Associate Professor, Baylor College of Medicine
Co-Director, Program in Developmental Biology
Ph.D., The University of Calgary, Canada, 2003
Developmental origins of complex neurological conditions
The major goal of my research is to determine the biological bases underlying complex 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 Autism Spectrum Disorder, Obsessive-Compulsive Disorder, hereditary ataxia, and dystonia.
There has been much progress in identifying genes that are thought to be susceptibility loci in all four 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 molecular genetics, neuroanatomical tract tracing, biochemistry, and imaging to investigate the developmental origins of disorders that affect circuit formation. Moreover, we are incorporating into our studies novel in vivo electrophysiological approaches, which will expedite our understanding of how complex embryonic 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. Strikingly, our preliminary data demonstrates that pharmacologic drugs and maternal-neonatal social interactions provide strong therapeutic value by repairing these circuits when they are damaged by genetic insults in utero.
Sillitoe RV, Hawkes R (2002) Whole-mount immunohistochemistry: a high-throughput screen for patterning defects in the mouse cerebellum. Journal of Histochemistry and Cytochemistry 50:235-244.
Sillitoe RV, Benson MA, Blake DJ, Hawkes R (2003) Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy. Journal of Neuroscience 23:6576-6585.
Esapa CT, Waite A, Locke M, Benson MA, Kraus M, McIlhinney RA, Sillitoe RV, Beesley PW, Blake DJ (2007) SGCE missense mutations that cause myoclonus-dystonia syndrome impair ε-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA. Human Molecular Genetics 16:327-342.
Sillitoe RV, Chung SH, Fritschy JM, Hoy M, Hawkes R (2008) Golgi cell dendrites are restricted by Purkinje cell stripe boundaries in the adult mouse cerebellar cortex. Journal of Neuroscience 28:2820-2826.
Sillitoe RV, Stephen D, Lao Z, Joyner AL (2008) Engrailed homeobox genes determine the organization of Purkinje cell sagittal stripe gene expression in the adult cerebellum. Journal of Neuroscience 28:12150-12162.
Sillitoe RV, Gopal N, Joyner AL (2009) Embryonic origins of ZebrinII parasagittal stripes and establishment of topographic Purkinje cell projections. Neuroscience 162:574-588.
Sillitoe RV, Vogel MW, Joyner AL (2010) Engrailed homeobox genes regulate establishment of the cerebellar afferent circuit map. Journal of Neuroscience 30:10015-10024.
Strømme P, Dobrenis K, Sillitoe RV, Gulinello M, Ali NF, Davidson C, Micsenyi MC, Stephney G, Ellevog L, Klungland A, Walkley SU (2011) X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction. Brain 134:3369-3383.
Reeber SL, Gebre SA, Sillitoe RV (2011) Fluorescence mapping of afferent topography in three dimensions. Brain Structure and Function 216:159-169.
Reeber SL, Sillitoe RV (2011) Patterned expression of a cocaine- and amphetamine-regulated transcript peptide reveals complex circuit topography in the rodent cerebellar cortex. Journal of Comparative Neurology 519:1781-1796.
Gebre SA, Reeber SL, Sillitoe RV (2012) Parasagittal compartmentation of cerebellar mossy fibers as revealed by the patterned expression of vesicular glutamate transporters VGLUT1 and VGLUT2. Brain Structure and Function 217:165-180.
Roy V. Sillitoe, Ph.D.
Department of Pathology & Immunology
Baylor College of Medicine
NRI – 1250 Moursund St., Suite 1325.01
Houston, Texas 77030, U.S.A.
Tel: (832) 824-8913
Fax: (832) 825-1251