Professor, Department of Pathology & Immunology, and Department of Neuroscience, Baylor College of Medicine
Director, Neuropathology Core, Jan and Dan Duncan Neurological Research Institute
Principal Investigator, the Jan and Dan Duncan Neurological Research Institute
Chao Family Endowed Chair
Research Focus: Genetic, cellular and circuit mechanisms of neurodegeneration
The primary interest of the Sillitoe Lab is to determine the mechanisms that lead to neurodegeneration. From a global health perspective, neurodegeneration has a major impact on society because it contributes to a growing list of devastating neurological and neuropsychiatric conditions, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and autism spectrum disorders. Dr. Sillitoe studies a region of the brain called the cerebellum to investigate how neurodegeneration influences neuronal health, circuit wiring, and daily behaviors. In this regard, the cerebellum is an ideal system to study since it controls motor functions such as limb coordination and balance, as well as non-motor functions including cognition and emotion.
The Sillitoe Lab uses an interdisciplinary experimental approach that combines sophisticated mouse molecular genetics with high-resolution neuroanatomy, behavioral paradigms, and in vivo electrophysiology to measure the impact of neurodegeneration on circuit function and animal behavior.
There are three main research streams in the lab. In the first, Dr. Sillitoe’s team is identifying how mutations in different genes alter the development and maturation of circuits and how insults that target the developing brain eventually lead to neurodegeneration. In the second stream, the Sillitoe group has devised methods to “record” brain signals in actively behaving mice. These techniques provide the lab with key opportunities to identify how degenerating neurons signal one another. These data are directly relevant to the third stream of work. By understanding the abnormal signaling properties of degenerating neurons, Dr. Sillitoe and his research team have been able to develop therapeutic approaches that correct the erroneous brain activity. The ultimate goal of his lab is to uncover novel biological brain markers that could inspire early intervention in neurodegenerative conditions, with the goal of improving the quality of life in affected individuals.
In addition to the widely applicable mechanisms of neurodegeneration, the Sillitoe Lab also studies cerebellar-associated diseases, including ataxia, dystonia, and tremor. Recent work has also focused on cerebellar dysfunction in severe epilepsy. Thus, the Sillitoe lab studies how the brain forms, how it fails, and how to repair it.
White JJ, Arancillo M, King A, Lin T, Miterko LN, Gebre SA, Sillitoe RV. Pathogenesis of severe ataxia and tremor without the typical signs of neurodegeneration. Neurobiol Dis. 86:86-98 (2016). PMCID: PMC4778569
White JJ and Sillitoe RV. Genetic silencing of olivocerebellar synapses causes dystonia-like behaviour in mice. Nat Commun 8:14912 (2017). PMID 28374839