Duncan NRI Vishnu Cuddapah, MD, PhD

Our group seeks to understand interactions between neurodevelopmental disorders, sleep, and circadian rhythms. We are particularly interested in learning how epilepsy – one of the most common neurodevelopmental disorders – is regulated by sleep and circadian rhythms. To do this, we leverage the tractability of fruit flies. By uncovering underlying mechanisms, we hope to identify new therapeutic targets to improve seizure control and gain insight into the biology of sleep. 

In parallel, we are trying to understand what causes sleep dysfunction in people. We are involved in efforts to perform genetic sequencing of people with severe sleep or circadian symptoms. Our hope is to translate an understanding of underlying genetic etiologies into novel therapies that improve sleep quality.

We are primarily focused on four research questions:

• How does poor sleep lead to increased seizure risk in people with epilepsy? 
  When people with epilepsy do not sleep well, seizure risk increases. We found, using unbiased approaches in flies, that increased activity of sleep-promoting circuits increases seizure risk. Current projects are focused on understanding how sleep-promoting neurons can control brain-wide excitability. We also seek to gain insight into why seizures in sleep can be lethal.
   
• How do circadian circuits regulate the timing of seizures?
  Seizure occurrence is not random. Instead, seizures tend to cluster at particular times of the day in people with epilepsy. Using chronic video tracking in flies, we seek to understand if brain clock neurons time neurological symptoms including seizures.
   
• Do variants in circadian clock genes have neurodevelopmental consequences?
  Children with neurodevelopmental disorders very commonly experience sleep/circadian disturbances. Our team is interested in understanding if pathogenic variants in molecular clock genes have neurodevelopmental effects.
   
• How does genetic variation contribute to sleep/circadian disorders in people?
  Little is known about the underlying causes of severe sleep and circadian disease. We seek to identify novel monogenic etiologies for sleep and circadian disorders in people.