Faculty Spotlight: Associate Professor Gene Gurkoff, PhD

As interviewed by Gabriela Lee

Dr. Gene Gurkoff is an Associate Professor in the Department of Neurological Surgery, Affiliated Faculty with the Center for Neuroscience, and Affiliated Faculty with the Center for Neuroengineering & Medicine.

• Tell us about your background.

As early as high school, I was really fascinated by how the brain worked, but perhaps even more curious about why it often didn't work. Partially because my dad was a psychotherapist, I became aware about psychiatric diseases, such as depression, that we didn't know why people had them, and no idea how to treat them. Then, the summer after my first year in college, I was able to get a job with a friend's father, who worked at a startup biotech. The company was researching a drug for a skin disorder called scleroderma, and a I learned a few things from that experience. I realized that I really enjoyed being in the lab, even though it was a protein chemistry lab. Perhaps even more importantly, I really enjoyed the people I was working with. These were just really smart people who were tackling a very important problem – and enjoying their jobs! But it wasn't all science all the time: they made a point of having a regular lab lunch, and we had wide ranging discussions about everything from science to pop culture.  It was such a great experience that I continued in this job for a second summer. At that point however, I knew I was not a protein chemist and that it was time to begin my path towards being a neuroscientist.

In my junior year at Brown University, I joined the lab of Dr. J. Michael Walker. His was a chronic pain lab and I really liked it. I had gotten into neuroscience to study neurological and psychiatric disease. In fact, my mother had considerable experience with chronic pain. While this was enough to motivate me to join the lab, it was my mentor, Mike, who challenged me to be a skeptic, to push my limits in the lab and ultimately encouraged me to consider graduate school as an option. I remember being filled with imposter syndrome, and then Mike told me that he had no doubt, and that if I wanted, he would take me into his lab. I initially only applied to two of the top five schools in the country as I was busy with being a college student and didn’t allocate enough time to research PhD programs. I didn't get in. Perhaps this is one of my first life lessons as a scientist. Fail. Get back on your feet and try again. I found a job in Dr. Allan Basbaum's lab at UC San Francisco where I continued to research neuropathic pain lab for two years. These extra years confirmed both my passion for research and the laboratory environment, and also that I really enjoyed working with people who were smarter than I was.

I applied again for graduate school and got into UCLA. Initially I was lost. There were so many great labs and I didn’t know how to choose what to do. During one of my ethics classes in spring quarter, I met Dr. David Hovda, a professor who studied traumatic brain injury, and I realized from a couple of short conversations that he was also going to be an exceptional mentor for me. He had a passion for science. He also had a sense of humor. In my first week in the lab he paired me with a new junior faculty, Dr. Chris Giza. Dr. Giza is a pediatric neurologist and, like Dr. Hovda, a true mentor. Both encouraged my curiosity, and really shaped who I was as a scientist. Also, by working for two mentors, one a PhD and one an MD, I had my first real experience of translational team science: people with different training, coming together in the laboratory to solve an incredibly challenging clinical problem.  To the dismay of my mentors, for the first half of graduate school, I was intent on going into big pharma. I thought that I could harness my understanding of mechanisms of neurological disease and try to develop novel therapies. I had learned by this point that I really struggled around patients, focusing on the sick and dying rather than relishing in the treatment. But I still wanted to be on the front line of solving important clinical problems. As I progressed, I realized that the most important aspect of my training was my relationships with my mentors – going all the way back to Dr. Walker – and that I really loved students and mentoring in particular. The only way to mentor many students is to be in academia. So, I changed my goal.

Starting in my second year of graduate school, I made a point of networking at conferences. It was very uncomfortable at first, but after three years I found that I had met a lot of wonderful traumatic brain injury researchers. In fact, two of the first people I met at a research conference were Drs. Bruce Lyeth and Robert Berman from UC Davis. I made sure to catch them at their poster or talk every year, and eventually I pursued a post-doc with Dr. Lyeth. While Dr. Lyeth was my primary mentor, I again benefited from being placed in a collaborative work environment. In the neurological surgery labs I learned a lot not just from Dr. Lyeth, but also Drs. Berman and Schwartzkroin (a world renowned epilepsy researcher). I was also fortunate to be a part of the NSF-funded UC Davis Center for Biophotonics Science and Technology. It was through the Center and the guidance of Drs. Steve Lane and Dennis Matthew that I actually started working with engineers and physicists on team science projects. I brought my neuroscience to the table, they brought their knowledge about using light to study biology. I was also partnered up with Drs. Anna Corbacho and Marco Molinaro in the education programs of the center. I had the good fortune of getting to help develop curriculum for summer programs and to work with students who were transferring from community colleges into UC Davis. It was the combination of all of these wonderful mentors and opportunities that enabled me to grow as a scientist, develop my research niche and also demonstrate my ability to mentor students. It turns out I was in the right place at the right time, as we needed new faculty in the Neurological Surgery Department right about when I was ready to take the leap and start a job search. I have been on the faculty here ever since, studying traumatic brain injury and epilepsy.

• How did you get to your current research field, which includes neuroengineering? 

My early career had largely been based on pharmacological interventions when one day, my clinical colleague Dr. Kia Shahlaie, now Professor and Interim Chair of the Department of Neurological Surgery, came down to the lab and said that we should do research in neuromodulation and specifically deep brain stimulation (DBS). Neuromodulation is the targeted delivery of therapy, specifically delivery of an electric current, or even a drug, to a specific location in the nervous system. This is in contrast to most therapies which are given systemically and therefore interact with targets throughout the body. I was really hesitant to take that plunge because we didn't have a mechanism, i.e. a good understanding of how neuromodulation was even working. Sure, stimulators were helping people with Parkinson’s disease, and a recent publication described exciting outcomes in a traumatic brain injury patient who had been minimally conscious prior to the DBS treatment. But it felt like magic. All of my mentors had trained me to be skeptical, to avoid research that was too good to be true, and to really look before I leapt to a new research area. 

Dr. Shahlaie sent a neurosurgery resident, and then another, down to the research lab. The goal was to start recording neural activity after injury and while rats were doing behavioral tests and to determine whether we could identify a mechanism and therefore a target. And what that required me to start doing is thinking along the lines of neuroengineering for the first time: how to decode neural signals. But once we decoded neural signals, do we have a device for actually intervening or do we need to design a new device? And I realized I needed to form new collaborations, and get to know people who do things like building devices and coding, i.e. get into what is now known as neuroengineering. What resulted was a team of Dr. Shahlaie and myself, working with a resident Dr. Darrin Lee, and a collaborator in the Psychology Department, Dr. Arne Ekstrom. Once again, I found myself enmeshed in team science.

We tried some very preliminary experiments in our lab where we put a deep brain electrode into a rat that had traumatic brain injury and recorded theta oscillations. Theta oscillations are an electrical signal that results from the coordinated activity of hundreds or thousands of neurons that are aligned with an electrode. When rats, and also humans, navigate, slow wave theta oscillations can be observed in structures related to learning and memory, like the hippocampus. Initial experiments suggested that oscillations were altered for an extended period of time after injury. We scoured the literature and found experiments older than I was that told us exactly how we might drive these theta oscillations. We implanted an electrode and turned on the stimulator. It was almost like magic. I wasn’t sure why it was working but we consistently saw improved outcomes in our rats, which meant that we actually had to take this seriously - there might actually be something to the science. What was challenging to me is this meant that I needed to understand better how we record neural signals which means learning about amplifiers and circuit boards. I had to understand how to decode neural signals, which are oscillations that come from the sum of activity of many neurons. And I needed some expertise in physics or math, to design a code that can extract information from neural signals. More team science!

The nervous system is complicated, with lots of different regions. We needed to start thinking of it in terms of models: how do you model out the normal circuit, the broken circuit, and then what are we modulating with our deep brain stimulation? I had none of the needed expertise. Neuroengineering provided me with a space where faculty with different backgrounds and expertise could come together - somebody who understands modeling, somebody who understands circuits, somebody who understands time series analysis, which is the analysis of EEG, and I understand neuroscience and traumatic brain injury. We all bring our expertise and experience to the table to be able to address hypotheses that we wouldn't be able to address on our own.

• What motivates you? 

Therapies developed over the years for neurologic disorders work for some people but not for others. It is like a rule. It is as true for depression as it is for chronic pain or epilepsy. In addition, even the therapies that do work frequently have negative interactions on other domains such as sleep, cognition, depression - undesirable side effects. For some neurologic disorders, like traumatic brain injury, we don’t have any effective therapies. We need to fill all these gaps.

One thing I came to realize from collaborating with my clinical partners is that the vast majority of therapies are designed to target a primary morbidity. Seizures for epilepsy. Motor control for Parkinson’s disease. Social behaviors in children with autism. However, while we all think of Parkinson’s, for example, as primarily a movement disorder, these patients typically also have cognitive problems, sleep disturbances, and/or emotional and depression issues. These are all secondary to the movement disorder - comorbidities. Another example: in epilepsy, seizures are the primary morbidity. Similar to Parkinson’s disease, many of these patients also have sleep, cognitive, and mood disturbances. When discussing with my colleague Dr. Shahlaie, we saw the opportunity: Could we come up with an innovative therapy that targets the primary morbidity, but also improves some of the other problems patients have with sleep, cognition, depression? If so, we could impact the quality of life of many patients. Going all the way back to my time as an undergraduate student, here was an opportunity to have a real impact on treating patients with neurological and psychiatric disorders, without having to be the one actually treating the patient!

This was something we thought we could do in the lab and focus on as our research niche. Since cognition is a huge problem across many neurologic disorders, and since improvements can make a huge difference for patients and their families, we decided to look at improving cognition as a common endpoint after neuromodulation treatment.

My initial skepticism arose from the fact that as a basic neuroscientist or a graduate trainee, we're taught that our research has to identify the mechanism of a therapy. With Deep Brain Stimulation, you're putting an electric field into the brain, which has the potential to activate or inhibit all the cells in that area, with no specificity to one cell type or another. Furthermore, electricity travels to other areas of the brain, beyond the targeted area. Therefore, we know that there are multiple mechanisms at play. I think neuroengineers are trained differently: they look at how to solve problems. Meeting other people who appreciated what we were doing and why was really helpful and made for productive collaborations. I realized early on that our focus area is inherently a team science - based problem. This is very exciting because I greatly enjoy collaborating on projects. I’ve learned a great deal about electrophysiology and analysis of electrophysiology data from colleagues in my network. Some of my grant funding was contingent on identifying scientists, such as Dr. Ekstrom, with the right expertise before reviewers believed that I could run the experiments that I had proposed.

Neuromodulation has advanced a great deal since I started in the field over 10 years ago, and there's a lot more emphasis on using closed loop stimulation, which means recording neural activity and then stimulating in response to that activity in real time. For example, using neural signal to detect the start of a seizure before stimulating, rather than having the stimulator on all of the time. This means not only do you have to analyze your recordings but you have to decode neural recordings in such a way as to feed back signals into the system to stop the seizure, which requires new devices that can actually take advantage of all the new information we're gathering. I realized it was even more important for me to be a part of a collaborative community and be surrounded by all this expertise because there's no way to solve this problem in a single neuroscience lab. This is why I was one of the first people to sign up to participate in a new Center for Engineering and Medicine at UC Davis, so that I could make the necessary connections to do the complicated team-based and cross discipline-based research that is going to take preclinical research into the future.

• What would you like to see the field achieve in the next 5-10 years? What is your dream?  

First, I want to see even more emphasis on team science. We're starting to see that pendulum swing where more grants and projects encourage or even require team science. There is increased recognition that we need to have diversity of all kinds: ideas, people (racial diversity, socio-economic, cultural), technologies – and we all bring different things to the table. In addition, more partners at more campuses should lead to better reproducibility, which is a known challenge with preclinical work. Exciting findings are challenging to reproduce across research campuses. The more we know about the brain and how complicated it is, the more it’s obvious that there's no way we're going to solve big problems without diversity of skills and ideas. I really do want to see the field move toward even more team science than it already has.

Second, I’d like to see the field stop focusing on techniques so much and instead think critically about the quality of the scientific question and the intellectual contributions to solving scientific challenges. We are always excited about new tools and what knowledge they can unlock. But if the hypothesis isn’t strong, or the experiment isn’t well thought out, then a tool is just a tool.

As for the science, my dream is to be able to record and decode neural signals from across multiple regions of the brain, as opposed to single regions. We can do that now in a rat, and also in humans using electroencephalography (EEG), but the devices and strategies that are really going to change the ways we treat patients are still 10-20 years away. We have started modulating single regions, understanding the neural circuits, and developing the necessary technologies to move to multiple regions. We will need to develop new biocompatible materials, and devices that have sizes and shapes specific for the target application. And we need more sensitive tools to measure recovery of function. We will need to optimize targets and stimulation parameters. We will need to align many partners: researchers, clinicians, patients and their families. There is movement across all of these fields now, it just takes time to integrate all pieces into coherent studies.

What is fascinating about neuromodulation for treating epilepsy is that the efficacy of the neuromodulation improved with time, which means it leads to fundamental changes in the nervous system. Electrical stimulation seems to modify neural circuits. We were able to observe this by looking at data collected over more than 15 years. It takes a lot of time to get the data, go back to the patients and see what changes to the treatment are necessary so that their cognition is not adversely affected, then implement the changes and collect new data. The generation of scientists before us benefited from the work of their predecessors and now it’s our job to move things forward. And I think that's one of the strengths of the Center for Neuroengineering and Medicine, as it facilitates team science and interdisciplinary training of our students, for an environment where we integrate diverse expertise and we ask the right questions from the start.

For my career, my dream is to continue doing research in areas I’m passionate about, collaborate with colleagues as we work on challenging issues that affect patients, and to be a great mentor. I would love it if my research would contribute to improving the quality of life of a patient one day – that would be the cherry on top. However, I know that hundreds of clinical trials fail and still, we learn something from every clinical trial. Finally, there is only so much any one of us can accomplish as an individual. Perhaps my greatest contribution is training dozens of students, with my first undergraduates from 15 years ago becoming clinicians and researchers, nurses and teachers. My first graduate student is taking his first faculty position. I think everyone knows that saying: “It takes a village.” I have been so fortunate to be a part of an amazing research ‘village’ and to help grow it over the course of my career.

• What advice do you have for students interested in neuroengineering? 

My advice for students at all levels is to always put yourself in the best position for success. That means you have to do reasonably well in school, and more than ever before, it’s important to be able to work well with others. Be nice and be a team player, so that others want to work with you.

If you're truly interested in solving a clinical problem, you need to work with clinicians, talk with patients about what they're experiencing, and ask the patients what's most important to them. For example, we always assume that in seizure disorders eliminating the seizures is most important. If they seize they might fall. If they have spontaneous seizures, they lose their drivers license. However, it turns out that some patients are more interested in getting a good night of sleep. Antiseizure medications work for some people to reduce their seizures, but 25% of the patients stop taking them because they change their mood or cognition, or they exacerbate comorbidities.  I think to get to the right questions, we have to have all of the stakeholders stay involved, which means patients, families, clinicians, and the scientists coming together.

For the last several years I’ve led a career development class in the spring for the neuroscience graduate students where I invite people from different career tracks for informational interviews, where they talk about their professional paths and answer questions from students. Speakers come from academia, community college, tech industry, writing, finance, government, and they are mostly UC Davis alumni. Every single speaker mentioned serendipity: they were at the right place at the right time. If you put yourself in a good position, and you are following your interests, something will leap out. You just have to have confidence that you put yourself in a position to succeed and you make decisions as they come and then you just trust yourself. If you are honest with yourself about what’s important to you, and what the metrics are for how you measure your quality of life, you can then choose a path that resonates with your values. Follow the well-known advice to get to “know thyself”, and build it from there.

I have a lot of trainees who worry that they don’t have enough neuroscience background. You can be an economics major, and succeed in neuroscience graduate school. It takes a little extra work to get caught up, but there are many tools, and so many good teachers out there that one can get caught up rapidly. The key is to find something you enjoy and do it really well and enjoy doing it. Careers, scientific or other, are filled with challenges and failure. If you don’t love what you are doing, how will you manage these challenges? You must follow your passion!

Moreover, develop some routines and good habits. In my freshman seminar, “Brain Stimulation” I try to teach the students that the best way to stimulate your brain to maximize your potential is to eat well, sleep well, exercise, have a hobby, and spend time with your friends. Getting your mind and body right activates your brain and puts you in the best possible position to succeed. Finally, stay true to yourself, and follow your passion.