The Holder Lab
Dr. Holder is a Primary Investigator, Assistant Professor in the Department of Pediatrics and Developmental Neuroscience, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital.
Research Focus: Neurodevelopmental disorders, Autism, SHANK3 mutations
The SYNGAP1 Foundation's, formerly Bridge the Gap's first research grant was awarded to Dr. Jimmy Holder in September 2019. This research grant will fund a clinical study to find biomarker(s) for this disorder that will be used in conjunction with primary research to develop targeted therapies.
Principal Investigator, Assistant Professor, Baylor College of Medicine, Texas Children's Hospital
Holder Research Lab
Jan and Dan Duncan Neurological Research Institute
The Holder lab investigates neurodevelopmental and neuropsychiatric disorders' genetic and neurobiological basis. There are currently three main projects in the Holder Lab.
First, we use cell-based screens to identify genetic modifiers of two synaptic proteins, SHANK3 and SynGAP. Mutations in the SHANK3 and SYNGAP1 genes cause severe neurodevelopmental disorders associated with intellectual disability, autism, and epilepsy. Both are typically caused by de novo mutations which result in haploinsufficiency. We aim to identify therapeutic entry points for these disorders by identifying genetic modifiers of protein stability. Verifying a physiological role for genes identified through these screens will be performed in patients' animal models and iPSC-derived neurons.
Second, we investigate the neuronal and circuit dysfunction responsible for the phenotypes associated with SHANK3 Duplication Syndrome. We are currently focusing on the role of striatal neurons in behavioral abnormalities of mice modeling this disorder. Our lab uses Cre-LoxP and Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to map the neurons responsible for these behavioral abnormalities.
Third, we are investigating the role of genetic variants on bipolar disorder. We use next-generation sequencing to identify genetic changes predisposing to bipolar disorder in families. We then propose to use animal models of these changes to validate their role in neuropsychiatric disorders.