I will be assisting in the behavioral analysis of novel genes that regulates dopamine signaling through the use computer aided visualization and data analysis. With the easy of the model system C. elegans, we can also study how drug treatments act on these novel genes to further dissect their contribution to dopamine action that may yield clues to mammalian brain disorders.
I am a Chemistry major and serve the Blakely lab as a work-study research assistant, supporting a wide variety of laboratory tasks including chemical inventory maintenance, solution preparation and DNA isolation and purification. I provide support for mouse database management and strain genotyping. I work closely with laboratory staff, postdoctoral fellows and students to pursue efforts related to the biochemical properties of neurotransmitter transporters and the genes that encode them.
My research involves understanding the molecular regulation of the serotonin transporter (SERT), which acts to clear serotonin from the synapse after release. Dysregulation of SERT activity has been implicated in a number of neurological disorders including depression and autism spectrum disorder (ASD). Utilizing a gain-of-function SERT coding variant that our lab identified in ASD patients, I am probing for protein-protein interactions that mediate SERT activity.
My project in the Blakely lab utilizes a novel mouse model with a mutation in the dopamine (DA) transporter (DAT) originally identified in two male siblings with attention deficit/hyperactivity disorder (ADHD). This mutation (DAT A559V) results in tonically elevated DA levels in the brain due to DAT-dependent DA leak. Previous work in the lab has demonstrated that animals harboring the mutation have blunted locomotor responses to the psychostimulants amphetamine and methylphenidate, used clinically in the treatment of ADHD, as well as cocaine. Thus far, this work has exclusively focused on male animals because ADHD is four times more prevalent in human males than in females. I will be comparing responses of male and female mice to psychostimulants in an effort to assess possible sex differences and determine whether the clinical gender bias extends to our animal model. The project reflects a growing interest from the NIH in extending funded projects to include the use of female organisms. Our model represents a unique opportunity to model gender bias in psychiatric disease.
I am a Neuroscience Major in the College of the Arts & Sciences. My research involves an investigation of the effects that variants in the human dopamine transporter have on brain signaling cascades. Specifically, I am exploring changes in the DAT Val559 mouse, an ADHD mouse model, in hopes of better understanding the role of dopamine dysfunction in this and related disorders.
Haochen (Emily) Xu
The DAT A559V mouse model is a model of ADHD that was developed in the Blakely lab by knocking-in a mutation (A559V) in the dopamine transporter (DAT) identified in patients with ADHD. Though the mutation fails to impact dopamine (DA) reuptake, it causes DAT to leak intracellular DA into the synapse effectively increasing synaptic DA. My research in the Blakely lab is focused on studying the involvement of the serotonin transporter (SERT) in the loss of locomotor activity in response to cocaine in DAT A559V mice using a combination of genetic and pharmacological approaches. We hope this will provide insight into plasticities that arise from tonically elevated dopamine.