2025 Grant Awards

Announcing Our 2025 PSC Research Grant Awardees

We’re proud to unveil the five outstanding research projects selected for funding through the 2025 grant cycle. This year, PSC Partners Seeking a Cure awarded four grants—including two Young Investigator Awards and two Standard Seed Grants—and PSC Partners Seeking a Cure Canada awarded one Standard Grant. These competitive awards reflect our ongoing commitment to advancing PSC research and supporting the next generation of scientists.

A Record Year for Research Interest
This year, interest in PSC research was stronger than ever. We received:

• 43 Letters of Intent
• 38 full applications, including 26 preclinical and 12 clinical projects

Of these applications:

• 17 were eligible for Standard Seed Grant funding
• 21 qualified for Young Investigator Award consideration

Aligned with Our Research Priorities
We are encouraged that many of the submissions aligned with PSC Partners' key research priorities:

• 25 projects focused on improving understanding of the mechanisms contributing to PSC development and progression
• 16 explored the gut-liver connection in PSC and PSC-IBD
• 17 aimed to develop safe and effective treatments to slow disease progression and reduce symptom burden
• 9 addressed early detection and treatment of PSC-related cholangiocarcinoma

Many projects addressed multiple research priorities, highlighting the complexity of PSC and the multidisciplinary approach required to tackle it.

A Rigorous and Inclusive Review Process
Each application underwent a highly competitive and rigorous review process. Projects were carefully evaluated by our Scientific/Medical Advisory Committee (SMAC)—a panel of leading PSC researchers and clinicians. Projects selected for funding by PSC Partners Seeking a Cure were additionally reviewed by the PSC Partners Community Review Committee, which includes patients, caregivers, and family members.

Explore the 2025 grant recipients below and discover how their innovative research is advancing our understanding of PSC

Modulation of Hepatic Macrophage Differentiation and Efferocytosis by Propionate to Ameliorate Fibrosis

Principal Investigator: Olumuyiwa Awoniyi, Cleveland Clinic Foundation

AWARD: $100,000 over two years (Young Investigator Award)

Project Summary: Primary sclerosing cholangitis (PSC) is a progressive liver disease with no effective therapies to halt its progression. Emerging evidence suggests that gut microbes producing short-chain fatty acids (SCFAs) play a protective role in PSC by influencing liver macrophage function, which regulates liver inflammation and fibrosis. In the PSC mouse model (Mdr2-/-), we found that the SCFA propionate reduces fibrosis and promotes the differentiation of macrophages into a reparative phenotype that clears dying cells (efferocytosis), critical for reducing liver damage. This project investigates how propionate modulates macrophage function in PSC through two complementary aims: (1) identifying how propionate impacts macrophage differentiation and efferocytosis in PSC mice using genetic and biochemical tools, and (2) examining propionate's effects on macrophages in liver samples from PSC patients compared to controls. By uncovering how SCFAs like propionate regulate liver macrophages, this research could pave the way for novel PSC treatments targeting gut-liver interactions and inflammation. 

Exploring Mechanisms of PSC Progression with an In Vitro Bile Duct on a Chip

Principal Investigator: Henry Hoyle, University of Oslo 

AWARD: $100,000 over two years (Young Investigator Award)

Project Summary: Primary sclerosing cholangitis (PSC) is a debilitating disease in the liver which causes inflammation and structuring in the bile ducts. It has a significant burden on patients and currently has no medical treatments, leading eventually to liver failure and a need for transplant. A lack of effective preclinical models is one factor which is slowing the development of effective drugs to treat PSC. We have developed an advanced model of the bile duct which could allow us to study PSC in the lab. This model utilizes human biological material directly from patients and therefore provides a more human-relevant model compared to mouse models, which are currently the gold standard in the field. In this project we aim to incorporate further aspects of the biliary microenvironment, such as patient matched bile and immune cells, to create a broad recapitulation of PSC. We can then test drugs on the model targeting a variety of pathways to study the effects and see if the model can be effectively used to predict potential drug candidates for the treatment of PSC. It is hoped that with a successful in vitro model for studying PSC we can speed up the preclinical development of treatments and help to bring potential drugs closer to the clinic. 

Dissecting Unique Immunopathogenic Mechanisms in Primary Sclerosing Cholangitis (UnikPATH)

Principal Investigator: Xiaojun Jiang, Oslo University Hospital

AWARD: $75,000 over two years

Project Summary: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease that damages the bile duct and often leads to liver transplantation. Despite extensive evidence linking immune dysregulation to PSC, both traditional and newer treatments targeting these aspects have shown poor efficacy. This underscores the complexity of PSC bile duct inflammation and highlights the need for a deeper understanding of local disease-causing immune mechanisms. Our project aims to bridge this gap by investigating a putative disease-causing mutation, CD100 K849T, identified in a family with inherited PSC. While CD100 mutation is widely expressed on immune cells, it is specifically associated with PSC bile duct disease without resulting in widespread immune disorders. Thus, bile duct-specific tissue environment is likely to be required for the mutation's pathogenic effects to manifest. We expect to determine what are the tissue factors involved and to what extent related tissue-immune mechanisms contribute to biliary damage in boarder PSC cases. The insights gained from this study may pave the way for the development of more targeted and effective treatments for PSC, ultimately improving the quality of life for affected individuals. 

Characterizing the Cellular Microenvironment of the PSC Extrahepatic Bile Duct

Principal Investigator: Sonya MacParland, University Health Network

AWARD: $75,000 over two years

Project Summary: PSC is a rare autoimmune disease affecting bile ducts, leading to liver damage, cirrhosis, and cancer. While much is known about the liver and the small bile ducts, the large bile ducts outside the liver remain poorly studied. At the PSCP/ICRN 2024 meeting, the PSC community emphasized the need to investigate how large bile ducts are impacted by PSC compared to healthy and other liver diseases. This project directly addresses that need by studying large bile ducts from PSC, primary biliary cholangitis (PBC), and healthy donors collected at the time of transplantation. Using advanced single-cell and spatial transcriptomics, we will profile individual cells in large bile ducts to uncover PSC-specific changes. For each bile duct, we will also study matched liver and blood samples to link cellular changes across tissues. This comprehensive approach will reveal which immune cells are recruited to large bile ducts in PSC and how they differ from those in PBC or healthy controls. 

Elucidating Fatigue-Associated Alterations of Brain Structure and Function in PSC

Lead Investigator: Mark Swain, MD, MSc, University of Calgary

AWARD: $75,000 (Standard Seed Grant)

PSC patients often experience symptoms like fatigue, which significantly diminishes quality of life. PSC-associated fatigue is not improved by current IBD treatments and is independent of liver disease severity. Thus, new treatment approaches for PSC-related fatigue represent a highly patient-relevant, unmet medical need. Developing such treatments, however, requires a better understanding of what causes the symptoms. In recent studies in IBD patients without PSC, and in patients with a liver disease called primary biliary cholangitis that is impaired bile flow like PSC, we showed using magnetic resonance imaging (MRI) that there are changes in the size of some of the regions that regulate behavior, and how well these regions communicate with each other; these changes were linked to symptoms, including fatigue. We suggest similar brain changes drive the development of PSC-associated symptoms, like fatigue. In this proposal, we will advanced MRI techniques to determine the impact of PSC on brain structure and function, and how these change are linked to fatigue severity and activation of the bodies' immune system. This will help identify targets for therapy to improve fatigue in PSC patients.