Sanaria Fathulla (SF): Can you briefly talk about your academic background and how you became interested in researching vascular calcification?

Samantha Borland (SB): I completed my undergraduate degree at the University of Manchester. Initially, I was a bit undecided about my specific field of interest, so I started with Biomedical Sciences in my first year. One of the great things about Manchester was the flexibility to switch degrees, and as I became more interested in Pharmacology and Physiology, I transitioned into that field in my second year.

During my studies, I saw many of my friends pursuing placement years, which seemed like a valuable opportunity to gain experience and enhance my CV. I decided to follow suit and spent a year at AstraZeneca, working in the safety pharmacology department. My role involved developing a guinea pig model to test the effects of drugs on heart rate, cardiac contraction, and blood pressure, and this led my first publication (Marks et al., 2012). This experience was incredibly engaging, and it made me realise how much I enjoyed lab work and research.

Before that, I had never really considered a lab-based career. Like many students, I had chosen science because it was my strongest subject, but I wasn't sure what I wanted to do with it. However, my placement year was a turning point. It was during that time that I became particularly interested in cardiovascular research. When I returned for my final year, I worked on a sheep model of heart failure, which further reinforced my interest in the field.

Wanting to continue in cardiovascular research, I applied for PhD programs. I was fortunate to secure a place in a four-year British Heart Foundation-funded program at the University of Manchester. The program involved rotating through three different labs in the first year before selecting a final research focus. Initially, I thought I would continue working with animal models, but one of my rotations was in vascular calcification—something I had never encountered before. I found the topic fascinating, and my supervisor had an interesting PhD project in mind for me, so I decided to pursue it.

Ultimately, my PhD marked a shift in my research focus—from animal models to cell culture studies. At the end of my PhD, I wasn’t entirely sure what to do next, but I had an idea for a research project, and with the support of my supervisor, we secured funding. That project launched my postdoctoral career at Manchester before I eventually moved here to Salford.

Aliya Sajid (AS): Can you give us an overview of your current research focus?

SB: My current research still revolves around vascular calcification, with a specific focus on a protein called PKCα. I actually started investigating this protein during my PhD. My findings showed that inhibiting or knocking down PKCα using small interfering RNA led to increased calcification in cell culture models. However, cell culture has its limitations, so my postdoctoral research focused on exploring PKCα in animal models.

Using a mouse model of chronic kidney disease, I showed knocking down PKCα resulted in increased calcification, which matched my cell culture findings. This was an important step in understanding the protein’s role in the disease process. However, since knocking it down led to more calcification, that wouldn't be a viable treatment approach for patients. My recent research has focused on whether activating PKCα could inhibit calcification

So far, my results are promising—activating PKCα appears to reduce calcification. The challenge, however, is that PKCα has numerous functions throughout the body. Since it’s expressed in various tissues, we have to consider potential side effects of targeting it therapeutically. That’s why I’ve recently become more interested in investigating the downstream signalling pathways which are regulated by PKCα. If we can identify specific pathways responsible for its calcification-related effects, we might be able to target them instead, reducing the risk of off-target effects elsewhere in the body.

Clinically, vascular calcification is a major concern, particularly for patients with chronic kidney disease, as it significantly increases their risk of mortality. Currently, there are no approved treatments to prevent or reverse calcification, making this research particularly relevant. Given the high prevalence of chronic kidney disease in the Manchester area, I hope that by understanding these mechanisms better, we can develop effective therapeutic strategies in the future.

SF: Since there are no approved treatments for vascular calcification, what therapies—whether drug repurposing or novel interventions—show the most potential for clinical application?

SB: Right now, one of the most promising treatments in clinical trials is a drug called SNF472. It has shown potential in preclinical studies and early-phase clinical trials, but the latest Phase 3 clinical trial did not meet either of its primary efficacy outcomes.

Another emerging area of interest is the use of natural compounds derived from plants. Since moving to Salford, I’ve become more involved in this line of research. One plant-derived compound asiaticoside has shown some promise in reducing calcification. However, this is still in the early stages, and not many researchers are currently exploring this route. Overall, drug repurposing is a strategy that has proven highly effective in other fields, such as atherosclerosis, but hasn’t been widely applied to vascular calcification yet. There is significant potential in identifying existing drugs that could be repurposed for this condition, particularly as their safety profiles are already well established. Hopefully, future research will explore these possibilities further.

AS: You utilise various experimental techniques like X-ray micro-computed tomography and immunohistochemistry to study vascular calcification. How have these methods helped uncover new insights into this pathology?

SB: X-ray micro-computed tomography (MicroCT) has been a game-changer, especially for my work with animal models. Traditionally, researchers would assess calcification by removing the aorta from a mouse model and measuring calcium content using biochemical assays. The downside to this approach is that it destroys the tissue, preventing any further analysis. To obtain additional data, researchers would need to use multiple mice, which is not ideal from a 3R’s standpoint (replacement, reduction, refinement).

MicroCT allows us to scan the entire aorta while preserving the tissue, enabling us to quantify calcification and then use the same sample for further analysis, such as immunohistochemistry. This significantly reduces the number of animals required and provides a more comprehensive understanding of the extent and distribution of calcification. Immunohistochemistry, on the other hand, helps us investigate the signalling pathways involved in calcification by identifying which proteins are upregulated or downregulated in diseased tissues. Together, these techniques offer a more detailed and ethical approach to studying vascular calcification.

SF: Since vascular calcification is often considered an irreversible process, should future treatments focus more on prevention, or is there potential for reversing existing calcification?

SB: As far as I know, there are currently no treatments capable of reversing vascular calcification once it has formed. The best approach appears to be prevention—stopping calcification from progressing in high-risk patients. One major challenge is early detection. Identifying calcification in patients requires imaging techniques like CT or MRI, which are not routinely used in screenings.

For high-risk patients, particularly those with chronic kidney disease, early implementation of preventative strategies—whether through medication, dietary modifications, or other interventions—could prove beneficial. But at the moment, we lack effective interventions, so further research is needed to fill this gap.

AS: What advice would you give to early-career researchers interested in vascular calcification?

SB: My main advice is to gain as much experience as possible. Many undergraduates don’t consider research as a career path simply because they haven’t been exposed to it early on. If you’re interested, attend research talks, seek out summer internships, and ask lecturers or researchers if you can gain experience in their labs.

Research is a competitive field, and having hands-on experience will help you stand out. Even if you are unsure about pursuing a PhD, getting involved in research during your degree can open up a wide range of career opportunities. Take advantage of every opportunity available, and most importantly, find an area of research that excites you!

References

Marks, L., Borland, S., Philp, K., Ewart, L., Lainée, P., Skinner, M., Kirk, S., & Valentin, J. P. (2012). The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds. Toxicology and Applied Pharmacology , 263 (2), 171-183. https://doi.org/10.1016/j.taap.2012.06.007