Acute Myeloid Leukaemia (AML) results from the accumulation of malignant myeloid blasts in the bone marrow (BM) due to abnormal proliferation and differentiation of haematopoietic progenitor cells. Although current therapies induce high rates of remission there is still an unmet need for new therapeutic strategies as the majority of patients with AML tend to relapse. There is emerging evidence of a crucial role of adhesive interactions between AML leukemic stem cells and the BM normal cells during AML development and resistance to drug treatment.
The objective of this CRUK-funded project led by Dr Yolanda Calle-Patino is to develop a new cell culture method to identify drug combinations that target AML cells and the supportive BM normal cells that could overcome cell adhesion-mediated drug resistance to two drugs commonly used against AML, cytarabine and daunorubicin, and be progressed as new and more effective therapies against AML. Thus this research is of significance to both drug discovery and basic research studies to identify signalling pathways that regulate AML biology. Dr Yolanda Calle-Patino leads her team at Roehampton with Dr Yoana Arroyo (post-doctoral research fellow) and Mariacristina Ciccioli (research student), and collaborates with Professors Lucy Di Sylvio and Eric So of King’s College London, as well as Drs Laurent Lacroix and Volker Behrends (HSRC).
Diabetes is one of the most well-known and rapidly expanding chronic metabolic conditions, affecting more than 3.5 million people in the UK today. The present project led by Dr Astrid Hauge-Evans is focussed on the regulation of insulin production from the beta cell within the pancreatic islet, since beta cell dysfunction is one of the main underlying causes of the disease.
The islets are small, spherical organs scattered throughout the pancreas and this research project investigates how different cell types within these structures communicate with each other and modulate the functional capacity of the islets both with regard to hormone release and beta cell survival. Defining the mechanisms and consequences of intra-islet cell-cell communication is important for identifying novel therapeutic targets for Type 2 diabetes and for designing effective graft material for transplantation therapy of Type 1 diabetes. The research is led by Dr Astrid Hauge-Evans with her team of postdoctoral fellows, Dr Erin Damsteegt and Dr Zoheb Hassan, in collaboration with Professor Peter Jones, Diabetes Research Group, King’s College London.
Multiple Sclerosis (MS) is a devastating autoimmune disease that targets components of the brain and spinal cord. In this condition, the body’s immune system attacks the central nervous system due to a miscommunication between cells. Although no single cause of this disease has been established, there is research evidence that a good supply of vitamin D from sunlight or diet can lower the risk of developing MS. Vitamin D, well-known for its role in bone protection, also exerts complex effects on the immune and nervous systems. Dr Robert Busch leads a project on how vitamin D protects against MS, funded by the MS Society (http://www.mssociety.org.uk) and the MS International Federation (http://www.msif.org/). Dr Busch and his PhD student Nakul Shah are examining how vitamin D influences the production and fate of tissue antigens that have been implicated in genetic risk of MS. They are collaborating with their co-investigator, Professor Jolanta Opacka-Juffry (Health Sciences Research Centre at Roehampton) and Dr Camilla Blain, a consultant neurologist at St George’s Hospital, London who specialises in MS, as well as with researchers at the Cambridge Centre for Proteomics.
More information about Dr Busch’s research is at: /staff/Robert-Busch/
Novel psychoactive substances (NPS), formerly known as 'Legal highs' are increasingly prevalent in Europe and elsewhere although their pharmacological characteristics are largely unknown. NPS with stimulant properties have addictive potential which their users might not realise. Stimulants act at the dopamine transporter (DAT) and subsequently increase dopamine concentrations in the brain, including its reward and addiction pathways.
In the present programme of research led by Professor Jolanta Opacka-Juffry, we use both neurobiological and molecular modelling methods to characterise the stimulant properties of NPS. The molecular modelling studies conducted by Dr Michelle Sahai, an expert in computational biomedicine at Roehampton, reveal the molecular details and patterns of NPS binding with brain targets such as DAT. They also demonstrate the benefits of combining computational methods of biophysics with experimental neurobiological procedures to determine structural and functional properties of NPS at the dopamine transporter as the main molecular target of drugs of addiction. This research is of relevance to the society: NPS users, addiction support and health services as well as policy makers.
The present research is taking place in collaboration with Dr Michelle Sahai (HSRC) and Professor Colin Davidson of the University of Central Lancashire as well as the Blenheim Charity, London www.blenheimcdp.org.uk.
In the last two decades, there has been an increase in Coeliac Disease (CD), a life-long intolerance to gluten proteins present in most cereals, across Europe, the United States and developing countries. Recently, a new and innovative gluten detoxification method has been developed. This technology induces structural modifications of gluten without compromising the nutritional and technological properties necessary to process flour into bread, pasta and other baked goods. The gluten is still present in the modified bread but it becomes unrecognizable by antibodies. As such the modified bread is referred to as “Gluten Friendly” and not “Gluten-free”.
Dr Adele Costabile leads this project at Roehampton, working with her research’s team, Dr Triana Bergillos Meca and Mr Isidro Gonzalez, to investigate the effects of the Gluten Friendly bread on coeliac disease patients. The study will assess the effects on the intestinal permeability, inflammation, immunity and microbiota composition. Furthermore, High-Performance Computing techniques are used to better understand how the 3-dimensional structures of the gluten proteins at the molecular level affect their functional characteristics. So far the in vitro results are encouraging and this project could have a high impact on society through decreasing the incidence of coeliac disease. This project is funded by the University of Foggia, Italy.