{"id":914,"date":"2025-01-25T15:25:22","date_gmt":"2025-01-25T15:25:22","guid":{"rendered":"https:\/\/vdjlab.com\/projects\/"},"modified":"2025-02-06T23:15:22","modified_gmt":"2025-02-06T23:15:22","slug":"projects","status":"publish","type":"page","link":"https:\/\/vdjlab.com\/index.php\/projects\/","title":{"rendered":"Projects"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"914\" class=\"elementor elementor-914\">\n\t\t\t\t<div class=\"elementor-element elementor-element-e020ae9 e-con-full e-flex e-con e-parent\" data-id=\"e020ae9\" data-element_type=\"container\" data-e-type=\"container\" data-settings=\"{&quot;background_background&quot;:&quot;classic&quot;}\">\n\t\t\t\t<div class=\"elementor-element elementor-element-f5f0d08 elementor-widget elementor-widget-heading\" data-id=\"f5f0d08\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">Projects<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-5d290b8 e-con-full e-flex e-con e-parent\" data-id=\"5d290b8\" data-element_type=\"container\" data-e-type=\"container\" data-settings=\"{&quot;background_background&quot;:&quot;gradient&quot;}\">\n\t\t<div class=\"elementor-element elementor-element-c6556f0 e-con-full e-flex e-con e-child\" data-id=\"c6556f0\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t<div class=\"elementor-element elementor-element-05699fe e-con-full e-flex e-con e-child\" data-id=\"05699fe\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-99baead elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"99baead\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Presynaptic endocytosis deficits in the pathogenesis of Parkinson\u2019s disease (PD)<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-dc21e42 elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"dc21e42\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Emerging evidence in PD genetics hints that presynaptic clathrin-mediated endocytosis (CME), which helps recycle synaptic vesicles, play a significant role in\u00a0 presynaptic degeneration of Parkinson\u2019s disease. In this study, we focus on understanding this connection using models with reduced function of a protein called auxilin.\u00a0<\/p><p>Auxilin is crucial for presynaptic CME in the neurons. Mutations in the auxilin gene can lead to a rare form of PD known as PARK19. We and others have shown that auxilin loss-of-function is an ideal model to study presynaptic CME in PD. Using auxilin knockout mice and PARK19 CRISPRed- and patient-iPSC-derived neurons, our lab is uncovering how problems in presynaptic CME may contribute to the development of PD.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-16a23cd elementor-widget__width-initial elementor-widget-mobile__width-initial elementor-widget elementor-widget-image\" data-id=\"16a23cd\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"1458\" height=\"1108\" src=\"https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/01\/CME-01.jpg\" class=\"attachment-full size-full wp-image-1373\" alt=\"\" srcset=\"https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/01\/CME-01.jpg 1458w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/01\/CME-01-300x228.jpg 300w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/01\/CME-01-1024x778.jpg 1024w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/01\/CME-01-768x584.jpg 768w\" sizes=\"(max-width: 1458px) 100vw, 1458px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-0c980b0 e-con-full e-flex e-con e-parent\" data-id=\"0c980b0\" data-element_type=\"container\" data-e-type=\"container\" data-settings=\"{&quot;background_background&quot;:&quot;gradient&quot;}\">\n\t\t<div class=\"elementor-element elementor-element-e6f9b95 e-con-full e-flex e-con e-child\" data-id=\"e6f9b95\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t<div class=\"elementor-element elementor-element-509c117 e-con-full e-flex e-con e-child\" data-id=\"509c117\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-083e7f7 elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"083e7f7\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Exploring whether mutations in LRRK2, SNCA, and GBA drive PD through presynaptic endocytosis deficits\u200b<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-e360017 elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"e360017\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p><b>LRRK2: <\/b>LRRK2, among other functions, plays a role in presynaptic endocytosis. While PD-related LRRK2 mutations inhibit key presynaptic endocytosis proteins, it is unclear whether these mutations cause PD through this pathway. We are investigating this.<\/p><p><b>SNCA (\u03b1-Synuclein): <\/b>The protein \u03b1-synuclein plays a key role in recycling synaptic vesicles and facilitating presynaptic endocytosis. While the \u03b1-synuclein\u00a0 aggregation is extensively studied in PD, the effects of its synaptic depletion are less understood. We are investigating if loss of normal \u03b1-synuclein contribute to PD by disrupting presynaptic endocytosis.<\/p><p><b>GBA: <\/b>The primary effects of GBA mutations occur in the cell body. Thus, they serve as an ideal system to study how\u00a0 cell body-specific disturbances affect presynaptic function. Our preliminary findings in GBA mutant mice show presynaptic endocytosis defects without PD-like motor symptoms. We are investigating if subtle presynaptic endocytosis deficits, when co-occur with GBA mutations, leads to PD?<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-045a23d elementor-widget__width-initial elementor-widget-mobile__width-initial elementor-widget elementor-widget-image\" data-id=\"045a23d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"1584\" height=\"1322\" src=\"https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/LRRK2-SNCA-GBA-01.jpg\" class=\"attachment-full size-full wp-image-1835\" alt=\"\" srcset=\"https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/LRRK2-SNCA-GBA-01.jpg 1584w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/LRRK2-SNCA-GBA-01-300x250.jpg 300w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/LRRK2-SNCA-GBA-01-1024x855.jpg 1024w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/LRRK2-SNCA-GBA-01-768x641.jpg 768w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/LRRK2-SNCA-GBA-01-1536x1282.jpg 1536w\" sizes=\"(max-width: 1584px) 100vw, 1584px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-2d29c6d e-con-full e-flex e-con e-parent\" data-id=\"2d29c6d\" data-element_type=\"container\" data-e-type=\"container\" data-settings=\"{&quot;background_background&quot;:&quot;gradient&quot;}\">\n\t\t<div class=\"elementor-element elementor-element-50ac967 e-con-full e-flex e-con e-child\" data-id=\"50ac967\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t<div class=\"elementor-element elementor-element-49a5026 e-con-full e-flex e-con e-child\" data-id=\"49a5026\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-7715e0d elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"7715e0d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Screening for genetic and environmental modifiers of presynaptic endocytosis<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-d54fe9d elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"d54fe9d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Several PD-linked genes and environmental toxin exposures mimic the downstream effects of presynaptic endocytosis deficits. Using SH-SY5Y cells and primary neurons from mice, we will conduct screens to identify PD-linked genes and toxins that modify presynaptic endocytosis and synaptic vesicle recycling.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-7ff20db elementor-widget__width-initial elementor-widget-mobile__width-initial elementor-widget elementor-widget-image\" data-id=\"7ff20db\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"768\" height=\"285\" src=\"https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/Screening-768x285.jpeg\" class=\"attachment-medium_large size-medium_large wp-image-1840\" alt=\"\" srcset=\"https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/Screening-768x285.jpeg 768w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/Screening-300x111.jpeg 300w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/Screening-1024x379.jpeg 1024w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/Screening-1536x569.jpeg 1536w, https:\/\/vdjlab.com\/wp-content\/uploads\/2025\/02\/Screening-2048x759.jpeg 2048w\" sizes=\"(max-width: 768px) 100vw, 768px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-e3c28ff e-con-full e-flex e-con e-parent\" data-id=\"e3c28ff\" data-element_type=\"container\" data-e-type=\"container\" data-settings=\"{&quot;background_background&quot;:&quot;gradient&quot;}\">\n\t\t<div class=\"elementor-element elementor-element-8cfa15a e-con-full e-flex e-con e-child\" data-id=\"8cfa15a\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t<div class=\"elementor-element elementor-element-c1f04f5 e-con-full e-flex e-con e-child\" data-id=\"c1f04f5\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-4400821 elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"4400821\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h3 class=\"elementor-heading-title elementor-size-default\">Effect of aging on presynaptic endocytosis: implications for susceptibility to degeneration <\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-d9e4aab elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"d9e4aab\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<p>Why nigrostriatal dopaminergic neurons have higher vulnerability to degeneration in Parkinson\u2019s disease (PD) remains unclear. Aging, the major PD risk factor, also results in nigrostriatal DA neuronal loss. This study will explore whether reduced presynaptic endocytosis underlies this vulnerability and how aging amplifies it, leading to degeneration.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Projects Presynaptic endocytosis deficits in the pathogenesis of Parkinson\u2019s disease (PD) Emerging evidence in PD genetics hints that presynaptic clathrin-mediated endocytosis (CME), which helps recycle synaptic vesicles, play a significant role in\u00a0 presynaptic degeneration of Parkinson\u2019s disease. In this study, we focus on understanding this connection using models with reduced function of a protein called [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"plain-container","ast-site-content-layout":"full-width-container","site-content-style":"unboxed","site-sidebar-style":"unboxed","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"disabled","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"enabled","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"class_list":["post-914","page","type-page","status-publish","hentry"],"_hostinger_reach_plugin_has_subscription_block":false,"_hostinger_reach_plugin_is_elementor":false,"_links":{"self":[{"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/pages\/914","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/comments?post=914"}],"version-history":[{"count":214,"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/pages\/914\/revisions"}],"predecessor-version":[{"id":2211,"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/pages\/914\/revisions\/2211"}],"wp:attachment":[{"href":"https:\/\/vdjlab.com\/index.php\/wp-json\/wp\/v2\/media?parent=914"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}