Trainee Projects

Under the supervision of Dr. Mia Biondi, I am conducting a research project titled Developing the Fibrosis Field Score: A Clinical Assessment Tool for Estimating Liver Fibrosis Progression in Chronic Hepatitis C Without Laboratory Testing. Although hepatitis C treatment is universally funded in Canada, major structural and geographic barriers limit access to care. Current international guidelines require an assessment for advanced liver disease prior to initiating treatment, which often entails multiple appointments and blood draws. While serum biomarkers have made this process more accessible than liver biopsy or fibroscan, the need for repeated visits still leads to high rates of loss to follow-up. This is especially challenging for people who use drugs, as phlebotomy can be difficult due to poor venous access and limited ability to attend laboratory appointments. Moreover, reliance on lab-based assessments restricts the integration of hepatitis C care into peer-led or low-barrier outreach models—despite their demonstrated success in engaging high-risk populations.  

Our study aims to address these challenges by developing a non-invasive, history-based tool to estimate the likelihood of advanced liver fibrosis using clinical and demographic data alone. Building on prior research that has identified predictors such as age, substance use, BMI, sex, and alcohol use, we will use the Canadian Network Undertaking against Hepatitis C (CANUHC) dataset to develop and validate this tool.  

The fibrosis field score has the potential to streamline care pathways, expand treatment access, and support Canada's efforts to eliminate hepatitis C—particularly among underserved populations!  

My research looks at how Hepatitis C virus (HCV) affects people with HIV (PWH), especially how it helps HIV stay hidden in the body even during treatment. HIV treatment, called antiretroviral therapy (ART), can stop the virus from growing, but it doesn’t remove it completely. That’s because HIV hides in special immune cells called memory CD4+ T-cells. These cells "remember" past infections and can carry hidden HIV, forming what are called HIV reservoirs.

I had two main questions: “Does having HCV infection make CD4+ T-cells more vulnerable to HIV? and what happens to HIV reservoirs after HCV is cured with direct-acting antivirals (DAAs)?” My work also investigates whether CD4+ T-cells that respond to HCV can also carry HIV and act as long-term reservoirs. Interestingly, my research revealed that after curing HCV with DAAs, the amount of HIV in the body dropped, and inflammation also got better—but HIV wasn’t fully gone.  

The results I generated so far add to the understanding of the interplay between HCV and HIV in fueling HIV pathogenesis and limiting the chances for HIV cure. These findings raise awareness of the urgent need to treat HCV infection early in PWH to help reduce HIV reservoirs and support efforts toward finding a cure for both viruses. 

In the Sagan Lab at UBC we are really interested in the host-virus interactions important in the hepatitis C virus (HCV) life cycle. Of particular interest to us is the process of viral RNA replication, which occurs on altered host cell membranes. During infection, the virus induces dramatic remodelling of the host cell endoplasmic reticulum (ER). This leads to the formation of a membranous web, primarily composed of double membrane vesicles derived from the ER. These DMVs are known as replication organelles (ROs) and are the sites of viral RNA replication during infection. RNA replication proceeds through a negative-strand intermediate RNA, which is then used as a template for the subsequent synthesis of new genomic viral RNAs. While there is some evidence suggesting that ROs contain a single-copy of the negative-strand RNA, there is no direct evidence of this during HCV infection. My research uses single-molecule imaging of HCV RNAs during infection to quantify the number of negative-strands in each RO. Additionally, my imaging workflow allows me to quantify other aspects of the viral life cycle including RNA accumulation and subcellular localization dynamics. My research will help to improve our understanding of the viral life cycle and may illuminate novel strategies for anti-viral interventions.  Additionally, my results are likely applicable to other RNA viruses, which include a number of important human pathogens.  

Despite the availability of effective treatments, the Hepatitis C virus (HCV) continues to pose a significant challenge, causing substantial harm and leading to severe health consequences such as cirrhosis, liver failure, and cancer. The advanced complications of the liver often seen in individuals actively battling HCV, as well as those who have been treated with direct-acting antivirals (DAAs), are frequently associated with dysregulated immune responses, complicating the overall disease landscape.

In our laboratory, we are dedicated to unravelling the complex mechanisms that contribute to immune dysfunction in chronic HCV infections. Our primary focus is to understand how this dysfunction impacts the progression of fibrosis and facilitates the development of liver cancer.

The liver contains the highest concentration of macrophages in any organ, serving as vital guardians of immune health. In cases of chronic injury, there is a significant influx of peripheral monocytes, which expands the macrophage population. Our research shows that macrophages derived from these peripheral monocytes, especially in the context of advanced liver fibrosis, exhibit pronounced inflammatory profiles and undergo changes in polarization. This disruption in their regulatory functions may undermine the liver's natural protective responses, worsening liver injury and leading to detrimental clinical outcomes.

By exploring the complex mechanisms underlying the dysfunction of these monocyte-derived macrophages, we aim to uncover critical insights that could lead to the development of innovative immunotherapeutic strategies. These strategies are intended to support patients dealing with established liver disease following HCV treatment, offering hope for improved health and well-being. We are optimistic that these findings may also apply to other similar fibrotic liver conditions, such as metabolic-associated fatty liver disease. 

Hepatitis C Virus (HCV) hacks liver cells and uses the cell’s machinery and resources to replicate. In doing so, viral components interact with cellular components to reprogram the cell into producing more virus and to evade recognition by innate immune sensors. In virology, the study of virus-host interactions is highly relevant to understand how the virus hijacks the cell, how it evades detection, and how it ultimately causes disease. By understanding these processes, we can develop strategies that target the virus itself or the cellular components it relies on—thereby finding a cure or viable treatment.

Direct-acting antivirals (DAAs) are effective drugs that directly target viral components and prevent disease. However, they do not prevent reinfection, nor do they reverse the liver damage caused by chronic (long-term) HCV infection. They also do not prevent the development of hepatocellular carcinoma. Therefore, understanding virus-host interactions during HCV infection remains essential.

Cyclophilin A (CypA) is a protein expressed by our cells that, under normal conditions, aids in the proper folding of other proteins. Interestingly, growing evidence suggests that CypA is essential for HCV replication. Studies have shown that when CypA function is inhibited by a drug—or entirely removed from the cell—HCV cannot replicate. My research partly focuses on further understanding CypA’s role in HCV infection.

Another interesting cell factor is protein kinase R (PKR), a double-stranded RNA sensor that upon activation, induces the interruption of protein synthesis and therefore also the production of viral proteins.

Moreover, PKR also activates transcription factors needed to mount an antiviral response. Notably, despite PKR having an antiviral role, it is highly activated during HCV infection both in vitro and in vivo, and in HCV-derived hepatocellular carcinoma surrounding tissue.   Studying these effects could help us better understand the mechanisms of disease and develop strategies to prevent liver damage and disease progression in HCV patients.

I am working with my supervisor, Dr. Mia Biondi, on a project called Hepatitis C Treatment During Pregnancy and Postpartum: A Qualitative and Prospective Observational Cohort Study. We're focused on improving care for pregnant women living with hepatitis C (HCV), especially those from marginalized communities who face barriers like substance use, limited healthcare access, and stigma. Although the Society of Obstetricians and Gynaecologists of Canada (SOGC) now recommends routine HCV screening in pregnancy, most women are only offered treatment after giving birth. Unfortunately, many do not follow up due to fear of judgment, lack of support, and competing priorities.

Our study explores offering HCV treatment during pregnancy—a time of increased healthcare engagement—which could cure the infection and prevent transmission to the baby. Using interpretive description methodology, we are investigating the research question: “In what ways do women with active hepatitis C infection explain their decision-making processes around accepting or declining HCV treatment during pregnancy and the postpartum period?”  

To answer this, we are conducting qualitative interviews with women during pregnancy and again six months postpartum to understand their motives and decision-making around treatment. Our goal is to create better care pathways and inform policy to support timely, effective care for both mothers and their children, ultimately contributing to the elimination of hepatitis C by increasing screening, treatment uptake, and preventing vertical transmission. 

Hepatitis C virus (HCV) affects over 50 million people worldwide and can lead to chronic liver disease, cirrhosis, and liver cancer. While antiviral treatments can cure HCV, reinfection remains a public health risk, and there is still no vaccine. This remains a major barrier to global HCV elimination.

My research focuses on understanding how the immune system naturally controls HCV, with the goal of uncovering insights that could inform vaccine development. Specifically, I study people who were previously infected with HCV, cleared the virus, and were later reinfected. Interestingly, many of these individuals are able to clear the virus again, which suggests that protective immunity is possible.

To investigate this, I use advanced single-cell technologies to analyze how the immune system, particularly CD8 T cells, responds during reinfection. By studying their gene expression, function, and metabolism, I aim to identify what distinguishes effective immune responses from those that fail to control the virus. These insights could help define what protective immunity looks like, which is a crucial step toward guiding the design of an effective HCV vaccine.

On World Hepatitis Day, I am proud to contribute to the growing body of research working toward a world free of hepatitis C. 

The discovery and administration of highly effective direct-acting antiviral therapy can offer a cure for Hepatitis C virus (HCV) infection. However, there is still much to be learned about the HCV biology and how this virus interacts with proteins and RNA within the liver cells it infects. In the lab of Dr. Selena Sagan, our work investigates the unique and complex structures the HCV viral RNA genome forms when it enters the cell and establishes an infection. Specifically, we investigate HCV’s interaction with a liver-specific microRNA (miRNA), called miRNA-122 (mir-122). miR-122’s interaction with the viral genome helps promote a successful viral infection, and we are continuing to investigate the precise mechanisms by which this occurs. We are also exploring how the HCV viral RNA interacts with specific viral and human proteins which aid in a successful infection. By understanding the complex interactions of viral proteins, human proteins, and miR-122 with the HCV RNA, we can begin to develop a better understanding behind how HCV establishes an infection. Furthermore, our research can provide insights into some potentially new antiviral therapies and even provide insights into a potential vaccine design that can aid in the elimination of HCV for good. 

In order to potentially eliminate a pathogen, it is important to understand how the pathogen works, specifically how it interacts with our cells to cause infection. My research is focused on how hepatitis C virus interacts with its host to cause infection and if we can use these interactions to learn more about both viral and cell biology.  Fortunately, we are in an era where direct acting antivirals (DAAs) are highly effective at curing individuals infected with HCV. However, the use of DAAs does not eliminate the long-term risks associated with chronic HCV infection. Therefore, understanding how HCV causes infection could provide insight into how we may reverse some of these lasting consequences.  

Particularly, I am interested in understanding how HCV (and other related viruses) interacts with a cellular organelle called the endoplasmic reticulum (ER). The ER is a hub for protein synthesis within our cells, which provides our cells with the necessary resources to function. Many viruses, including HCV can hijack these factories to support their replication, which in turn causes a strain on the ER, leading to ER stress. ER stress can activate antiviral responses; thus, we speculate that HCV may have mechanisms to counteract this stress to promote viral infection.

By investigating how HCV manipulates ER stress responses, we can gain valuable knowledge that could inform novel host-targeted antiviral strategies for HCV and other viruses that manipulate the ER. 

When we talk about hepatitis C (HCV) elimination, we often jump straight into statistics, diagnostics, and treatment targets. But my work in Montreal’s needle and syringe programs has taught me something simple but powerful: elimination starts with trust. People who inject drugs, one of the populations most affected by hepatitis C; don’t just need access to testing; they need care they can trust. That means creating low-barrier spaces where point-of-care testing (POCT) doesn’t feel like another institutional touchpoint, but like a bridge toward dignity and health.

Implementing HCV POCT in harm reduction settings isn’t just a logistical challenge, it’s a human one. Trust isn’t something you install. It’s something you co-create over time, by being present, consistent, and willing to adapt your strategies to community realities. That’s what our project is about: mapping what’s already working, identifying where the gaps are, and co-designing with people, not just for them.

That’s why co-design isn’t a buzzword. It’s a method of survival.

When we invite frontline workers and people who use drugs to co-design the implementation blueprint for HCV POCT, we are not being generous, we are being realistic. No amount of evidence can substitute for lived experience and expertise. The “right” intervention, if done without community voices, will still miss the mark. Co-design helps us avoid that pitfall. It helps ensure our strategies are not only evidence-informed but context-grounded and culturally safe. It has been reported that systems of care have not always been safe or inclusive for people who use drugs. Co-design becomes a way to repair relationships, share power, and build buy-in. For hepatitis C elimination to be more than a policy goal, it must be a practice of inclusion, from start to finish.

So what does elimination look like: It isn’t just a line graph trending down. It’s the moment a client says yes to a test they once refused. It’s the outreach worker who now carries a POCT kit in their backpack. It’s the site that went from sending samples to central labs to getting results in minutes.

For me, elimination looks like integration. It means embedding care into systems people already trust, places where they feel safe, seen, and respected. It also looks like humility. We are not dropping solutions from above. Rather, we are learning alongside those most affected. That’s the heart of implementation research. And that’s the path we are walking together.

Chronic hepatitis B (lifelong infection) affects millions worldwide, leading to serious complications like liver cirrhosis and cancer. Although we have effective vaccines and treatments to suppress the virus, there is still no cure, and most chronic cases start with infection at birth. I am working with my supervisor, Dr. Carla Coffin, to investigate why babies and young children are much more likely to develop chronic hepatitis B than adults. Does the interaction between the gut microbiome and the immune system influence the persistence of hepatitis B virus (HBV) infection?

My research uses a very valuable animal model, the woodchuck (groundhog), which closely mimics human HBV infection. We aimed to study the differences in gut microbiome composition and immune responses between young and adult animals. By comparing these groups and examining the effects of antiviral treatment, I hope to identify how the gut microbiome might affect the immune system’s ability to clear the virus. Recent evidence suggests that the maturation of gut microbiota in adults helps stimulate liver immunity and promote HBV clearance, while immature microbiomes in the young may foster immune tolerance and chronic infection.

This research could lead to innovative strategies for HBV cure and support global efforts to eliminate hepatitis as a public health threat by 2030. 

Chronic hepatitis damages more than just the liver: over time, cells of the immune system also become impaired. My research studies a particular type of immune cell called T cells. These are cells that specialize in fighting viruses (such as HCV) and cancers (such as liver cancer). Properly functioning T cells also help vaccines induce a strong protective effect. Unfortunately, T cells that were damaged by chronic hepatitis remain damaged even after curing the HCV infection itself, meaning that people with previous chronic hepatitis often remain stuck with a vulnerable immune system, despite having a completely healed liver.

More specifically, my research tries to uncover why some T cells become abnormally active in people with advanced stages of chronic liver damage. T cells that specifically target the HCV virus are known to become less active during chronic infections, yet our team has observed that the majority of other T cells become abnormally over-active. This over-activity of T cells that are not supposed to respond to HCV itself seem to be caused, at least in part, by an abnormally active metabolism inside the cells, likely induced by the long-lasting inflammatory environment of the damaged liver. Over time, these over-active cells end up losing their ability to properly focus their fight on their intended target viruses or cancers, leaving the immune system vulnerable even after healing the liver.

We hope that by fully understanding the dynamics between liver damage and immune cells, new treatments will become possible to help restore proper immune function for those recovering from all forms of chronic liver disease.