Information détaillée

• Retourner à l'interrogation

Titre du projet :

Unravelling the Cellular and Immunologic Landscape of the Gut in Children with Primary Sclerosing Cholangitis at Single-Cell Resolution

Chercheur principal :

Ricciuto, Amanda; Bader, Gary D; MacParland, Sonya

Co-chercheurs :

Erdman, Lauren; Mortha, Arthur; SIDDIQUI, IRAM; Vyas, Mary P; Walters, Thomas D

Directeur(s) de recherche :

S/O

Établisssement payé :

Hospital for Sick Children (Toronto)

Établissement de recherche :

Hospital for Sick Children (Toronto)

Département :

S/O

Programme :

Subvention Projet

Concours (année/mois) :

202409

CEP désigné :

Investigation clinique - C : Systèmes digestif, endocrinien et excrétoire

Institut principal :

Nutrition, métabolisme et diabète

Thème principal :

Recherche clinique

Durée (année/mois) :

4 ans 0 mois

Contribution des IRSC :

Donateurs :

Montant :

822 376$

Équipement :

0$

Contribution du partenaire externe :

Nom du partenaire :

S/O

Montant :

S/O

Équipement :

S/O

Partenaire du candidat à l'externe :

Nom du partenaire :

S/O

Montant :

S/O

Équipement :

S/O

Partenaire externe (en nature) :

Nom du partenaire :

S/O

Montant :

S/O

Équipement :

S/O

Mots clés :

Colitis; Inflammatory Bowel Disease (Ibd); Machine Learning; Paediatric; Primary Sclerosing Cholangitis (Psc); Screening; Single-Cell Transcriptomics

Résumé :

Primary sclerosing cholangitis (PSC) is a progressive autoimmune liver disease that causes people's bile ducts (tubes that drain bile from the liver) to scar down. This often leads to liver failure (needing a liver transplant) or death due to bile duct cancer or colon cancer. Most people with PSC also have inflammatory bowel disease (chronic inflammation in their large bowel or colon). We call this PSC-IBD. In the past, researchers thought PSC-IBD was just the coexistence of 2 diseases (PSC and IBD). However, there is more and more evidence to suggest that PSC-IBD is probably due to a single underlying disease process that affects both the liver and gut. Despite the likely important role of the gut in patients with PSC, the gut has not yet been carefully studied. In Aim 1, we will deeply characterize the cells making up the gut in children with PSC using a technique called single-cell RNA sequencing (scRNA-seq). This tells us the genes being expressed by each cell (i.e., tells us which genes are "on" in each cell), which allows very detailed mapping of the cells in the gut and their functions. We will compare this "map" to maps from children who have IBD (without PSC) and to children who do not have inflammation in their bowel. In Aim 2, we will analyze samples collected 6-12 months later. We will look at changes in scRNA-seq over time compared to changes in gut inflammation measured by a doctor examining samples under the microscope. This will specifically tell us about which cells and processes are important to causing inflammation in the gut of PSC patients (and how this compares to children with IBD without PSC). Finally, in Aim 3, we will use our findings to build a classifier (a tool) that helps to tell PSC-IBD and non-PSC IBD apart. This will be an important first step toward developing a screening test that can pick up PSC in people with IBD.

• Retourner à l'interrogation

Version :

20250311.1