Neuroscience research tools are incredibly powerful: Researchers can flip individual neurons on and off to observe effects at the molecular level. The problem? That’s not how psychiatric medications work, so discoveries aren’t readily transferable to useful solutions.
If Lief Fenno, M.D., Ph.D., has his way, treatments for mental illness will soon deliver a similar level of power and precision as the tools that inform them. Psychiatric medications regulate the flow of information between interconnected neurons, and Fenno’s work aims to create research tools that allow researchers to mimic the behavior and use their observations to develop better treatments.
Earlier this year, Fenno — an assistant professor in Dell Med’s Department of Psychiatry and Behavioral Sciences and the Department of Neuroscience in UT’s College of Natural Sciences — received a $1 million grant from the W.M. Keck Foundation to support his work.
“Our goal is to use bioengineering approaches to answer unsolvable problems in neuroscience and psychiatry,” Fenno says. “The tools we build are designed from the ground up to be translatable to human use as novel therapeutics — and also to be widely useful in neuroscience.”
Tell us about yourself — how do you divide your time across clinical, research and education efforts?
Clinically, I treat patients with substance use disorders (addiction) and co-occurring psychiatric illness as an attending physician at UT Health Austin and a local safety-net provider, Integral Care.
On the research side, my translational research group works across bioengineering, neuroscience, and psychiatry to develop and apply novel molecular and viral methods to delineate the relationship between neuron activity, circuit structure and behavior; translate our findings directly to human patient treatment via gene therapy; and uncover structures and activity patterns that can be therapeutically modulated using interventional psychiatric treatments. Our tools and approaches have been widely and freely distributed to public research efforts around the world.
One of the main directions we are working to solve is to bridge the gap between the power and precision of our neuroscience research tools and the mechanism of psychiatric medications. These work in very different ways, and this has limited both understanding and treating psychiatric illness.
Lastly, I take pride in my passion for teaching and mentoring at the undergraduate, graduate, postdoctoral and resident levels — fostering a culture of learning where team members are invested in producing creative, fundamental, and innovative work and develop as successful scientists.
Describe a singular memory or anecdote that guides your work today.
In college, my grandfather was diagnosed with an uncommon type of Parkinson’s disease. At some point, his doctors told us that there wasn’t anything else we could do. Essentially, we’d reached the end of what we knew scientifically and medically. This was an epiphany moment for me — the idea that there were definite, but surmountable, limits to what we know and that this directly links to how we can help patients. From that point forward, I focused on building new methods and tools and applying these to move beyond these limits and improve patient care.
If readers remember one thing about you or your area of focus, what do you hope that is?
We live in an amazing time. The pace of discovery and translation for molecular tools such as optogenetics, CRISPR, CAR T-cells, monoclonals and gene therapies have already impacted diseases that were debilitating or fatal only years ago. There is a need for applied molecular creativity to continue this pace of discovery.
Our team is uniquely positioned to move translational neuroscience forward, because we have expertise in psychiatry, bioengineering and neuroscience; our work is focused at the intersection of these three fields, which is key for discovering new frontiers in how we study and treat psychiatric conditions in a coordinated way.
