Dr Meha Patel, a Wellcome Trust Clinical PhD Fellow in the Macaulay group at the Earlham Institute, exemplifies the power of collaborative research at the Norwich Research Park.
Primary Sclerosing Cholangitis (PSC) is an extremely rare, life-threatening liver disease. Analysing samples from patients in the early stages of the condition, Dr Patel works across the Earlham Institute, Norfolk and Norwich University Hospital and Quadram Institute to generate brand new insights into how the disease progresses.
However, if you had asked Meha about her career aspirations at school, the answer would have been very different.
Growing up, Meha didn’t know what she wanted to do. The only thing she knew for certain is that she didn’t want to be stuck behind a desk. And it was this certainty that led her to pursue work experience at Addenbrooke’s Hospital.
“I really enjoyed being in the hospital environment – I was fascinated by the variety of roles and diversity of patients that made every day so different.” Meha explains.
This experience sparked an interest that led her to pursuing a career in medicine. Despite initially failing to get into medical school, Meha persisted and secured a place at the University of Birmingham. However, it wasn’t plain sailing from there.
“I started to become disillusioned with medicine – I just couldn’t contextualise what I was learning with what I was seeing on the wards. I failed a module in my third year and that was the wakeup call that I needed.”
Dr Meha Patel, Clinical PhD Fellow
Seeking a new direction, Meha took an extra module in cardiovascular research which opened new doors into evidence-based medicine. She changed her pathway and completed an intercalated biomedical sciences degree in Clinical Science, under the supervision of Professor Mark Webber. This incorporated a seven-month basic science laboratory placement focused on antimicrobial resistance mechanisms.
“Mark’s lab was closely linked with Professor Laura Piddock, who at the time of my intercalation was leading the national Antimicrobial Action campaign. This was also the year that Dame Sally Davies as Chief Medical Officer highlighted the dangers of antimicrobial resistance in her annual report. I could directly see how research can drive changes in clinical practice. After completing my intercalation, I just thought about medicine in a different way, it sparked my love of medicine again and I knew I had to have an element of research in my career,” she adds.
After graduating from the University of Birmingham, Meha’s career pathway took one more turn. Initially pursuing her interests in infectious diseases, she applied for an Academic Foundation Programme in Oxford. A chance clinical rotation in Hepatology inspired a change in direction, shifting her research focus to viral hepatitis B, a disease that impacts the liver.
“Hepatology patients are incredibly diverse and can be quite unwell, with a range of pathologies. I knew that this was the direction for me and I wanted to help people suffering from these diseases,” Meha explains.
After moving to Norwich to start Gastroenterology Specialty training and complete an Academic Clinical Fellowship, Meha successfully obtained a Wellcome PhD Fellowship to study PSC. This was through the Wellcome PhD for Clinicians Programme with UEA and the University of Cambridge.
Characterised by inflammation, fibrosis and narrowing of bile ducts, PSC progressively reduces liver function - with liver transplant currently the only available treatment. There are no known treatments beyond management of symptoms, making research undertaken by scientists like Meha vital for improving patient prospects.
The co-location of Earlham Institute, Quadram Institute, and Norfolk and Norwich University Hospital made this research possible
Initially working at the Quadram Institute with Dr Beraza, it soon became clear that Meha’s PhD required her to be closer to the single-cell platforms at the Earlham Institute. Single-cell analysis has proved critical to advancing understanding of PSC. Meha can look at cells in great detail to understand immune cells that may be relevant to the pathophysiology of PSC at an early disease stage. Additionally, she is able to start understanding how immune cells interact with non-immune cells in disease-affected tissues, potentially providing new targets for therapies.
Thanks to support from the Departments of Gastroenterology including Endoscopy, Department of Radiology at the Norfolk and Norwich University Hospital, and the Norwich Research Park Biorepository, Meha has been able to collect samples from patients who are undergoing tissue sampling from the colon, liver and bile ducts in the very early stages of PSC and other autoimmune liver diseases. Critically, this is the first time liver and bile duct tissue from patients at this disease stage have been studied using single-cell RNA sequencing - previous research focused solely on analysing samples collected during liver transplant.
“It’s been challenging but also absolutely brilliant – this project has helped to streamline the infrastructure for health research between the hospital, Earlham Institute, and other institutes across the park – to really allow this to be a Norwich Research Park-wide project,” she says. “The hospital and research institutes being co-localised provides a fantastic opportunity for health research now and in the future”.
Patient wellbeing is at the heart of this research. Samples are only collected when a patient is already undergoing a procedure and protocols have been optimised to work with tiny tissue samples to avoid additional research-specific procedures. Furthermore, the proximity between the hospital and Earlham Institute’s single-cell laboratories, has allowed Meha to streamline the process - from collecting human tissue samples with clinical teams at the hospital to having a single-cell cDNA sample in the freezer in just seven hours – resulting in high-quality, novel sequencing data.
The importance of this research cannot be underestimated for sufferers of PSC. “It’s a horrendous disease and there are no treatments for it. Patients will experience debilitating fatigue, jaundice, recurrent infections and with disease progression, may eventually require a liver transplant. There is so much we don’t know,” Meha explains.
It’s been challenging but also absolutely brilliant – this project has helped to streamline the infrastructure for health research between the hospital, Earlham Institute, and other institutes across the park – to really allow this to be a Norwich Research Park-wide project.
Reflecting on her career so far, Meha says “There have been setbacks and challenges, and we have had to think about each step carefully. Using failures as an opportunity to learn or try something different has led me where I am today.”
Meha’s tenacity in achieving her goals has enabled her to pioneer new approaches to collaborative research - making the most of the opportunities of working on the Norwich Research Park and undoubtedly benefiting the patients who need it most.
“I have absolutely loved completing my PhD at Earlham Institute; there is a fantastic research culture here and coming in as the first clinical PhD student within the Institute, not only have I been welcomed with open arms, but I have had so much support in trying to overcome logistical, governance and technical challenges for this project. I want to continue post-doctoral basic science clinical research and hope to apply for an Academic Clinical Lecturer position in Norwich in due course," she adds.
The next steps for this project involve using the spatial transcriptomic platforms at Earlham Institute, with new pipelines being established with the NNUH Histopathology Department to facilitate this research.
Single-cell and spatial transcriptomic analysis is becoming increasingly effective in unlocking new understanding of rare diseases such as PSC. At the Earlham Institute, these platforms are also being used to study haematological and neurological diseases.
Image: Liver tissue imaged through the Vizgen MERSCOPE spatial platform
