Dr Karthik Ramasamy and Dr John Jacob are both Oxford clinical researchers that have been awarded a Clinical Academic Research Partnership (CARP) by the MRC. Both have been awarded upwards of £200,000 to fund projects investigating myeloma early detection & brain cancer modelling, respectively. Find out more about the projects being funded with this award below.
Dr Karthik Ramasamy
Earlier diagnosis of the bone marrow cancer myeloma is a high priority for patients since it can both improve survival and allow for better control of symptoms. Every case of myeloma is preceded by a condition called Monoclonal Gammopathy of Undetermined Significance (MGUS) and individuals with MGUS are regularly monitored so that progression to myeloma can be caught early.
While this approach is benefitting some patients, there are two main issues that still need to be overcome to improve earlier myeloma diagnosis:
- MGUS is largely symptomless and often undiagnosed, meaning that 80-90% of myeloma patients are diagnosed without first receiving an MGUS diagnosis that would have prompted monitoring for myeloma.
- Only 1% of patients with MGUS progress to myeloma every year and the risk of progression is not well defined, placing a large resource burden for monitoring on healthcare providers and creating anxiety for patients.
In this MRC CARP award, Dr Karthik Ramasamy will address both of these challenges. Firstly, working with Professor Kassim Javaid, Professor Daniel Prieto-Alhambra, Dr Constantinos Koshiaris and data from primary care health records, Dr Ramasamy will identify specific clinical signs/symptom clusters associated with MGUS to enable a greater proportion of individuals with MGUS to be diagnosed and monitored. Secondly, additionally collaborating with Dr Ross Sadler, Professor Chris Schofield and Professor James McCullagh, Dr Ramasamy will seek to identify routinely recorded clinical characteristics and additional protein biomarkers that improve prediction of progression from MGUS to myeloma in a cohort of patients undergoing monitoring at Oxford University Hospitals NHS Trust. This latter work is bolstered by a recently awarded CRUK Oxford Centre Development Fund award, which will enable the research team additionally to pilot protein glycosylation analysis in blood samples collected as part of a current study investigating serological markers in plasma cell dyscrasias (BLOOM).
Dr Karthik Ramasamy is Lead Clinician for myeloma and other plasma dyscrasias in Thames Valley Strategic Clinical Network and Divisional Lead of Cancer Research across Thames Valley and South Midlands Research Network.
Dr John Jacob
Brain cells that originate in the cerebellum give rise to the most common childhood brain tumour, known as medulloblastoma, which can also affect adults. Although it can be cured, it is often a devastating disease, with common treatment options resulting in an increased risk of adverse side effects such as strokes and seizures.
Like most cancers, the development of new treatment options that improve survival rate and reduce side effects is reliant on researchers establishing models that reflect the human tumours, in order to test the efficacy of new therapeutics before these are tested in patients. Existing models for medulloblastoma have shortcomings making the discovery of new treatment options slow. This is due to:
- Growing medulloblastoma cells outside of a patient is hard, due to the change in environmental factors. Growing cells outside the body usually does not accurately reflect the microenvironment that cells are derived from, and so the cells will behave differently and unlike a real tumour. As a result, only a few cell lines from medulloblastoma patients have been successfully grown ex vivo.
- Models can be costly, and these include mouse-based models, which pose limitations due to the difference in species
- Medullobastoma tumours are genetically different between patients – there is no ‘one size fits all’ model and there is a need to develop more treatment options that target specific genetic subtypes in order to improve survival.
In this CARP award, Dr John Jacob (Nuffield Department of Clinical Neurosciences) aims to investigate a specific genetic subtype of medulloblastoma (known as sonic hedgehog medulloblastoma) – and test if the presence of the tumour microenvironment, which consists of non-cancerous cerebellar tissue, is necessary to better simulate the typical tumour growth conditions.
Working alongside Associate Professor Esther Becker (Nuffield Department of Clinical Neurosciences) and Dr Benjamin Schuster-Boeckler (Big Data Institute & Oxford Ludwig Cancer Institute), the team hope to recreate the in vivo tumour microenvironment more accurately compared to existing models. The Becker group previously established a methodology to grow human cerebellar neurons from human induced pluripotent stem cells (hiPSC). By using hiPSCs to form miniature cerebellar structures, termed cerebellar organoids, the tumour microenvironment can be recreated in a dish.
The team hope to overcome the existing modelling difficulties by growing medulloblastoma cells on these organoids. Dr Jacob, aided by the computational biology expertise of Dr Schuster-Boeckler will then investigate the growth of individual tumour cells, in a more physiological context. The resulting outcomes could mean the development of a new model to test patient-specific therapies on, in order to assess their toxicities and efficacy more accurately.
Dr John Jacob is a consultant neurologist who is interested in better understanding the genetic complexity of cancer and what it means for personalised treatment. Through this award and collaboration, Dr Jacob hopes to improve the success of therapy development and ultimately improve the repertoire of therapies of this cancer.
The Medical Research Council Clinical Academic Research Partnership scheme allows NHS consultants with a PhD or MD to participate in collaborative high-quality research partnerships with established leading biomedical researchers.