The Hepler Lab

The Hepler lab studies how brain cells communicate with one another to modulate synaptic signaling and brain physiology.   To do so, our lab employs a variety of modern multidisciplinary experimental approaches including cellular signaling and imaging, molecular biology, protein biochemistry, bioinformatics/genomics, proteomics, and genetic mouse models.

More specifically, our research focuses on identifying key brain signaling proteins (RGS proteins, G proteins, receptors and linked signaling proteins) to understand how these proteins work together to propagate neurotransmitter and neuromodulator signals to regulate neuronal and glial functions.   These cellular functions are critical for normal cognitive functions, learning and memory as well as tissue regeneration following brain injury (e.g., stroke).  Impairment of these processes contributes to cognitive decline associated with neurodegenerative diseases (e.g., Alzheimer 's disease and others) and aging.

Current research focuses on identifying roles for RGS proteins and their binding partners in regulating synaptic signaling and plasticity in neurons as it relates to learning and memory, reward/addictive behaviors, and neuroprotective roles in response to seizure activity. Complimentary studies focus on identifying human mutations and genetic variations within the RGS protein family relating to variable human traits and disease states. Ongoing work seeks to determine the functional consequences of de novo RGS protein variants/missense mutations with the goal of understanding the impact of these protein variants on physiology and disease.   Relating to this, we also seek to define the functional consequences of genetic variation in the general population by identifying RGS protein gene regions intolerant to change, and identify candidate genes that contribute to multifactorial human traits and as risk factors for diseases. This information will help guide our efforts and those of others in the development of new small molecule inhibitors or mimetics of RGS protein functions that will dissect/define RGS roles in cell physiology and serve as lead compounds for future drug development. 

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