A CUNY Neuroscience Professor and His Students Seek to Bring Relief to Parkinson’s Disease and COVID-19 Patients

Professor Andreas Kottmann (third from left) with students and alumni from his lab (l to r): Ph.D. student Santiago Uribe-Cano (Psychology); alumna Lauren Malave (Ph.D. ’20, Biology); Ph.D. student Dustin Zuelke (Biology); master’s student Sonia Bernal (Cognitive Neuroscience); and alumnus Lev Starikov (Ph.D. ’19, Biology). (Photo Courtesy of Andreas Kottmann)

By Lida Tunesi

In a recent study published in Communications Biology, researchers from the lab of Professor Andreas Kottmann (GC/City College, Biology) discovered new information about the action of a cell signaling protein called sonic hedgehog. Their work may offer hope for Parkinson’s disease patients who suffer from a common side effect of dopamine replacement medication, one that can either be an inconvenience or get so bad as to be incapacitating.

“There are a few years where dopamine replacement works like a miracle,” Kottmann said. “But after a couple of years there’s this side effect that manifests as uncontrollable, dyskinetic movements. They can be so debilitating that at some point patients cannot bring a glass of water to their mouths or feed themselves.” 

Kottmann, who is also an associate professor at the CUNY School of Medicine at City College, also researches questions about what happens in our brains when we learn new skills, questions which are biologically tied to his work around neurotransmitters involved in Parkinson’s disease.

The Graduate Center spoke with Kottmann about his lab’s latest research, new directions, and his collaborations with diverse student researchers.

The Graduate Center: Generally speaking, what does your lab study?

Kottmann: The goal is to understand model-free learning, which is learning when you don’t know what you have to learn, or learning by trial and error. You have to do something 10,000 times to become really good at it, but you are not really aware of what happens in your brain from one repetition to the next. We aim to visualize the incremental changes during these trials and errors.

There are also associated questions. Can you become expert in many motor skills, or do you run out of space in the brain? I think there’s good reason to believe that there are mechanisms in place that allow you to refine these motor skills over and over again and become expert in many skills. The challenge is to see what molecules and biochemical pathways are involved. We know there’s an area in the brain that’s involved called the basal ganglia, and if the basal ganglia are affected, the consequences are severe. Parkinson’s is a disease where the basal ganglia are affected, and it’s characterized by slowness of movement, rigidity, and reduced ability to learn new motor skills and refine those skills. That pointed early on to involvement of dopamine neurons, so what we understand now is that dopamine is important for model-free learning.  

GC: Does your group have specific research priorities for the coming year?

Kottmann: We have two prongs, and one is COVID-19. It has become clear that there are neurological complications that people with COVID-19 suffer from. The most severe complication shows many overlaps with Parkinson’s disease, and that made us very interested. Right now, we are testing and following up on some preliminary results that we got a couple of months ago that the spike protein on the virus interacts with neurons in the basal ganglia. We want to understand what it does. There’s an opportunity for us to conduct research that relates to the Parkinson’s studies and at the same time an opportunity to learn something completely new. We believe this will allow us to test, as soon as new variants are isolated, their strength or propensity to affect basal ganglia function compared to other variants. This doesn’t help to prevent the disease, but it might help to allocate appropriate resources or advise patients about possible neurological sequalae.

The other prong is linked to the results of our new paper. We use the dyskinesia complication in Parkinson’s to really show that the sonic hedgehog protein acts as a classic neuromodulator, to show that it has a function. Now the question becomes: How does that relate to learning? The indication from our paper is that sonic hedgehog counteracts dopamine, that it keeps dopamine in check. There is a lot of work to be done in regard to the question of whether the resource that lets learning happen is limited. We want to test whether sonic hedgehog might provide a mechanism that replenishes new substrate, makes new synapses and structures upon which reinforcement learning can be encoded. Dopamine does the opposite; it strengthens synapses that were associated with good outcomes. But this also reduces the complexity of the brain. You don’t want to be able to hit a baseball but not do anything else. We have a couple ideas of how to test whether sonic hedgehog makes new synapses.

GC: Two of the authors on the new paper — alumna Lauren Malave and Ph.D. student Santiago Uribe-Cano — are RISE fellows. What can you tell us about the RISE program and your connection to it?

Kottmann: In the time that I’ve been at CUNY I have had five graduate students in my lab, and everything we achieve is really because of the students. These two became RISE fellows. It is a program set up and supported by the NIH to support students with a stipend, tuition, and costs of living. I am a mentor within that program, but not the principal investigator. At CCNY, the people who actually hold these grants are Dr. Mark Steinberg and Dr. Ruth Stark. We’re very happy and fortunate that graduate students from my lab were chosen by an internal selection committee process at CCNY to be funded by these grants. Lauren Malave won the Professor Josh Wallman scholarship award from City College for her research, and much of the new paper is really her thesis.

GC: What advice can you offer current graduate students who are starting to think about their career and look for post-grad jobs?

Kottmann: I think it’s important for any student to think they are not in isolation in this game. It’s important to network and have a support system — this allows them to make that next step in their career. What we try to do in the lab is make sure students are mentored and supported, and not just by myself. We try to put together advisory committees early on in the process that can really help the students hands-on. They can check on what I suggest and what the students want to do, and we discuss these various possibilities. I try to put together these committees with a view to help the students find good jobs, either in academia or elsewhere, to help connect them with a larger group of supporters.

GC: Your lab has a nice mix of undergraduate, master’s, and Ph.D. students. What do you like most about working with students?

Kottmann: I’m so impressed by the graduate students. It’s amazing. They all come in with tangible life stories, they’re highly motivated and they’re hard working. They run the lab. 

Science is not done in isolation. It really depends on people working together. The greater the diversity, I think the better the ideas that come out. That’s diversity in all aspects — socioeconomic, ethnic, and also levels of understanding. Having undergrads in the lab sometimes can be a distraction, but at the same time offers grad students a chance to hone their skills in explaining things. If you explain something and receive resonance, then most likely you understand it yourself. And that is true at any level of expertise and career. In our lab we strive to create a safe space and an intellectual environment in which everyone, from summer students to principal investigators, feels comfortable to contribute their thoughts to solving exceedingly exciting and important puzzles that nature presents us.

Published by the Office of Communications and Marketing.

Submitted on: SEP 29, 2021

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