Molecular mechanisms of pediatric neurological disease
Our research group studies both inherited and acquired diseases of the central nervous system as part of ongoing efforts to translate findings from the bench to the bedside and offer new treatments to children with neurological diseases.
Pediatric Movement Disorders and Neurodegenerative Disease
Our primary focus in the laboratory is on the molecular and cellular basis of movement disorders and degenerative diseases. At the present time, available treatments are largely focused on symptom management, and therapies targeting the underlying disease process are desperately needed.
Several basic cellular processes have repeatedly been implicated in disease pathogenesis, including autophagy as a regulator of cellular quality control, mitochondrial bioenergetics, and fundamental aspects of metabolism. We are interested in the mechanisms by which failure of these crucial cellular systems leads to disorders such as Parkinson disease. Although many proteins associated with neurodegenerative disease are widely expressed, the nervous system is exquisitely sensitive to loss of function in these essential cellular homeostatic pathways.
The genetic basis of inherited neurological diseases
The cause of many human neurological diseases remains unknown. Using next-generation sequencing technology in highly genetically-informative families, we are studying the genetic basis of spasticity, dystonia, parkinsonism, and the hereditary choreas. Using a complementary genomic approach allows us to identify new genes that, when mutated, lead to these disabling human neurological diseases. Subsequently, the availability of lymphoblast and fibroblast cell lines derived from these affected patients allows us to validate our genetic findings in vitro.
Molecular mechanisms that lead to neurodegeneration
Our subsequent efforts are aimed at understanding the factors that stem from genetic mutations and lead to brain diseases. We utilize a variety of models to dissect mechanisms connecting cellular energetics and stress-response pathways, including yeast genetic screens, knockout and overexpression systems, mammalian cell culture, and knockout mouse models. These projects complement and inform one another as new genetic discoveries are carried forward into mechanistic studies in model systems.
For more information about dystonia, click here.
For more information about Parkinson Disease, click here.
Kruer lab summer 2013:
(L to R: Anna Yarrow, Marianna Madeo, Breanna Cuka, Lauren Fields,
Tyler Jepperson, Michael Kruer, Brianna Titus)
Contact Information for Kruer Lab:
Michael Kruer, MD (PI)
Associate Scientist, Sanford Children’s Health Research Center
Assistant Professor, Departments of Pediatrics, & Neurosciences
Sanford School of Medicine of the University of South Dakota