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Research project on modulating the inflammatory re sponse in Crohn's disease and COVID-19.
YOUR DONATION WILL ENABLE RICHARD & MO TO:
  1. Examine difference in genes and proteins levels specific to epigenetic mechanisms between inflammatory cells from patients and healthy individuals.
  2. Assess the response of inflammatory cells after being treated with GSK- J4.
  3. Assess the toxicity of GSK-J4 on cells.
  4. Build a case for the rational of using GSK-J4 to treat patients with severe Crohn’s disease. 
Research project on a novel epigenetic pro-drug for the early, accurate detection of bowel cancer.

YOUR DONATION WILL ENABLE RICHARD & MO TO:

  1. Characterise the molecular composition of microvesicles in patients suffering from colorectal cancer.
  2. Assess the reliability of finger-prick capillary blood and urine as alternative sampling methods for microvesicles analysis.
  3. Develop and validate a microvesicles purification prototype (microvesicles analyser).
  4. Assess the compliance rate, acceptability and feasibility of a microvesicles test (MVT).

Manufacture of a microvesicles probe.

Design the study to compare and validate the microvesicles probe against the current test.

UCL research project on a novel epigenetic pro-drug for modulating the inflammatory response in Crohn's disease.

Background: Patients suffering from  inflammatory conditions, such as Crohn’s disease are burdened by an imbalanced immune response. This accounts for the body’s immunity harming one’s own cells, akin to a civil war.

Currently, patients living with Crohn’s disease spend their entire life receiving medical care to alleviate their symptoms. Despite the advancement of medical sciences these conditions remain incurable.

The challenge: The potential therapies that currently exist to treat Crohn’s disease aim to regulate the immune response. However, the benefits are limited to approximately half of the patients with severe Crohn’s disease, while the patients who resist current treatment modality end up with very limited therapeutic options. For example, infliximab, an expensive immune-suppressive treatment often used to treat Crohn’s disease patients is effective in 35% of the patients at most.

The need for new ways to modulate the immune response in these patients is urgent.

Hypothesis: Our approach to modulate the inflammation in Crohn’s disease is by modifying the immune cells’ response. Changing the way cells would produce proteins that perpetuate the inflammation in the bowel.

Specifically, we hypothesise that the immune cells in Crohn’s disease patients have an increased level of a cellular enzyme called KDM6B, which subsequently reduces the threshold of an inflammatory response, enabling the production of inflammatory proteins. In a normal response this will trigger mechanisms that allow the body to fight infections or heal wounds by clearing affected or damaged cells. Once damaged cells are removed, feedback mechanisms subside the inflammation to the basal state. When a balanced response is lost gross damage to the bowel occurs.

GSK-J4 is the name of a novel pro-drug with therapeutic potential to treat inflammatory disorders, such as but not limited to Crohn’s disease. GSK-J4 would inhibit KDM6B preventing an exaggerated and perpetuated inflammatory response.

The Research: Our objectives are as follows:

  1. To examine difference in genes and proteins levels specific to epigenetic mechanisms between inflammatory cells from patients and healthy individuals
  2. To assess the response of inflammatory cells after being treated with GSK-J4
  3. To assess the toxicity of GSK-J4 on cells
  4. To build a case for the rational of using GSK-J4 to treat patients with Crohn’s disease

The difference this research will make: Novel immunomodulatory therapy, such as GSK-J4 could have a wide implication on the treatment of patients suffering from a wide variety of systemic inflammatory response and other inflammatory conditions.

This is a new approach that can save lives.

UCL research project on a novel epigenetic pro-drug for the early, accurate detectioof bowel cancer.

Background: Colorectal cancer (CRC) is the second cause of cancer death worldwide and the incidence is rising among younger people. Early detection before symptoms occur is the key to improving survival and quality of life.

The stool-sampling test adopted by the bowel cancer screening programme for early detection has poor predictive value and compliance rate, with many people finding the sampling method challenging.

The challenge: To develop a test that is likely to go far beyond the current state-of-the-art, promising significantly better predictive value and acceptability among populations of different demographics and cultural backgrounds.

The science behind the project: Microvesicles are miniscule (submicron) particles that shed from cells when they become activated. When they enter the circulation, they exemplify molecular biopsies from the cell of origin. They can be isolated from blood and urine and employed as biomarkers for early detection of colorectal cancer. This approach is plausible, novel and offers a favourable solution in the management of colorectal cancer.

Hypothesis: That microvesicles as biomarkers provide a superior predictive value for precancerous and cancerous colorectal tumours and a sampling method that is more acceptable and would improve the compliance rate for bowel cancer screening when compared against the current Faecal Immunochemical Test (qFIT).

The Research: Will quantitatively and qualitatively validate the potential role of microvesicles as biomarkers for colorectal neoplasia, with four objectives in mind:

  1. To characterise the molecular composition (cargo) of microvesicles in patients suffering from colorectal cancer.
  2. To assess the reliability of finger-prick capillary blood and urine as alternative sampling methods for microvesicles analysis.
  3. To develop and validate a microvesicles purification prototype (microvesicles analyser).
  4. To assess the compliance rate, acceptability and feasibility of a microvesicles test (MVT).

The difference this research will make:The Microvesicles Test would enable the early identification of CRC, allowing effective treatment and cure.

Bowel cancer is treatable and curable especially if diagnosed early and nearly everyone survives bowel cancer if diagnosed at the earliest stage, why the need for early detection of cases is dire, not only to prolong life span, but to offer better quality of life.

The burden of untreatable, late diagnosed cancer is immense, not only on individual patients and their families, but also on the society as a whole.

This research proposal is designed to push the boundaries of frontiers of science in pursuit of identifying colorectal cancer cases early, in the golden time-window when chances of cure are very high.

Ultimately, this will improve patient outcomes and save costs by cutting the chain of unnecessary invasive investigations.

UCL, together with the inventors, currently own UK & international patents on the microvesicles as biomarkers for bowel cancer.  

Having always wanted to become a doctor, so that I can alleviate the suffering of patients,
I realised early in my medical career that one of the best ways to achieving a high impact on patient’s care is to arm myself with advanced research skills.

Shortly after my medical school and completion of the first year as a doctor, I went on to study a master’s degree in transfusion and transplantation sciences at the University of Bristol. Not only did I improve my skills in the field of biomedical sciences, but also medical research.

My next goal was to complete a PhD alongside my surgical training. In 2017, I defended my theses at UCL on studying Crohn’s disease. My work at UCL with Professor Richard Cohen sharpened my research skills and opened the horizon for medical invention.

In 2021, I became the first inventor on a biomarker that would potentially identify patients with severe disease early before symptoms occur. I was also fortunate to be trusted by the Oxford Structural Genomics Consortium to investigate one of their epigenetic therapies which could, potentially, improve the lives of patients suffering from formidable inflammatory conditions, such as Crohn’s disease. We have now drafted our second manuscript in the field.

I am now looking to progress these fields, using my clinician scientist skills to enable the translation of laboratory scientific advancements into patients benefit.

Richard Cohen trained at the Cambridge University School of Clinical Medicine where he qualified with a distinction in surgery. He then became a surgery registrar in the north west of England and a senior registrar on the Guy’s and St Thomas’ surgical training program. Alongside his clinical training he carried out research at Yale University and defended his MD thesis at Cambridge University.
A clinical interest in specialist colorectal surgery led to a post as a Resident Surgical Officer at St Mark’s Hospital for a year shortly before being appointed as a consultant surgeon at St Mark’s Hospital and Central Middlesex Hospital.

He then moved to UCLH in 2005 where he helped to develop the colorectal service and became involved in leadership holding Divisional Clinical Director positions in Theatres and GI Services  and then Trust Clinical Director of Patient Flow.

He maintains a clinical practice in open and minimally invasive colorectal surgery focusing on proctology, colorectal cancer and benign colorectal disease including the management of ulcerative colitis, Crohn’s disease and inflammatory bowel disease.

 He has always run research projects since his appointment as a consultant in 1999 and  has shown a keen interest in academic research in the areas of Crohn’s disease and bowel cancer. He  has supervised several  theses at Imperial and then UCL. 

He is currently Professor of Surgery at UCL.