Halima Moncrieffe – Single Protein Regulation of Multiple JIA Genes

Halima Moncrieffe – Single Protein Regulation of Multiple JIA Genes

From a young age, Halima Moncrieffe recognized the pain caused by autoimmune conditions. A close friend spent every birthday for fifteen years in hospital suffering from the debilitating effects of Lupus. These experiences at an impressionable age impacted Dr. Moncrieffe deeply. They contributed to her desire right the wrongs caused by autoimmune conditions. She wanted to try and unravel how our life-saving immune system, critical in protecting us from disease and infection, could itself be the cause of such physical destruction. This set her on a determined path to put herself in a position to start answering this key question.

A Quick Study

Halima Moncrieffe was awarded her PhD in immunology from Imperial College London, a significant step towards reaching her goals. She built on this groundwork, becoming an expert in her field of Juvenile Idiopathic Arthritis (JIA) at University College London Institute of Child Health allied with Great Ormond Street Children’s Hospital.

As a young researcher, she quickly built an international reputation that led to her being the only two-time winner of the Pediatric Rheumatology European Society Young Investigator award.  Currently, Dr. Moncrieffe is an assistant professor at the Cincinnati Children’s Hospital Medical Center, where she continues to strive for answers relating to potential causes of, and therefore potential treatment targets for JIA.

Life Changing Experience

Although she has a PhD not clinical training, she sought out the opportunity to be a clinical observer of patients with JIA. Through this, she learned a great deal more than what was available in textbooks. She saw children in pain, with damaged joints, unable to live to their full potential or even to walk. She saw siblings and parents exhausted with caring for their sick loved one and witnessed a double hip replacement in a teenager. Again, she was compelled to ask, why had their immune system – normally so well-calibrated to protect these children – caused so much suffering?

“These experiences helped me articulate to those who did not have the opportunity to see our patients first-hand, that each precious sample provided by our patients and families is never just an anonymized tube, but is always to be treated with full and grateful respect for each patient’s story and the incredible opportunity that we look for answers in a few tablespoons of blood.”  

The Great Unknown

Despite numerous medical advances, there are a number of diseases for which we still do not understand the cause. Diseases that lack a known cause are termed as idiopathic. Juvenile Idiopathic Arthritis (JIA) is one such disease. Dr. Moncrieffe aims to solve the unknown ‘idiopathic’ cause of JIA, providing new treatment hope for patients and their families. This will be the focus of her research as an ANRF scholar.

JIA is the most common form of arthritis in children and adolescents, with onset occurring before the age of sixteen. JIA can be transient, self-limiting or it can be a chronic condition persisting for the rest of a patient’s life. It affects around 1 in 1000 children in the US, with 1 in 10 000 having a more severe form. Symptoms are initially nonspecific but can include lethargy, reduced physical activity and poor appetite. The first manifestation is often limping and flu like symptoms that persist. The cardinal clinical feature is ongoing swelling of the affected joint(s) commonly the knee, ankle, wrist and small joints of the hands and feet. Diagnosis can be made more difficult as joint pain can be from many other causes. No single test can confirm a diagnosis of JIA, and most physicians use a combination of blood tests, X-rays, and clinical presentation to make an initial diagnosis.

Just Cause

JIA is an extremely complex condition. Dr. Moncrieffe believes that difficulty in understanding the mechanisms behind autoimmune conditions such as JIA is due to disease heterogeneity (different characteristics of the disease) and person-to-person variation in the symptoms and causes. As mentioned above, the exact cause of JIA remains unknown but studies have identified that multiple genes are involved, each making small but significant contributions to the development of the condition.

Dr. Moncrieffe is hoping to identify how variation in genes and the interactions between these genes leads to the unwanted and unnecessary inflammation associated with JIA. She believes that with technological advances we are in a position to start to understand our complex genetic architecture in a way that gives us the capacity to recognize what each cell is doing and how it is affecting the dynamic environment that is our bodies. Multiple layers of data regarding our genetics, epigenetics (external factors that impact how our genes are expressed), bacterial and viral exposure and the wider environment in which we exist can be combined to hopefully provide a holistic view of a condition leading to improved treatment options.

Our genes are initiated and regulated by proteins known as transcription factors. Dr. Moncrieffe has previously identified a transcription factor with a common regulatory target that binds to half of all known JIA genes. If a single protein regulates many JIA genes, there would be a foundation for a new type of treatment to turn off many JIA genes at once.

“New treatments continue to emerge and thankfully joint replacements are few and far between. I am inspired to accelerate the hard-earned progress in the field towards a cure. So many talented and brilliant minds are working hard to find the cure, and we always need more so I mentor students and trainees at all stages and let them know that they could be the one to find a cure and impact millions of lives!”

Not Taking it for Granted

Dr. Moncrieffe feels that the as a recipient of an ANRF grant she will have the opportunity to apply cutting-edge methods to a new area of JIA research. She expects this work to become a foundation for the development of new therapeutics and hopefully eventually a cure. “This grant will help me to develop as an emerging leader in the field of functional genomics of JIA.”

 


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ANRF
Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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