Author Interviews, Gastrointestinal Disease, Hepatitis - Liver Disease / 13.05.2025
Role of Genetic Research in Advancing PSC Treatment
MedicalResearch.com discussion with:
Dr. Bertus Eksteen PhD, MBChB, FRCP
Founder of the Calgary PSC Clinic
Member of the Calgary Liver Unit and the Southern Alberta Liver Transplant Clinic
Aspen Woods Clinic
Calgary, Canada
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Dr. Bertus Eksteen[/caption]
Primary sclerosing cholangitis (PSC) is a liver disease characterized by progressive inflammation and scarring of the bile ducts. PSC still has no known cause or cure and often leads to liver failure or cancer. For patients and clinicians, the lack of answers is deeply frustrating. But that's beginning to change.
Thanks to genetic research, we’re uncovering clues about PSC’s origins—and why it behaves differently from patient to patient. By learning more about the genomic underpinnings of PSC, researchers can create new treatment targets, devise risk profiles for early diagnosis, and even develop better clinical tools for detecting the disease in its earliest stages.
And that path forward doesn’t just start with new treatments — it begins in the lab.
Dr. Bertus Eksteen[/caption]
Primary sclerosing cholangitis (PSC) is a liver disease characterized by progressive inflammation and scarring of the bile ducts. PSC still has no known cause or cure and often leads to liver failure or cancer. For patients and clinicians, the lack of answers is deeply frustrating. But that's beginning to change.
Thanks to genetic research, we’re uncovering clues about PSC’s origins—and why it behaves differently from patient to patient. By learning more about the genomic underpinnings of PSC, researchers can create new treatment targets, devise risk profiles for early diagnosis, and even develop better clinical tools for detecting the disease in its earliest stages.
And that path forward doesn’t just start with new treatments — it begins in the lab.
Dr. Steenson[/caption]
Dr. Simon Steenson PhD
Postdoctoral Research Associate
Department of Nutritional Sciences
King’s College London
MedicalResearch.com: What is the background for this study?
Response: Chronic constipation is something that can be embarrassing, but it affects 1 in 10 people globally. It has a big impact on people’s quality of life and treating constipation has substantial costs for the healthcare system. Dried fruits are recommended for managing constipation, but there are very few studies that have actually tested whether following this advice is helpful. To fill this gap in our knowledge, we completed the largest clinical trial to date to see whether dried fruits and fruit juices could benefit constipation symptoms.
Dr. Corley[/caption]
Douglas Corley, MD, PhD
Chief Research Officer, The Permanente Medical Group
Kaiser Permanente, Northern California
MedicalResearch.com: What is the background for this study?
Response: Kaiser Permanente Northern California (KPNC) is an integrated health care system that designs and implements population-based programs that support cancer prevention and early detection. In 2006, KPNC began to implement a comprehensive colorectal cancer screening program with the goal of increasing member screening rates, preventing colorectal cancer through polyp removal, and reducing cancer mortality. The initiative identifies whether screening-eligible KPNC members are up to date with their colorectal cancer screening test by either a colonoscopy or by stool-based tests, such as a fecal immunochemical testing (FIT) kit. If they are not up to date with screening, it mails them a FIT kit for at-home testing. Members can also choose other options for colorectal cancer screening, such as a colonoscopy, through their physician.
Shani Vaknine[/caption]
Shani Vaknine, Ph.D. candidate
Brain and Behavioral Sciences
The Hebrew University
MedicalResearch.com: What is the background for this study?
Response: We’ve long known that maternal stress during pregnancy can affect her baby’s development, but the molecular mechanisms behind this remained unclear. In our study, we explored how psychosocial stress experienced by the mother in late pregnancy influences tiny molecular fragments in the newborn’s blood. These fragments, called transfer RNA fragments or tRFs, were considered for many years to be disposable, but have recently been shown to have important biological functions.
Dr. Moyland[/caption]
Cynthia Moylan, MD
Associate Professor of Medicine,
Division of Gastroenterology
Duke University Health System
MedicalResearch.com: What is the background for this study?
Response: Metabolic dysfunction can lead to several health problems including metabolic dysfunction associated steatotic liver disease (MASLD), is driven by different factors, including: a person’s behavioral or lifestyle factors, environmental factors, and genetics. Limited research exists regarding genetic , epigenetic, or other factors that might impact development of metabolic dysfunction and MASLD. Our group has previously shown that alterations in DNA methylation (a type of epigenetic change), identifiable both in liver tissue and in blood, associate with MASLD and its progression to more severe liver disease. Whether DNA methylation that impacts imprinted gene expression also associates with metabolic dysfunction and MASLD risk remains largely unknown.
In this project, we explored imprinted genes: imprinting is a normal process that regulates genes by silencing one parental copy (either the maternal or the paternal) so that only one copy is expressed. Imprinting is an important biological process for development and has a disproportionate impact on disease - in fact, imprinted genes are hypothesized to affect 1-6% of the human genome. We sought to explore how altered DNA methylation of imprint control regions (ICRs) that help ‘control’ these imprinted genes might impact development of metabolic dysfunction in children (and hence potentially even in adults).
Luke Cavanah B.S.[/caption]
Luke Cavanah, BS
Department of Medical Education
Geisinger College of Health Sciences
Scranton, PA, 18509
MedicalResearch.com: What is the background for this study?
Response: Almost a third of patients with medication-treated major depressive disorder will fail at least two depressants—many patients failing more.1 Esketamine is an intranasal medication that was FDA-approved in 2019 for such patients when used in conjunction with an oral antidepressant.2 Esketamine also is unique from the more traditional oral antidepressants in its mechanism of action, quick onset, and evidence for treatment of acute suicidality.3 While esketamine has been of much interest for these last few years, a recent study found low and geographically variable use of this medication within the Medicaid population.4 We were interested in investigating esketamine treatment utilization among Medicare patients in 2019 and 2020.
Dr. Klonoff[/caption]
Dr. Zeynep Gümüş[/caption]
Zeynep H. Gümüş, PhD
Associate Professor
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: The germline genome of each individual person has a unique combination of millions of genetic variants that influence virtually all biological processes throughout life, including cancer evolution. In this study, we have investigated the impact of germline variants – genetic defects one is born with – on gene expression and protein abundance in tumors across cancer types.
MedicalResearch.com: Would you describe the technique of precision peptidomics?
Response: We have leveraged a cohort of 1,064 patients with multiple cancer types to explore the impact of germline variations on cancer-relevant genes through multiple-omics layers: from DNA to RNA, protein abundance and post-translational modifications. To assess the effects of coding variants and their association with cognate proteins, we used precision peptidomics, which is the quantification of peptides carrying genetic variants from individual patients. Through this approach, we mapped 337,469 protein coding germline variants onto patient peptides, revealing their potential impact on protein modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases.
Dr. Ådén[/caption]
Ulrika Ådén PhD
Professor of Neonatology
Department of Women's and
Children's Health Karolinska
MedicalResearch.com: What is the background for this study?
Response: Children born preterm are at higher risk of cognitive impairment during childhood and later in life. However, an important unresolved question is whether these impairments primarily reflect genetic susceptibility or are driven by the biological consequences of being born too early. Cognitive development is known to have a strong heritable component (~70 %), and previous studies have attempted to disentangle genetic and environmental contributions, for example through sibling comparison designs. Although informative, such approaches have inherent limitations.
In this study, we aimed to investigate long-term cognitive outcomes across a range of gestational age groups including very preterm, moderately preterm, late preterm, and early term, compared to children born full term. Importantly, we accounted for genetic influences as well as a range of potential confounding factors, including prenatal risks and child-specific factors. This approach provides a more nuanced understanding of the extent to which cognitive outcomes associated with preterm birth reflect biological versus inherited risk.
Dr. Sundar[/caption]
