{"id":107,"date":"2022-12-15T17:48:43","date_gmt":"2022-12-15T17:48:43","guid":{"rendered":"https:\/\/labs.uthscsa.edu\/ma\/?page_id=107"},"modified":"2026-01-02T03:42:40","modified_gmt":"2026-01-02T03:42:40","slug":"project","status":"publish","type":"page","link":"https:\/\/labs.uthscsa.edu\/ma\/project\/","title":{"rendered":"Project"},"content":{"rendered":"

[vc_row el_class=”roomy” css=”.vc_custom_1691528487356{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_column_text]<\/p>\n

Projects background\u00a0<\/strong><\/h2>\n

[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”173″ img_size=”full” add_caption=”yes” onclick=”img_link_large” img_link_target=”_blank” css_animation=”fadeIn” css=”.vc_custom_1737320004117{margin-left: 50px !important;}” title=”Project – SNX19 in schizophrenia and Alzheimer’s disease”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1737321028131{margin-right: 50px !important;margin-left: 50px !important;}”]Based on schizophrenia GWAS data, we discovered a specific cluster of SNX19 gene transcripts associated with schizophrenia risk using RNA-seq and DNA methylation data combined with the genotyping data generated from 495 postmortem brains of schizophrenia and controls. We also investigated SNX19 transcript patterns in autopsy brains through molecular and cell biology experiments (Ma et al. 2020<\/a>).<\/p>\n

We are using CRISPR gene editing on human induced pluripotent stem cells (hiPSCs) to create isogenic lines, followed by differentiating them into 2D neurons and 3D brain organoids to study the impact of SNX19 on neuronal function (e.g., synapse loss, calcium level, and autophagy).\u00a0We are performing a series of behavior tests in mouse model to investigate the impact of SNX19 on cognitive functions.<\/p>\n

This work is funded by NIH and the Alzheimer’s Association.[\/vc_column_text][\/vc_column][\/vc_row][vc_row css=”.vc_custom_1691528501740{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_separator border_width=”2″][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”169″ img_size=”full” onclick=”img_link_large” img_link_target=”_blank” css_animation=”fadeIn” css=”.vc_custom_1737319982478{margin-left: 50px !important;}” title=”Project – CYP2D6 in schizophrenia”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1737320852992{margin-right: 50px !important;margin-left: 50px !important;}”]I extended the investigation of functional genomic regions of schizophrenia from one gene to the whole genome to analyze RNA-seq data from 1,479 human postmortem brains combined with their whole-genome sequencing data. While confirming SNX19 splicing events in schizophrenia risk, I also identified alternative transcripts of CYP2D6 predisposed to schizophrenia. In parallel, I determined causal variations of CYP2D6 transcription by ChIP-seq and DNA methylation data generated from another cohort of human postmortem brains. Finally, convergence upon CYP2D6 as an essential candidate gene was identified again using a data-driven enrichment analysis (Ma et al. 2021<\/a>).\u00a0We are investigating the role of CYP2D6 in brain using the mouse model and human iPSC-derived models.[\/vc_column_text][\/vc_column][\/vc_row][vc_row css=”.vc_custom_1691528501740{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_row_inner][vc_column_inner width=”1\/2″][vc_single_image image=”278″ img_size=”full” css=”” title=”Project – APOE in Alzheimer’s disease”][\/vc_column_inner][vc_column_inner width=”1\/2″][vc_column_text css=””]APOE4 is the strongest genetic risk factor in Alzheimer\u2019s disease. However, just having APOE4 doesn\u2019t mean someone will definitely develop Alzheimer\u2019s, and not having it doesn\u2019t eliminate the risk either.<\/p>\n

Recent large-scale genetic studies have uncovered additional variations in the APOE region. These variations have been linked to Alzheimer\u2019s risk, but the challenge has been figuring out which APOE mRNA these variations affect in the brain.<\/p>\n

To explore this further, we analyzed brain data from deceased individuals. For the first time, we discovered a specific version of the APOE gene, called the jxn1.2.2 transcript, that may increase Alzheimer\u2019s risk in people of European and African ancestry, regardless of their APOE2, APOE3, or APOE4 type.<\/p>\n

This work has been published on Molecular Neurodegeneration<\/a> and is supported by the Alzheimer’s Association and the National Alzheimer\u2019s Coordinating Center New Investigator Award (NIAP<\/a>). We are leveraging CRISPR genome editing using human iPSC-derived models to study the risk factors we identified.[\/vc_column_text][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”313″ img_size=”full” css=”” title=”Project – Cell2Spatial”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=””]Cell2Spatial: Reconstructing Tissue Architecture at Single-Cell Granularity to map single-cell data onto spatial transcriptomic spots (Li et al. 2025 PLOS Biology<\/a>).[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text css=””]<\/p>\n

Ongoing Project<\/strong><\/h2>\n

[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”174″ img_size=”full” css=”.vc_custom_1691700153690{margin-left: 50px !important;}” title=”Genome-wide study”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1691701904399{margin-right: 50px !important;margin-left: 50px !important;}”] <\/p>\n

 <\/p>\n

We perform genome-wide association between genetic variants and gene expression features, DNA methylations, histone markers, and more.[\/vc_column_text][\/vc_column][\/vc_row][vc_row css=”.vc_custom_1691528501740{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_separator border_width=”2″][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”175″ img_size=”full” css=”.vc_custom_1691700191805{margin-left: 50px !important;}” title=”Transcripts diversity”][vc_single_image image=”176″ img_size=”full” css=”.vc_custom_1691700219003{margin-left: 50px !important;}” title=”Epigenetic markers”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1691701750555{margin-right: 50px !important;margin-left: 50px !important;}”] <\/p>\n

 <\/p>\n

We are combing short-read RNA-seq and long-read sequencing to decipher transcript expression patterns in human brains.[\/vc_column_text][vc_column_text css=”.vc_custom_1691701775858{margin-right: 50px !important;margin-left: 50px !important;}”] <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

We use DNA methylation, ChIP-seq, and ATAC-seq to study the gene regulatory mechanisms.[\/vc_column_text][\/vc_column][\/vc_row][vc_row css=”.vc_custom_1691528501740{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_separator border_width=”2″][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”179″ img_size=”full” css=”.vc_custom_1691700241257{margin-left: 50px !important;}” title=”CRISPR gene editing”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1691701590976{margin-right: 50px !important;margin-left: 50px !important;}”] <\/p>\n

 <\/p>\n

We are using CRISPR editing technology (Ran et al. 2013 Nat Protoc<\/a>) on the disease genes we prioritized (e.g., SNX19).[\/vc_column_text][\/vc_column][\/vc_row][vc_row css=”.vc_custom_1691528501740{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_separator border_width=”2″][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”177″ img_size=”full” onclick=”img_link_large” css=”.vc_custom_1691700270257{margin-left: 50px !important;}” title=”Generating neuronal cells from human iPSCs”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1691701559386{margin-right: 50px !important;margin-left: 50px !important;}”] <\/p>\n

 <\/p>\n

 <\/p>\n

The Application of iPS Cells and Differentiated Neuronal Cells To Advance Drug Discovery<\/a>[\/vc_column_text][\/vc_column][\/vc_row][vc_row css=”.vc_custom_1691528501740{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_separator][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”178″ img_size=”full” onclick=”img_link_large” css=”.vc_custom_1691700296643{margin-left: 50px !important;}” title=”Modeling brain disease using organoids”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1691701515798{margin-right: 50px !important;margin-left: 50px !important;}”] <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

Figure legend:<\/p>\n

A brain organoid<\/a> showing neuron precursors (magenta) and deep-layer projection neurons (green).[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column][vc_separator color=”green” css=””][\/vc_column][\/vc_row][vc_row][vc_column][vc_column_text css=””]Funding Agencies<\/a><\/strong>[\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/3″][vc_single_image image=”279″ img_size=”full” css=””][\/vc_column][vc_column width=”1\/3″][vc_single_image image=”281″ img_size=”full” css=””][\/vc_column][vc_column width=”1\/3″][vc_single_image image=”280″ img_size=”full” css=””][\/vc_column][\/vc_row]<\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

[vc_row el_class=”roomy” css=”.vc_custom_1691528487356{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_column_text] Projects background\u00a0 [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”173″ img_size=”full” add_caption=”yes” onclick=”img_link_large” img_link_target=”_blank” css_animation=”fadeIn” css=”.vc_custom_1737320004117{margin-left: 50px !important;}” title=”Project – SNX19 in schizophrenia and Alzheimer’s disease”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1737321028131{margin-right: 50px !important;margin-left: 50px !important;}”]Based on schizophrenia GWAS data, we discovered a specific cluster of SNX19 gene transcripts associated with schizophrenia risk using RNA-seq and DNA […]<\/p>\n","protected":false},"author":76,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-templates\/no-banner.php","meta":{"footnotes":""},"class_list":["post-107","page","type-page","status-publish","hentry"],"yoast_head":"\nProject - Liang Ma Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/labs.uthscsa.edu\/ma\/project\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Project - Liang Ma Lab\" \/>\n<meta property=\"og:description\" content=\"[vc_row el_class=”roomy” css=”.vc_custom_1691528487356{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_column_text] Projects background\u00a0 [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”173″ img_size=”full” add_caption=”yes” onclick=”img_link_large” img_link_target=”_blank” css_animation=”fadeIn” css=”.vc_custom_1737320004117{margin-left: 50px !important;}” title=”Project – SNX19 in schizophrenia and Alzheimer’s disease”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1737321028131{margin-right: 50px !important;margin-left: 50px !important;}”]Based on schizophrenia GWAS data, we discovered a specific cluster of SNX19 gene transcripts associated with schizophrenia risk using RNA-seq and DNA […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/labs.uthscsa.edu\/ma\/project\/\" \/>\n<meta property=\"og:site_name\" content=\"Liang Ma Lab\" \/>\n<meta property=\"article:modified_time\" content=\"2026-01-02T03:42:40+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/project\\\/\",\"url\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/project\\\/\",\"name\":\"Project - Liang Ma Lab\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/#website\"},\"datePublished\":\"2022-12-15T17:48:43+00:00\",\"dateModified\":\"2026-01-02T03:42:40+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/project\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/project\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/project\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Project\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/#website\",\"url\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/\",\"name\":\"Liang Ma Lab\",\"description\":\"Liang Ma Lab\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/labs.uthscsa.edu\\\/ma\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Project - Liang Ma Lab","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/labs.uthscsa.edu\/ma\/project\/","og_locale":"en_US","og_type":"article","og_title":"Project - Liang Ma Lab","og_description":"[vc_row el_class=”roomy” css=”.vc_custom_1691528487356{margin-right: 50px !important;margin-left: 50px !important;}”][vc_column][vc_column_text] Projects background\u00a0 [\/vc_column_text][\/vc_column][\/vc_row][vc_row][vc_column width=”1\/2″][vc_single_image image=”173″ img_size=”full” add_caption=”yes” onclick=”img_link_large” img_link_target=”_blank” css_animation=”fadeIn” css=”.vc_custom_1737320004117{margin-left: 50px !important;}” title=”Project – SNX19 in schizophrenia and Alzheimer’s disease”][\/vc_column][vc_column width=”1\/2″][vc_column_text css=”.vc_custom_1737321028131{margin-right: 50px !important;margin-left: 50px !important;}”]Based on schizophrenia GWAS data, we discovered a specific cluster of SNX19 gene transcripts associated with schizophrenia risk using RNA-seq and DNA […]","og_url":"https:\/\/labs.uthscsa.edu\/ma\/project\/","og_site_name":"Liang Ma Lab","article_modified_time":"2026-01-02T03:42:40+00:00","twitter_card":"summary_large_image","twitter_misc":{"Est. reading time":"6 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/labs.uthscsa.edu\/ma\/project\/","url":"https:\/\/labs.uthscsa.edu\/ma\/project\/","name":"Project - Liang Ma Lab","isPartOf":{"@id":"https:\/\/labs.uthscsa.edu\/ma\/#website"},"datePublished":"2022-12-15T17:48:43+00:00","dateModified":"2026-01-02T03:42:40+00:00","breadcrumb":{"@id":"https:\/\/labs.uthscsa.edu\/ma\/project\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/labs.uthscsa.edu\/ma\/project\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/labs.uthscsa.edu\/ma\/project\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/labs.uthscsa.edu\/ma\/"},{"@type":"ListItem","position":2,"name":"Project"}]},{"@type":"WebSite","@id":"https:\/\/labs.uthscsa.edu\/ma\/#website","url":"https:\/\/labs.uthscsa.edu\/ma\/","name":"Liang Ma Lab","description":"Liang Ma Lab","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/labs.uthscsa.edu\/ma\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"}]}},"_links":{"self":[{"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/pages\/107","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/users\/76"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/comments?post=107"}],"version-history":[{"count":0,"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/pages\/107\/revisions"}],"wp:attachment":[{"href":"https:\/\/labs.uthscsa.edu\/ma\/wp-json\/wp\/v2\/media?parent=107"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}