I have always been fascinated by neuroscience and brain development. Research advances over the past decade have uncovered important aspects of brain function as well as the specific neural circuits that control them. However, we’re still investigating how these circuits, especially those related to neuropsychiatric disease, are established and refined.
Since joining Cincinnati Children’s in 2001, I’ve studied the development of neural circuits in the mammalian forebrain, particularly those that comprise the basal ganglia. Degeneration of these brain circuits, which control voluntary movements, leads to most of the behavioral changes observed in Parkinson's disease and Huntington's disease. Interestingly, because these neural circuits are responsible for appropriate behavior, they are implicated in childhood neuropsychiatric disorders, such as attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), Tourette syndrome and autism spectrum disorder (ASD).
My colleagues and I hope to uncover the molecular genetic mechanisms that control the normal formation of basal ganglia circuits. By disrupting or augmenting these circuits' formation, we hope to learn how normal behaviors are altered. This knowledge will help us generate mouse models of certain behaviors that characterize childhood neuropsychiatric disorders, paving the way for the development of improved therapeutics.
Our research group has been instrumental in characterizing the embryonic neural progenitor sources of the different neuronal subtypes that comprise the basal ganglia and broader ventral telencephalic neuronal subtypes. We have also contributed significantly to the current understanding of how these progenitor domains are established in the developing brain.
In 2012, I was named the Robert and Sarah McLaurin Chair in Pediatric Neurosurgery. In this role, I oversee and mentor the basic research activities of faculty in the Division of Pediatric Neurosurgery. I also serve on the editorial boards of two journals, the Development and Developmental Neuroscience.
MS: University of Toronto, Toronto, Canada, 1990.
PhD: Lund University, Lund, Sweden, 1994.
Postdoctoral Fellow: Skirball Institute, NYU Med Center, 1995-97.
Developmental neurobiology; transcriptional control of neural cell subtype specification; neuronal circuit formation
Developmental Biology, Neurosurgery
Formation of the Mouse Internal Capsule and Cerebral Peduncle: A Pioneering Role for Striatonigral Axons as Revealed in Isl1 Conditional Mutants. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022; 42:3344-3364.
Conserved Gsx2/Ind homeodomain monomer versus homodimer DNA binding defines regulatory outcomes in flies and mice. Genes and Development. 2021; 35:157-174.
Physical interactions between Gsx2 and Ascl1 balance progenitor expansion versus neurogenesis in the mouse lateral ganglionic eminence. Development (Cambridge). 2020; 147:dev185348.
Loss of Intercalated Cells (ITCs) in the Mouse Amygdala of Tshz1 Mutants Correlates with Fear, Depression, and Social Interaction Phenotypes. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2018; 38:1160-1177.
The LIM homeobox gene Isl1 is required for the correct development of the striatonigral pathway in the mouse. Proceedings of the National Academy of Sciences of USA. 2013; 110:E4026-E4035.
Conserved and Distinct Functions of the Autism-Related Chromatin Remodeler CHD8 in Embryonic and Adult Forebrain Neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022; 42:8373-8392.
The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2022; 42:1820-1844.
Olig2 defines a subset of neural stem cells that produce specific olfactory bulb interneuron subtypes in the subventricular zone of adult mice. Development (Cambridge). 2022; 149:dev200028.
Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment. Translational Psychiatry. 2022; 12:22.
Temporally Distinct Roles for the Zinc Finger Transcription Factor Sp8 in the Generation and Migration of Dorsal Lateral Ganglionic Eminence (dLGE)-Derived Neuronal Subtypes in the Mouse. Cerebral Cortex. 2021; 31:1744-1762.