Sumaira Hasnain

Disrupting Immune Responses to Reverse Fibrosis

Biomedical and clinical sciences

Project description

Intestinal fibrosis is a debilitating complication affecting a significant portion of patients with Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn's Disease (CD). Chronic inflammation within the intestinal tract leads to excessive collagen production by fibroblasts, resulting in luminal narrowing, obstruction, and a significant decline in quality of life.

Recent studies have suggested a potential role for interleukin-24 (IL-24) in the pathogenesis of IBD. IL-24 is a cytokine with both pro-inflammatory and anti-inflammatory properties, and it has been implicated in various fibrotic diseases.

This research aims to investigate the specific role of IL-24 in driving intestinal fibrosis in IBD, with a particular focus on its ability to activate transforming growth factor-beta (TGF-beta), a key mediator of fibrosis.

Specific Research Questions:

1. Expression of IL-24 and TGF-beta in fibrotic intestinal tissue: Are IL-24 and TGF-beta upregulated in fibrotic regions of the intestine in IBD patients?
2. IL-24-mediated activation of TGF-beta: Does IL-24 directly or indirectly stimulate the production and activation of TGF-beta in intestinal fibroblasts?
3. Role of TGF-beta in IL-24-induced fibrosis: What are the downstream effects of TGF-beta activation in promoting intestinal fibrosis?
4. Therapeutic potential of targeting IL-24 or TGF-beta: Can inhibiting IL-24 or TGF-beta pathways be a potential therapeutic strategy for preventing or treating intestinal fibrosis in IBD?

The Link Between Cellular Stress and Antigen Presentation

The endoplasmic reticulum (ER) plays a crucial role in the production and presentation of MHC Class II antigens, which are essential for the immune system to recognize and eliminate foreign invaders. When proteins are misfolded or improperly assembled in the ER, it can trigger a cellular stress response known as ER stress. This stress can impact the generation and presentation of MHC Class II antigens in several ways. Our focus has been on antigen presentation by nonprofessional antigen presenting cells like epithelial cells. Project Aim: To investigate the complex relationship between protein misfolding, ER stress, and MHC Class II antigen presentation, with a focus on understanding how these factors influence the development of immune responses, particularly those involving CD4+ T cells. Expected outcomes and deliverables: This project will be undertaken at UQ (Mater Research Institute) within the Translational Research Institute (TRI) which is a collaborative building that incorporates over 1200 research scientists and students. TRI also provides an exceptional research environment with access to state-of-art facilities including flow cytometry, microscopy and a strong network of research support professionals. There is support for PhD students, through UQ as well as Mater Student Committee (sMater). The honours student will learn a range of techniques, in particular, flow cytometry, histology, Confocal Microscopy and preclinical animal work. There is a potential of extending the honours project into a PhD project.

Decoding the IL-22RA1-Insulin Biosynthesis Link: A New Target for Diabetes

The IL-22RA1 receptor is abundant in the pancreas, and external IL-22 has been shown to improve pancreatic islet health and insulin secretion. However, the natural function of IL-22RA1 signalling within these cells is incompletely understood. Our recent work has shown that endogenous IL-22RA1 signalling in regulating insulin secretion, islet regeneration, and overall metabolic health. Understanding the specific mechanisms involved in IL-22RA1-mediated regulation of pancreatic beta cell function could lead to novel therapeutic strategies for diabetes and other metabolic disorders. This project will focus on investigating the exact mechanisms by which IL-22 regulates these processes, with a particular focus on calcium storage and cytoskeletal changes. Expected outcomes and deliverables: This project will be undertaken at UQ (Mater Research Institute) within the Translational Research Institute (TRI) which is a collaborative building that incorporates over 1200 research scientists and students. TRI also provides an exceptional research environment with access to state-of-art facilities including flow cytometry, microscopy and a strong network of research support professionals. There is support for PhD students, through UQ as well as Mater Student Committee (sMater). The honours student will learn a range of techniques, in particular, flow cytometry, histology, Confocal Microscopy and preclinical animal work. There is a potential of extending the honours project into a PhD project.