Neuromodulation

The brain is a network, and as we learn more about the pathophysiology of neurologic diseases, it is increasing clear that they are not isolated to a specific brain region but emerge from a dysfunction in brain networks. Many diseases are also a direct or indirect result of inflammatory events both in the brain and systemic. Indeed, epilepsy, Alzheimer's disease, Parkinson’s disease, neuropathic pain and depression all exhibit loss of neurons and reduced neuronal density as well as altered connectivity of key regions, and in many cases, the hallmark of inflammation is coincident with such neuronal death. As we begin to identify some of the circuits common to pathophysiology of many of these diseases, we can take advantage of new, minimally invasive, highly targeted interventions, such as neuromodulation, to help treat patients with debilitating symptoms but no cure. We are focusing on two quite distinct neuromodulatory pathways: (1) magnetogenetics and (2) control of circadian rhythms, both that can address potential therapeutic modalities in the future. However, our studies to date remain focused on gaining a mechanistic understanding of these two areas of neuromodulation. 

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Projects

As many essential elements of the immune system undergo circadian oscillations, a mechanism behind the relationship between circadian disruption (CD) and increased rates of Alzheimer’s disease and related dementias (ADRDs) could stem from dysregulation of circadian inflammatory responses. We are investigating the interplay between CD and macrophage/microglial activation into pro-inflammatory states, which could lead to increased oxidative stress in the central nervous system and increase the likelihood of neurodegeneration.
We are combining nanotechnology and bioengineering to demonstrate that external and internal, genetically-encoded nanoparticles can be used in vivo to remotely regulate cellular activity. Calcium channels are of great therapeutic interest due to their numerous and varied functions throughout the body. One important channel, transient receptor potential vanilloid 1 (TRPV1), has gained great interest throughout the literature since its discovery.
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