures can be correlated with specific PD cases, and response to treatment against PD symptoms, but can also be used as targets for new therapeutic approaches.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-0d713eb6-4801-4a7c-beba-89dad638e112\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-0d713eb6-4801-4a7c-beba-89dad638e112\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-0d713eb6-4801-4a7c-beba-89dad638e112\"\n        >\n            <span class=\"accordion__title\">\n                                Prodromal DEtErminants for PhENoconversion of idiopathic RBD to alpha-synucleinopathies (PD, DLB and MSA) &#8211; DEEPEN-iRBD (ERA-NET PerMed)            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-0d713eb6-4801-4a7c-beba-89dad638e112\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-0d713eb6-4801-4a7c-beba-89dad638e112\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\nDuration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>January 1st, 2023 (Scientific start date: February 1st), for 3 years<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>ERA PerMed project funded by <a href=\"https:\/\/www.fnr.lu\/funding-instruments\/inter\/\">INTER\/FNR<\/a><\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr. Rejko Kr\u00fcger, Dr. Yahya Salem, Fran\u00e7ois Massart<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Universit\u00e0 degli Studi di Milano (Italy), IRCCS Istituti Clinici Scientifici Maugeri di Milano (Italy), Lund University (Sweden),Commissariat \u00e0 l\u2019Energie Atomique et aux \u00e9nergies alternatives (France), University of Copenhagen (Denmark), The Danish Parkinson&#8217;s Association (Denmark), University of Zagreb (Croatia)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Evidence shows that individuals affected by idiopathic REM (Rapid Eye Movement) sleep behavior disorder (iRBD) have a high risk of conversion to Parkinson\u2019s disease, dementia with Lewy bodies, or multiple system atrophy. Despite sharing a cellular pathological hallmark, the aggregation of alpha-synuclein, and some clinical features in the early stages, these conditions show different phenotypes in later stages with significant therapeutic and prognostic consequences for the patients.<\/p>\n\n<p>The consortium DEEPEN-iRBD aims to develop a pathogenicity model for prediction of phenoconversion utilizing pre-clinical\/clinical research and data analysis, taking into account a personalized medicine approach, based on the individual\u2019s unique characteristics and optimization of strategies for the prevention, diagnosis and treatment of the individuals rather than the disease.<\/p>\n\n<p>In this project, both existing and newly acquired data will be integrated, including advanced clinical assessments, physiological signal recordings, molecular markers derived from body fluids, skin biopsy, and iPSC-derived brain cells, in order to identify a specific profile at a very early stage, that is a prodromal phase, for each of the above conditions. This would ultimately allow to define a model for early risk stratification, diagnosis, treatment, and prognosis of patients with iRBD.&nbsp;<\/p>\n\n<p>A further important objective of the project deals with the ethical and social aspects of screening people in a prodromal stage of the diseases and of communicating the screening results.<\/p>\n\n<p><strong>Communication channels:<\/strong><\/p>\n\n<p>Twitter account-project: @DEEPEN_iRBD, <a href=\"https:\/\/twitter.com\/DEEPEN_iRBD\">https:\/\/twitter.com\/DEEPEN_iRBD<\/a><\/p>\n\n<p>LinkedIn account: DEEPEN iRBD, <a href=\"https:\/\/www.linkedin.com\/posts\/deepen-irbd-877140268_deepen-irbd-project-kick-off-meeting-at-universit\u00e0-activity-7035967818357432320-yZkJ\/?trk=public_profile_like_view\">DEEPEN-iRBDLinkedIn<\/a><\/p>\n\n<p><strong>Main implications of the University of Luxembourg<\/strong><\/p>\n\n<p>In WP1 \u201cManagement and dissemination\u201d, UniLu is a co-lead in the project management and a member of the project management committee responsible for establishing and providing documents and technical support. UniLu is a lead in data protection, will coordinate the establishment of the Data Management Plan and will support the consortium with the IT infrastructure at UNILU that will be used in sharing and distributing data across partners.<\/p>\n\n<p>In WP2 \u201cMolecular and neurophysiological profiling and clinical data integration\u201d, UniLu is the lead of the WP and a co-lead in clinical data processing of data from individuals with polysomnography (PSG) validated iRBD participating in nation-wide REM-Sleep Behaviour Disorder Study. The iRBD cohort will be assessed on an annual basis (pre- and post-phenoconversion) with deep clinical (neurological and neuropsychological test battery) assessment and accompanied by biofluid collection and skin biopsy, thus patients be seen in this context. Data from iRBD patients with high risk of conversion will be complemented by longitudinal data and biosamples from more than 800 patients with PD, MSA and DLB from the Luxembourg Parkinson\u2019s Study (NCER-PD) collected since 2015. UNILU will stratify iRBD cohort with NeuroChip (Illumina) and targeted sequencing of GBA gene (PacBio) to provide and cover the most frequent genetic risk factors in iRBD as well as in PD and DLB. Overnight PSG will be performed and interpreted according to standard guidelines at UNILU. Evaluation of the cardiovascular neural control in iRBD patients will be performed from the PSG recordings collected by UNILU.<\/p>\n\n<p>In WP3 \u201cBio-samples processing\u201d, UniLu will provide biological samples from patients whose pathology is characterized. In addition, UniLu provides and characterizes iPSC-derived brain cell types<\/p>\n\n<p>generated from fibroblasts of RBD patients and healthy controls and will transfer the data obtained to Lund University for pathogenicity model implementation and prediction of phenoconversion from iRBD.<\/p>\n\n<p><strong>Press release:<\/strong><\/p>\n\n<p>ERA PerMed published a newsletter on the ERA PerMed website with the results of this call and public abstracts of the funded projects: <a href=\"https:\/\/erapermed.isciii.es\/wp-content\/uploads\/2023\/02\/Newsletter-January-23_final1.pdf\">erapermed\/2023\/Newsletter<\/a><\/p>\n\n<p><a href=\"https:\/\/www.era-learn.eu\/network-information\/networks\/era-permed\/5th-joint-transnational-call-for-proposals-2022\/prodromal-determinants-for-phenoconversion-of-idiopathic-rbd-to-alpha-synucleinopathies-pd-dlb-and-msa\">EraPerMed-DEEPEN-iRBD<\/a><\/p>\n\n<p>The tweet from ERA PerMed can be found here: <a href=\"https:\/\/twitter.com\/ERANET_PerMed\/status\/1617838455127699456\">twitter.com\/ERANET_PerMed<\/a><\/p>\n\n<p><a href=\"https:\/\/parkinson.lu\/news-events\/news\/rbd-deepen\">Parkinson.lu\/DEEPEN-iRBD<\/a><\/p>\n\n<p><a href=\"https:\/\/www.uni.lu\/lcsb-fr\/news\/differentiating-typical-and-atypical-parkinsonism-early-in-disease\/\">UNILI\/DEEPEN-iRBD<\/a><\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div class=\"accordion__item  wp-block-unilux-blocks-accordion-item\">\n    <h3 class=\"accordion__header\"\n        >\n        <button\n            type=\"button\"\n            id=\"accordion-labelledby-80fbfb23-050c-44e9-a64d-4b0068e7fcf2\"\n            class=\"accordion__button collapsed\"\n            aria-expanded=\"false\"\n            aria-controls=\"accordion-panel-80fbfb23-050c-44e9-a64d-4b0068e7fcf2\"\n            data-bs-toggle=\"collapse\"\n            data-bs-target=\"#accordion-panel-80fbfb23-050c-44e9-a64d-4b0068e7fcf2\"\n        >\n            <span class=\"accordion__title\">\n                                Stratification of idiopathic Parkinson&#8217;s disease (PD) based on pathway-specific Polygenic Risk Scores            <\/span>\n\n            <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-down \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-down\"><\/use><\/svg>        <\/button>\n    <\/h3>\n    <div id=\"accordion-panel-80fbfb23-050c-44e9-a64d-4b0068e7fcf2\"\n        class=\"accordion__collapse collapse\"\n        aria-labelledby=\"accordion-labelledby-80fbfb23-050c-44e9-a64d-4b0068e7fcf2\"\n        data-bs-parent=\"[data-reference=&quot;163a6546-58f4-4523-b618-5e2c17dcc65b&quot;]\"\n    >\n        <div class=\"accordion__body \">\n            \n<ul class=\"wp-block-unilux-blocks-highlighted-list list-highlighted list-highlighted--course\"><li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"duration\"\n    >\n<br>Duration:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>February 2019 &#8211; February 2027<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"funding-source\"\n    >\nFunding source:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><a href=\"https:\/\/www.fnr.lu\/\">Fonds National de Recherche (FNR)<\/a> (Mirisk-PD CORE to Rejko Kr\u00fcger and AFR bilateral to Rejko Kr\u00fcger and Anne Gr\u00fcnewald)<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"researchers\"\n    >\nResearchers:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Dr. Giuseppe ARENA, Alexandre BARON, I\u00f1igo Yoldi BERGUA, Vyron GORGOGIETAS<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"partners\"\n    >\nPartners:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Christine KLEIN, Joanne TRINH &amp; Philip Seibler (University of Lubeck), Bas BLOEM &amp; Marcel VERBEECK (Radboud University Medical Centre, Nijmegen, The Netherlands), Thomas FOLTYNIE (Institute of Neurology, University College London), Oliver BANDMANN &amp; Thomas PAYNE (Sheffield University), Manu SHARMA &amp; Ashwin Ashok Kumar Sreelatha (University of Tuebingen), Nico DIEDERICH (Centre Hospitalier de Luxembourg), Ziv GAN-OR &amp; Ted FON (McGill University, Montreal, Canada), Zied LANDOUSLI, Dajana GROSSMANN, Armelle VITALI, Sylvie DELCAMBRE, Paul ANTONY, Ibrahim Boussaad, Dheeraj Reddy BOBBILI, Lukas PAVELKA, Enrico GLAAB,&nbsp;Patrick MAY &amp; Anne GR\u00dcNEWALD (University of Luxembourg).<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"description\"\n    >\nDescription:<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p>Given the large body of evidence pointing to mitochondrial dysfunction and lysosomal impairment as causative events in PD pathogenesis, these two organelles emerged early as logical targets for disease-modifying treatments in PD. &nbsp;However, to date, all PD clinical trials applying drugs targeting mitochondrial (e.g., Coenzyme Q) or lysosomal (e.g., Ambroxol) pathways to unselected patient groups failed. In this light, genetic stratification of mitochondrial or lysosomal risk could help to define subgroups of idiopathic PD (iPD) patients, who may be more responsive to therapeutic compounds targeting mitochondrial or lysosomal defects, respectively. Here, we use computational approaches based on mitochondria- or lysosome-specific polygenic risk scores (mitoPRSs, lysoPRSs) to assess the synergistic effect of common variants in nuclear-encoded mitochondrial or lysosomal genes on PD risk. Importantly, we functionally validate PRS profiles in cellular models from iPD patients with high or low risk, paving the way for translating genetic prediction into more targeted therapeutic treatments.<\/p>\n<\/div><\/div><\/li>\n\n<li class=\"list-highlighted__item  items-start wp-block-unilux-blocks-highlighted-list-item\">\n    <header class=\"list-highlighted__header wp-block-unilux-blocks-highlighted-list-item-header\">\n    \n<h4 class=\"title text-18 font-bold has-text-align-left wp-block-unilux-blocks-heading\"        id=\"project-details-pdf\"\n    >\nProject details (PDF):<\/h4>\n<div class=\"wp-block-unilux-blocks-bigtext\">\n    <span>\n        \n    <\/span>\n<\/div><\/header><div class=\"list-highlighted__body wp-block-unilux-blocks-highlighted-list-item-body\">\n    <div class=\"wp-block-unilux-blocks-highlighted-list-item-free-content-area\">\n    \n<p><a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.26949\" target=\"_blank\" rel=\"noreferrer noopener\">Read the paper<\/a><\/p>\n<\/div><\/div><\/li><\/ul>\n        <\/div>\n    <\/div>\n<\/div><\/div>\n<\/div><\/section>\n\n\n<section class=\"section section wp-block-unilux-blocks-quick-link-discover-section\">\n    <div class=\"container xl:max-w-screen-xl\">\n        \n<h2 class=\"has-text-align-left wp-block-unilux-blocks-heading\"        id=\"discover-more\"\n    >\nDiscover more<\/h2>\n\n<ul class=\"wp-block-unilux-blocks-quick-link-discover quick-link-list\">\n<li class=\"wp-block-unilux-blocks-quick-link-discover-item\">\n    <a\n                    href=\"https:\/\/www.uni.lu\/lcsb-en\/research\"\n                    class=\"quick-link\"\n            target=\"\"\n    >\n            <span class=\"quick-link__container\">\n                <span class=\"quick-link__text\">\n                    Research at the LCSB                <\/span>\n                <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-right \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\"><\/use><\/svg>            <\/span>\n    <\/a>\n<\/li>\n\n\n\n<li class=\"wp-block-unilux-blocks-quick-link-discover-item\">\n    <a\n                    href=\"https:\/\/www.uni.lu\/lcsb-en\/join-us\/\"\n                    class=\"quick-link\"\n            target=\"\"\n    >\n            <span class=\"quick-link__container\">\n                <span class=\"quick-link__text\">\n                    Join us                <\/span>\n                <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-right \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\"><\/use><\/svg>            <\/span>\n    <\/a>\n<\/li>\n\n\n\n<li class=\"wp-block-unilux-blocks-quick-link-discover-item\">\n    <a\n                    href=\"https:\/\/www.uni.lu\/lcsb-en\/contact\/\"\n                    class=\"quick-link\"\n            target=\"\"\n    >\n            <span class=\"quick-link__container\">\n                <span class=\"quick-link__text\">\n                    Contact us                <\/span>\n                <svg aria-hidden=\"true\" focusable=\"false\" class=\"icon icon-outline icon--arrow-right \"><use xlink:href=\"https:\/\/www.uni.lu\/wp-content\/themes\/unilux-theme\/assets\/images\/icons\/icons-outline.svg#icon--arrow-right\"><\/use><\/svg>            <\/span>\n    <\/a>\n<\/li>\n<\/ul>\n    <\/div>\n<\/section><\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":39,"featured_media":0,"parent":535,"menu_order":0,"template":"","meta":{"featured_image_focal_point":[],"show_featured_caption":false,"ulux_newsletter_groups":"","uluxPostTitle":"Translational Neuroscience","uluxPrePostTitle":"Research Group","_trash_the_other_posts":false,"_price":"","_stock":"","_tribe_ticket_header":"","_tribe_default_ticket_provider":"","_tribe_ticket_capacity":"0","_ticket_start_date":"","_ticket_end_date":"","_tribe_ticket_show_description":"","_tribe_ticket_show_not_going":false,"_tribe_ticket_use_global_stock":"","_tribe_ticket_global_stock_level":"","_global_stock_mode":"","_global_stock_cap":"","_tribe_rsvp_for_event":"","_tribe_ticket_going_count":"","_tribe_ticket_not_going_count":"","_tribe_tickets_list":"[]","_tribe_ticket_has_attendee_info_fields":false},"field-of-interest":[],"organisation":[],"authorship":[39],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v22.3 (Yoast SEO v22.3) - 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