The missions of the Cowell lab originate from Dr. Cowell’s inherent interest in understanding the biology underlying severe neurological and psychiatric disorders which impact one’s personality and daily living. These disorders take tremendous financial and emotional tolls on patients and their families. Family members and close friends of Dr. Cowell have suffered from these types of disorders.
ONGOING WORK IN THE LAB
The majority of the work in the Cowell lab attempts to elucidate the basic mechanisms of transcriptional regulation for gene programs for mitochondrial and lysosomal biogenesis in neurons using mouse models and mouse and human transcriptional and proteomic datasets. This information is then utilized to understand how neurons become vulnerable to age-related dysfunction and death in movement disorders. Neuron types of interest include:
● Dopaminergic neurons of the substantia nigra (Parkinson Disease)
● Glutamatergic neurons of the cortex (Frontotemporal Dementia and ALS, Parkinson Disease, and Huntington Disease)
● Striatal spiny projection neurons (Huntington Disease)
Much of the lab’s work has focused on determining the roles for the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1á) in gene regulation in neurons, with the recent shift to exploring the roles for members of the estrogen-related receptor (ERR) family in PGC-1á-mediated gene regulation. As agonists and antagonists exist for the ERRs, it is possible that PGC-1á-dependent transcriptional programs could be activated or enhanced with ERR modulators in neurodegeneration.
In light of the profound mitochondrial dysfunction in movement disorders such as Parkinson Disease and Huntington Disease, the Cowell lab has been exploring ways to utilize our knowledge of PGC-1á-ERR pathways to enhance neuronal survival in mouse models of these disorders. Recent work from the lab has demonstrated that overexpression of ERRã can delay dopaminergic neuron terminal and cell loss in a synucleinopathy model; future goals include improving our understanding of the best way to enhance PGC-1á/ERR signaling in neurons in vivo.
Considering the lab’s expertise in neuroanatomy, neural circuitry, multi-label fluorescence in situ hybridization and immunofluorescence, Dr. Cowell and members of the lab often collaborate with other labs to provide experimental planning and/or technical assistance with these approaches. Also, Dr. Cowell’s extensive expertise in many rodent models of neurological and neuropsychiatric disorders has been recognized by inclusion as a grant reviewer, pharma consultant, and drug discovery consultant for a number of colleagues and grant funding institutions.
