Ataxia is caused by cerebellar dysfunction, which leads to imbalance, loss of hand dexterity, slurred speech, and vision problems. There are multiple causes of cerebellar ataxia, including genetics, immunological disturbances, and nutritional deficiencies. We are interested in the genetic and immunological causes of cerebellar ataxia. We study preclinical models and ataxia patients with an overarching aim to understand the disease mechanism. In addition, we actively participate in the natural history and clinical trials of spinocerebellar ataxias (SCAs) in collaboration with other ataxia centers across the world. Collectively, we hope to discover new therapies for ataxia.
Tremor is the most common form of abnormal movement. People with tremor suffer from discoordination of the hands, head, and voice. Tremor can impair one’s ability to perform daily activities, such as writing, drawing, drinking, and eating. In addition, tremor can cause embarrassment. Essential tremor and Parkinson’s disease are the two most common tremor disorders and it is estimated that millions of Americans are suffering from these disorders. In our lab, we study the pathology of essential tremor and Parkinson’s disease, focusing on the cerebellum and related brain regions. We further establish preclinical models with these pathological alterations to investigate how the morphological changes in the cerebellum can lead to disturbed cerebellar physiology and tremor. By understanding the disease mechanisms and physiology, we will be able to rationally design and test medications that can dampen the tremor.
Post-mortem Human Pathology
Kuo lab studies the structural changes of the cerebellum in ataxia and tremor. Individuals with various causes of ataxia and tremor donate their brains to Columbia University after they pass away, therefore allowing us to further investigate the cause of disease. We perform quantitative pathological analyses of these brains, in collaboration with Drs. Phyllis Faust and Elan Louis, to reveal the origin of where ataxia and tremor come from and to develop therapies targeting these structural changes.
Kuo lab also specializes in preclinical modeling to understand the brain pathology in ataxia and tremor. We use mouse models to simulate the structural changes identified in the brains of patients with ataxia and tremor to test the causal relationship, as well as study the physiological and behavioral changes in these preclinical models. Using optogenetic tools and physiological methods, such as single unit in vivo recording and calcium imaging, we seek to comprehensively understand brain circuitry alterations underlying ataxia and tremor.
Kuo lab has expertise in translational research, which aims to develop tools that can enhance clinical trials and accelerate therapy development for ataxia and tremor. In collaboration with Dr. Ming-Kai Pan, we have developed cerebellar electroencephalogram (cerebellar EEG) technology to interrogate cerebellar physiology in real-time, which can be a novel tool to further probe into the physiology of ataxia and tremor.