Kosaka Top Basic Science Award Winner: Andrew McKinstry-Wu, MD

Consciousness and reversible unconsciousness first drew Andrew McKinstry-Wu, MD, to the field of anesthesiology. Now 13 years after he began his residency at Perelman School of Medicine, University of Pennsylvania and later his practice and research, he was recognized for his hard work studying this very topic area. Assistant Professor of Anesthesiology at University of Pennsylvania, he was selected from a competitive field of abstract applicants as the Kosaka Top Basic Science Award recipient at the IARS 2022 Annual Meeting for his research on “Glutamatergic and Adrenergic Neurons Mediate Alpha-2-Agonist-Induced Sedation and Hypnosis in Mice.” In the following Q&A interview, he shared some of his insights into his investigations and hopes for the future.

Abstract Title:

Glutamatergic and Adrenergic Neurons Mediate Alpha-2-Agonist-Induced Sedation and Hypnosis in Mice

For this research, you are:

Principal Investigator

How long have you been at this institution?

I began residency at Penn in 2009, so including residency, 13 years.

Do you conduct your research by yourself or with a team?

There’s almost always a team. I couldn’t have done this work without the help of my research techs, Nathan Frick and Paula Kwasniewska, my collaborator, Steve Thomas, and my friends and mentors Max Kelz and Alex Proekt.

What drew you to this area of research?

I was drawn to anesthesiology as a field by a curiosity about how drugs are able to produce reversible unconsciousness, and, in turn, identifying the requirements of the brain for consciousness that these drugs are altering. Alpha-2 agonists sit at an intersection between two types of reversible unconsciousness, anesthesia and sleep. More broadly, adrenergic signaling and circuits offer a window into both sides of the coin of arousal and hypnosis, as adrenergic neurons are involved in both processes.

What is the goal of your research?

This project’s aim was to identify the neural population on which alpha-2 adrenergic agonists directly act to produce sedation and hypnosis.

What’s the most significant finding?

Interestingly, both adrenergic and glutamatergic (expressing the Vglut2 promoter) neurons are directly acted on by alpha-2 agonists to produce sedation and hypnosis, and eliminating that direct effect by knocking out alpha2a adrenergic receptors in either of these two neural populations blunts or eliminates the sedative-hypnotic properties of alpha-2 agonists.

Will your findings directly impact patient care? If so, how?

Ultimately, understanding the neural circuitry capable of producing hypnosis will have applications in both anesthesia and sleep medicine – this is an early step in that endeavor.

How has the COVID-19 pandemic affected your research and work over the past year?

It’s been tough. We had some serious setbacks early on in the pandemic as we lost some mouse lines due to facilities being inaccessible. It probably put us back 6 months or more.

How has COVID-19 changed your learning/education needs?

I can’t say that it has? I’ve appreciated the increase in flexibility offered by some of the online resources, but I don’t think it has changed my needs, per se.

How do you feel about receiving the Kosaka Best of Meeting Award?

I’m quite flattered that my work was chosen from among a really fantastic array of research.

Do you think this award will affect your research/professional trajectory? If so, how?

I’m looking forward to new collaborations and conversations that this award has helped to usher in through the promotion of my research.