Overcoming obstacles: PhD alum Tara Tracy seeks new approaches to treat Alzheimer’s disease

January 18, 2023
Rachel Henderson

“It’s just so exciting to me — to keep trying to be at the forefront of what we can do to help people with disease.” 

Tara Tracy, Neuroscience PhD Program alum (entering class of 2004)       

Tara Tracy is an assistant professor at the Buck Institute for Research on Aging in Novato, California, where she investigates the mechanisms underlying memory loss in Alzheimer’s disease and other age-related dementias. Specifically, her lab studies synaptic deterioration in these diseases, which she hopes will lead to new ways to preserve or restore memory by repairing affected synapses.

Tracy first became interested in neuroscience as an undergraduate at Wesleyan University. She did her PhD at Berkeley with Lu Chen, who is now at Stanford. In the Chen lab, Tracy studied how synapses develop at the molecular level. She went on to do a postdoctoral fellowship at the Gladstone Institute of Neurological Disease and UCSF, where she studied how toxic tau protein affects synapses in Alzheimer’s disease.

In her lab now, Tracy combines her expertise in synapse biology with her knowledge of neurological disease to discover molecular mechanisms that could lead to cognitive decline. She says recent research from her lab suggests that there may be ways to actually repair synapses in Alzheimer’s disease. This would be a novel therapeutic approach that could lead to the development of more effective treatments.

In addition to trying to crack the difficult problem of Alzheimer’s disease, Tracy is also passionate about helping other women in science overcome obstacles in their careers. She recently founded an initiative at the Buck Institute to support and retain women in science and help them advance into leadership positions.

Read our Q&A with Tracy to learn about her research, training at Berkeley, the advantages of working at an independent research institute, and her thoughts on ways to help women scientists succeed. This interview was conducted on September 21, 2022 and has been edited for length and clarity.

Q: How did you first become interested in neuroscience?

A: I was always drawn to biology in school. But I took my first intro to neurobiology class in college. I remember [in] the first class, the professor, Dr. Allan Berlind, showed a very old video of somebody doing electrophysiological recordings on a grasshopper. There’s something about being able to record the action potentials and relate that to how these circuits in the grasshopper function — [it’s] fascinating. That really inspired me. Ever since then, I’ve really been excited about anything neuro related

Q: What brought you to the Berkeley Neuroscience PhD Program?

A: I applied very broadly for graduate school. I applied to a lot of schools, and I interviewed at a good number of schools. Berkeley stuck out to me because I liked the interdisciplinary nature of the program. I knew I was very focused on cell and molecular neurobiology, but I also wanted to learn more about the other areas of neuroscience which are also, obviously, very important. I wanted to have that basic knowledge in neuroscience — a well-rounded education — so that was very attractive to me about Berkeley.

Q: What was your experience like in the program?

A: I really liked the faculty that I interacted with. They were doing cutting-edge neurobiology that I was always interested in. That’s probably what I enjoyed most about the program.

I was in one of the first [graduate student] cohorts, maybe the third or fourth. The students who came before me were very supportive. I remember meeting them in the interviews and really enjoying my time with them and learning a lot from them, even though the program was very small at that point. So I really enjoyed that.

Headshot of Tara Tracy

Tara Tracy

Tracy and her husband Grant Kauwe, who is also a Berkeley Neuroscience PhD alum.

Also, my husband, Grant Kauwe, was in my class. We didn’t get married until after we left grad school, but we met in the program. In general, my class was pretty close. We hung out a lot. The students were all very interactive, and it’s just such a great scientific environment that fosters that. Grant works in my lab now as a staff scientist, and it has been great to continue collaborating with him after so many years.

Q: What was your thesis research about?

A: I was investigating the molecular mechanisms that occurred during synapse development. In particular, in Lu Chen’s lab(link is external) we were interested in studying the function of glutamatergic synapses, which are the majority of the excitatory synapses in the brain, and important for cognition. So we were interested in looking carefully at how these synapses develop.

What I was interested in was how do AMPA receptors play a role. [AMPA receptors are] a type of glutamate receptor at the synapse. We did kind of a simple experiment where we knocked down the AMPA receptors in developing synapses and characterized what happened to the synapses. What we found is that when we knock down the AMPA receptors at the synapse, it has some effect on the function of the presynaptic terminal, suggesting a retrograde effect.

We did a lot of electrophysiology and imaging for this study, and for me personally, what I gained from it is [understanding] just how many different ways we can assess synapse function. You can do some really nice studies to get at that. So I gained a real appreciation for the complexity of the regulation of synapses from my graduate work.

Q: What did you do after you graduated?

A: After getting so much knowledge and experience studying neurobiology, I decided I wanted to apply that to better understand what’s happening in disease. So I did a postdoc at the Gladstone Institutes [which is affiliated with UCSF] with Li Gan, who subsequently moved to Weill Cornell Medicine in New York. With Li, we were studying how tau protein becomes toxic in Alzheimer’s disease and how this toxic tau protein affects synapses and synapse biology. I think what worked really well for me is that I took all this basic biology knowledge and applied it to what’s happening during progression in disease.

Q: Did you go straight into your current position from that postdoc?

A: Yeah. I was at the Gladstone Institutes for a number of years, and at a certain point I applied for a faculty position. Again, I applied to a number of different places. I interviewed at eight places. I got maybe seven offers, and then I decided to come to the Buck Institute to start my lab here. It worked out really well for me.

In terms of my trajectory, I think I really got my solid foundation at Berkeley in terms of neurobiology. I very much appreciate the knowledge and experience I gained there. But then I learned about disease from Gladstone. So I got kind of the best of both worlds in terms of my training. Now we’re using that in my own lab, all of that. I basically have my hand in both worlds now. We’re doing some synapse biology in my lab, but most of it is focused on pathogenesis and disease and what’s happening to synapses in disease.

Q: That’s great that you got so many job offers!

A: I applied to a lot — I think I must have applied to 30 different faculty positions. I tried to pick the ones that I thought I was the most suited for; I didn’t just apply to anything. I was also selective geographically to some degree. There are certain places that I knew I wouldn’t want to move to. I’m so lucky, I’ve been in California for 18 years now. I moved here from New York City, where I grew up. I’m very fortunate that I got to stay. Another reason I stayed here is because my brother lives in the area.

Q: What are some other reasons you chose the Buck Institute over a more traditional research university?

A: I did get offers from traditional research universities, which were all great too. I think I would have been fine at a place like that. What drew me to the Buck was [that] they’re focused on aging and age-related disease, which is something I’m very interested in. So that was a good fit. I also had collaborators here that we had worked with already, and I looked forward to collaborating with them further.

Also, it’s nice that we are an institute that’s so focused and everybody has a similar interest, and yet here we are in the Bay Area where we can collaborate with other, big places. I have collaborators still at UCSF that we’re working with a lot, and Stanford now as well. It’s nice to still be in this area where we can work with the bigger places, especially for us. I don’t work with humans in my lab, but in order to do disease research, it’s really important that we apply what we’re finding in cell cultures and in mice to what’s actually happening in humans. In order to do that, we collaborate with people who do research with humans. So that’s another great thing about being here, that I can be in this small environment where everybody is interested in the same thing, but then also be able to collaborate with people at the bigger institutes that do human research.

Q: What do you do in your lab?

A: We have a number of projects. I just get so excited about more projects, sometimes I have to slow down a little bit! [laughs] I’ll just tell you about one project we’re really interested in, for the sake of time.

We’ve identified a protein (KIBRA) at synapses that’s dysregulated in Alzheimer’s disease, and we think is important for the plasticity at synapses, which is a mechanism that underlies memory formation. We found that this synaptic protein is downregulated in Alzheimer’s disease, and that this is associated with dementia. So, the model is that you have loss of this protein and synaptic plasticity is impaired, and that then could cause cognitive impairments.

What we’re working on now is can we repair synapse function, using this protein, to try to bring memory back? The thing in the disease field which is important about this is that most of the research on Alzheimer’s disease now, in terms of trying to bring things to the clinic, [has been on] how do we reduce the levels of toxic proteins in the brain like tau and amyloid beta. That’s where a lot of the focus has been on — trying to reduce these toxic proteins. Our approach would be a little bit different in that we think that you can repair synapse function, maybe, despite having the toxic tau protein in the brain. So it could repair the system without fixing the problem — that kind of approach. That’s one of the projects that we’re hopefully going to have a paper on soon.

Q: Do you have any industry collaborations?

A: I’m looking into that now. I think that’s very important, because that’s how therapeutics come to life. We’re definitely looking into that now, actively, but we haven’t gotten to the point yet where we have that in full gear.

Q: What motivates you to do this kind of research?

A: I get really excited about new ideas and cutting-edge stuff. That’s what I feel like we’re doing. It’s just so exciting to me — to keep trying to be at the forefront of what we can do to help people with disease. You know, how can we overcome the boundaries that we’ve had for the last two decades — that there’s no treatments for Alzheimer’s disease yet, really, that are very good. This is a huge obstacle and I’m motivated by the challenge of it. That’s a big driver for me in this field.

Q: For students who are considering their career options, how is working at a nonprofit research institute like the Buck similar to or different from working at a university?

A: As an assistant professor, I do not have responsibilities to teach undergraduates because there are no undergraduates here. I do teach graduate students. We have a graduate program with USC, a Buck-USC PhD program. Just yesterday, I taught a class for that program. But the teaching responsibility is very minimal compared to other places that have undergraduates. 

The other difference is that at big universities, at least the ones I interviewed at or was considering, there are a lot of administrative people to report to at different levels. Whereas here the leadership group is smaller. There are fewer people who make all the decisions, and I know them very well, and I get to talk to them. I think if I was at a bigger place, I would see those people less often [laughs] — the people at the top of the university.

My lab right now has more postdocs than grad students. That may change in the future. But we do get a lot of postdocs here at the Buck. This is postdoc appreciation week and we very much appreciate them.

We have the other things that I remember that we had at Berkeley — we have seminar series, we have meetings, we hold conferences here. So we’re very much like academic universities. Everything we do on a daily basis, other than teaching, is very similar to university life in terms of how the lab works. My lab is funded through grants, so that’s also similar.

Q: Do you have any advice for graduate students?

A: Based on my own experience, I would say follow what you’re most excited about, and keep trying. It hasn’t always been easy to get where I am. But I kept trying and learning from my mentors. One of the key factors to being able to get where I am was the mentors I had. Learning from them and having their support was incredibly important. And not just my thesis mentor or my postdoc mentor, [although] they were the most important, but other people that I knew and got to know and learn from. Seeking out mentorship from others as well — that was so valuable.

Q: Is there anything else that you want to mention?

A: One thing I really care about now, probably from my own experience, is trying to support women to climb the academic ladder. I didn’t know anything about this as a grad student — the kinds of obstacles women face — because it’s fairly equal in terms of male versus female entering graduate school. 

Tracy and her lab at the Buck Institute in summer 2022.

But then when you go up the ladder in your career, there’s a drop off [of women]. We call it the leaky pipeline. So then there’s less women in the leadership positions. 

I set up an initiative here at the Buck to support trainees and try to address the leaky pipeline. I would encourage women Berkeley students to try to seek out mentorship for this, [to] gain leadership skills that are useful in climbing the ladder. Because there are things out there that helped me, at least. As soon as I became aware of [them, it] helped me overcome some of those barriers that women face. I’ve had several ‘aha moments’ that I think helped my trajectory in terms of that.

Q: What kinds of things are you doing in your initiative?

A: We’re calling it Buck Women in Science, and we started probably six months ago. The first thing that we did was we brought in an outside person to lead a workshop on leadership skills for women. That was just to get the ball rolling. What we realized in that session was that women have all these difficulties and nobody ever talked about it. Or they can find it challenging to navigate to get to the top— there’s certain walls for women.

So then we set up peer mentoring group sessions. Once a month, we’re having these events where we choose different topics. Most recently, we’ve been discussing the book Nice Girls Don’t Get the Corner Office. I really enjoyed reading it. It’s a little bit controversial, and there are some things in there that may not be useful. But we had some great discussions about these things — how to not be a ‘nice girl’ because it can sometimes backfire. At least I know I’ve struggled with some ‘nice girl’ attributes in trying to get to a leadership position. And then corner office means your top-level dream job, whether it’s in academia or not.

We actually had so many things to discuss in the first session that we made a second session to talk about more things. We now have a list of topics that we’re going to be talking about at these sessions, including: networking skills for women; managing up; impostor syndrome; how to ‘have it all’ — managing different aspects of your life; what are women leaders — how do they act, look, and sound? All of these kinds of things.

Then we’re going to invite speakers. We got some funds from our CEO to invite speakers for our group — well-respected woman scientists who will visit and give scientific talks, and share some tips with our group on how to climb the professional ladder. My old classmate, [Berkeley Neuroscience PhD alum] Emily Jacobs from UC Santa Barbara, will be visiting us soon to give a seminar for this. I’m really hoping this kind of support group can help people learn skills.

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