- Department of Pathology & Immunology (Office)
- Baylor College of Medicine NRI â€“ 1250 Moursund St., Suite 1325.01 Houston, Texas 77030 United States
- Associate Professor
- Baylor College of Medicine
- Houston, TX, US
- Developmental origins of neurological diseases; ataxia; dystonia; tremor; in vivo electrophysiology; deep brain stimulation; genetics
The major goal of my research is to determine the biological bases underlying pediatric neurological diseases. Precise neural circuitry is required for proper brain function. Over the last decade I have shown that circuit organization is a fundamental feature of the mammalian brain and genetic defects that disrupt the formation of organized circuits may cause behavioral deficits observed in human conditions. My current efforts are focused on establishing a wiring diagram for brain circuit map alterations in mouse models of ataxia, dystonia, and tremor.
There has been much progress in identifying genes that are thought to be susceptibility loci in for specific conditions. Despite our rapidly advancing knowledge of the genetic mechanisms underlying these disorders, we do not have a clear picture of what cellular and molecular mechanisms guide neural circuit mis-wiring nor do we appreciate how neural signals are encoded in these defective circuit maps. We see a fundamental problem arising. If we do not understand how brain connectivity is affected, no therapy can be tailored to treat these devastating neurological disorders.
To this end, I am using a combination of mouse molecular genetics, neuroanatomical tract tracing and various developmental biology approaches to investigate the developmental origins of disorders that affect circuit formation. Moreover, we are incorporating into our studies novel in vivo electrophysiology, optogenetics, and deep brain stimulation (DBS) techniques, which will expedite our understanding of how neuronal activity and morphogenetic programs are integrated with gene networks to form functional brain circuits. Using these approaches we have found key circuit pathways that may control brain behavior in multiple disorders and we have uncovered interesting new avenues for restoring motor behavior by modulating brain function.
- Gebre SA, Reeber SL, Sillitoe RV. "Parasagittal compartmentation of cerebellar mossy fibers as revealed by the patterned expression of vesicular glutamate transporters VGLUT1 and VGLUT2.." Brain Struct Funct. 2012 April;217(2):165-80. Pubmed PMID: 21814870
- Reeber SL, Sillitoe RV. "Patterned expression of a cocaine- and amphetamine-regulated transcript peptide reveals complex circuit topography in the rodent cerebellar cortex.." J. Comp. Neurol.. 2011 June 15;519(9):1781-96. Pubmed PMID: 21452228
- Reeber SL, Gebre SA, Sillitoe RV. "Fluorescence mapping of afferent topography in three dimensions.." Brain Struct Funct. 2011 September;216(3):159-69. Pubmed PMID: 21387082
- Strømme P, Dobrenis K, Sillitoe RV, Gulinello M, Ali NF, Davidson C, Micsenyi MC, Stephney G, Ellevog L, Klungland A, Walkley SU. "X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction.." Brain. 2011 November;134:3369-83. Pubmed PMID: 21964919
- Sillitoe RV, Vogel MW, Joyner AL. "Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map.." J. Neurosci.. 2010 July 28;30(30):10015-24. Pubmed PMID: 20668186
- Sillitoe RV, Gopal N, Joyner AL. "Embryonic origins of ZebrinII parasagittal stripes and establishment of topographic Purkinje cell projections.." Neuroscience. 2009 September 1;162(3):574-88. Pubmed PMID: 19150487
- Sillitoe RV, Chung SH, Fritschy JM, Hoy M, Hawkes R. "Golgi cell dendrites are restricted by Purkinje cell stripe boundaries in the adult mouse cerebellar cortex.." J. Neurosci.. 2008 March 12;28(11):2820-6. Pubmed PMID: 18337412
- Esapa CT, Waite A, Locke M, Benson MA, Kraus M, McIlhinney RA, Sillitoe RV, Beesley PW, Blake DJ. "SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA.." Hum. Mol. Genet.. 2007 February 1;16(3):327-42. Pubmed PMID: 17200151
- Marzban H, Sillitoe RV, Hoy M, Chung SH, Rafuse VF, Hawkes R. "Abnormal HNK-1 expression in the cerebellum of an N-CAM null mouse.." J. Neurocytol.. 2004 January;33(1):117-30. Pubmed PMID: 15173636
- Sillitoe RV, Hawkes R. "Whole-mount immunohistochemistry: a high-throughput screen for patterning defects in the mouse cerebellum.." J. Histochem. Cytochem.. 2002 February;50(2):235-44. Pubmed PMID: 11799142