Neurogenetics & Neurodegenerative Research Groups
The Pulst laboratory has several research groups with the overall goal to understand human neurological diseases by identifying genetic mutations and genetic variations that cause or contribute to disease. These insights are then used to model diseases in cells and animals with the ultimate goal to identify novel treatments for these diseases. Graduate students, medical students, neurology residents and fellows as well as postdoctoral fellows have all participated in various research projects.
Spinocerebellar Ataxias (SCAs)
The ataxia research groups tries to understand the molecular genetic basis of spinocerebellar ataxias (SCAs). We have used genetic linkage analysis and positional cloning to identify SCA genes followed by the generation of in vitro and in vivo models. Currently, we are evaluating the roles of ion channels on cerebellar function and neuronal survival (PI: SM Pulst, DH Scoles).
Mutations in the Ataxin-2 cause SCA2, but certain normal alleles are also highly selected in Northern Europeans. Based on our observation of marked obesity in atxn2 knockout mice, we are currently examining the atxn2 gene for mutations or enriched common variants in humans with a BMI>35.
A new project in the ataxia group is the analysis of sporadic and familial ataxias in the state of Utah using the Utah Population Database (UPDB). The UPDB provides a unique resource to examine familiality of neurodegenerative phenotypes.
The Parkinson Disease group focuses on parkin (PARK2) mutations and the role of ubiquitination and ubiquitin ligases in synaptic vesicle dynamics (PI: SM Pulst). Recently, we are examining the interaction of genetic mutations and environmental toxins on cell survival (PI: DP Huynh).
Mutations in the NF2 gene are the most common cause of familial and sporadic schwannomas and are frequent in other tumors as well. Based on identification of NF2 binding partners in the yeast interaction trap, we are now examining genetic interactions of NF2 and the binding protein HRS (PI: SM Pulst).
In collaboration with Drs. Mark Leppert and Hilary Coon at the University of Utah Eccles Institute of Human Genetics, we have used the Utah CEPH families, to examine heritability of visual reaction time and visual attention. We hypothesize that understanding normal variation of attention traits will contribute to the analysis of pathological conditions involving attentional mechanisms such as ADHD, schizophrenia, and dementias. A linkage screen using the CEPH pedigrees is currently in progress.