Clarissa Rocca was awarded a Brain Research UK PhD studentship in 2021 to enable her to pursue research into the genetics of cluster headache.
With an undergraduate degree in Biotechnology, and a Master’s in the Genetics of Human Disease, Clarissa worked on the 100,000 Genomes Project at UCL Institute of Neurology before embarking on her PhD. This experience gave her an excellent grounding in the techniques needed to pursue this ambitious and technically challenging PhD, which has advance our knowledge of the genetics underpinning cluster headache.
Clarissa was awarded her PhD in July 2025, and has now secured a prestigious computational postdoctoral position at the National Institutes of Health (NIH), where she will continue her work combining genetics, computation, and neurological disease.
Cluster headache is a rare headache disorder, characterised by recurring bouts of excruciating headaches on one side of the head. It has been described as one of the most painful conditions known to man, with the intensity of the pain often reported to give rise to suicidal thoughts.
It is a condition that impacts very heavily on the lives of patients. The all-consuming pain and unpredictability of attacks can make it hard to carry on a normal life. There are a number of different treatments that aim either to stop the pain during an attack or to stop the onset of attacks during a cluster, but there is no cure.
Read more: About cluster headache
The causes of cluster headache are unknown. This severely limits our understanding of the disease and the development of effective treatments. In order to work towards a cure, we first need to understand more about the underlying causes.
People with close relatives with cluster headache have an increased risk of developing it themselves, suggesting an underlying genetic cause. During her MSc, Clarissa was involved in a study that identified two promising cluster headache genes. For her PhD, Clarissa built on this work – drawing on large national and international genetic databases to understand the roles of these two genes in cluster headache, working out how they cause the symptoms associated with the disorder.
Her PhD focused specifically on genes that control calcium flow in brain cells, particularly CACNA1G, a calcium channel gene. These channels act like small gates, allowing calcium to move into the cells. This process is essential for normal brain signalling, and when it goes wrong, it can trigger disease.
Clarissa studied families with cluster headache and discovered new genetic variants in the CACNA1G gene. In the laboratory, she tested these variants by introducing them into cells and recording how the calcium channels worked. These experiments showed that the variants reduce the normal activity of the channel – a “loss of function” – which helps explain how they could contribute to cluster headache. This is the first strong evidence that CACNA1G is involved in cluster headache. It also highlights calcium channels as a critical pathway in the disease and offers a potential new target for diagnosis and treatment in the future.
While working on CACNA1G, Clarissa also wanted to test whether another type of genetic change - called short tandem repeats (STRs) - might be linked to cluster headache. STRs are stretches of DNA where a sequence of letters is repeated many times. When they become too long, they can disrupt genes and cause disease. To do this, Clarissa generated data on repeats across many neurological genes. Although she did not find STRs directly linked to cluster headache, the analysis showed the value of looking at repeat expansions in unexplained neurological cases.
Cluster headache is a complex and debilitating condition causing excruciating pain. It has a terrible impact on the lives of those affected and the lack of effective treatments limits what can be done to help patients.
Clarissa’s PhD delivered two key insights: that calcium channel dysfunction in CACNA1G is linked to cluster headache, and that STR screening can uncover important genetic causes of neurological disease, even if these are not directly tied to cluster headache.
Together, these findings provide new understanding of cluster headache and point to better ways of diagnosing and eventually treating this debilitating condition.
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