1) Cerebellar Ataxia

The hereditary, or familial, cerebellar ataxias are a collection of rare genetic disorders that cause progressive destruction of the cerebellum and subsequent impairment of balance and coordination. Ultimately, this can render patients unable to walk and care for themselves. Although more than 100+ genes have already been identified which can cause cerebellar ataxia, the etiologies behind up to 50% of affected families still remain unknown. We are studying undiagnosed families and individuals using genome-wide techniques, including next-generation exome sequencing, to identify novel and rare causes of genetic ataxia, including new disease genes. We are also examining the specific molecular effects of mutations in various ataxia genes to determine what causes the severe neurodegeneration seen in this insidiously progressive disorder. 

2) Ataxia with Oculomotor Apraxia (AOA2)

Our laboratory studies Ataxia with Oculomotor Apraxia Type 2 (AOA2), a genetic form of cerebellar ataxia caused by mutation of the senataxin gene (SETX), which is involved in regulating gene expression and the stability of the genome. AOA2 typically begins in adolescence and is one of the most common recessive ataxias worldwide. Many different AOA2 mutations have been reported that appear to impair senataxin function. We have recently shown that by studying the expression of all human genes within multiple AOA2 families, a conserved disease-specific molecular signature can be observed that specifically identifies AOA2 patients and likely reflects the disruption of specific cellular pathways important in cerebellar function. At present, there is no cure and no disease-specific treatment available and our laboratory is interested in developing a better understanding of the normal function of senataxin and the effects of its mutations to aid development of such treatments in the future.

3) Autism Spectrum Disorder

Autism spectrum disorder is a neurodevelopmental condition defined by variable degrees of impairment in socialization, language, and behavior which affects one out of every 68 children and can lead to lifelong disability. We are examining specific genes associated with rare forms of ASD to identify the critical molecular pathways and genetic programs in neurodevelopment that are affected. These discoveries may help to better understand other causes of ASD, provide new means of diagnosis, and aid development of new therapies.