Episode 21: Elva Diaz, PhD

The following interview was conducted in-class, during the Spring 2024 session of Hidden Figures: Brain Science through Diversity, taught by Dr. Adema Ribic at the University of Virginia. What follows is an edited transcript of the interview, transcribed by Astrid Ouazana, Bibby Kittrell, Christian Duong, Irelyn Hearn, Jasmine Singh, Lauren Wisniewski, Madelyn Reddan and Nour Bensadik, who also drafted Dr. Diaz’s biography. The final editing was by Dr. Adema Ribic.

Dr. Elva Diaz completed her undergraduate in Biochemical Sciences at Harvard College, then continued her studies at Stanford University where she received her PhD in Biochemistry. Dr. Diaz then completed her postdoc research in Developmental Neurobiology at UC Berkeley. Her research interests include molecular mechanisms of excitatory synapse development, function, and plasticity in the CNS. Dr. Diaz currently researches molecular mechanisms of neural development using a rodent model system at UC Davis where she also serves as Professor in the Department of Pharmacology and the Chair of the Neuroscience Graduate Program.

How did you get into the field of neuroscience? Specifically what drew you towards neural development? And how it has shaped your career?

My undergraduate training/degree is biochemistry and as a PhD student I studied molecular and cell biology. I came to neuroscience later when I attended a scientific conference that was called Cell Biology of the Neuron. It was there that I saw this cell (hippocampal neuron) for the first time. I was presented with research talks that showed lots of images of neurons and I was simply blown away by the fact that this was one cell within our brain that could potentially be contacted by so many other cells in our brain. At that time I was a PhD student and then for my post-doc I decided to move into neuroscience. I’ve never taken any formal neuroscience classes. I audited a class as a post-doc, I went to meetings, I read literature and textbooks to get the training in neuroscience.

Are there any other kinds of turns or challenges that you experienced and how did you handle them?

The challenge and excitement of research careers is that sometimes it’s not clear what the answer is, because you are the one who is trying to figure it out. You can’t go to a textbook and look something up. That is always the thrill of the discovery, but also can be quite difficult. It’s as if you’re reading a textbook and you get to chapter 10 and it's all blank. As an undergraduate you are really good at reading the textbook, and you have your study habits and things like that to understand facts, and then you get to a blank chapter. And then, what do you do? That part is always what took me a while, I would say. As a PhD student, to make that transition between focusing on learning facts and the discovery of new knowledge, and how to structure your time and critical thinking towards that end.

What do you consider to be the biggest accomplishment in your career and how did you work to achieve it?

When I was a high school student I loved science and math. I loved those and they were my favorite subjects. I also liked English but I was just not as good at it. I also had no idea that you could do research as a career. With science and math I always said, “Okay, I guess I'd have to go to medical school.” That's all I knew that you could do if you liked science. And I think my biggest accomplishment or what I'm most proud of is when I went to college, having no clue that you could do a research career, I spoke with - and I still remember to this day - my research or academic advisor as a freshman. I explained how I liked math and science and that I was going to major in biochemistry, and assumed I'd go to medical school. And she asked me “Well, have you considered a graduate school?” I said, “Oh! What’s graduate school?” And she said, “Well, you do research, and you obtain a PhD.” And I said, “Oh! What's a PhD?” To this day I'm really struck by the fact that I had no idea what a PhD was. I had not had any contact with anybody who had a PhD in high school. I knew lots of doctors, medical doctors, but no one was a PhD. Then she explained to me she was actually a PhD student in English, and she introduced me to a friend of hers who was a PhD student in biochemistry. I remember distinctly him showing me a gel with DNA on it, and I was just like “This is amazing!”

Did you try to pursue research as an undergrad?

Yes, but I didn’t know how to. There was no Internet then and I had to call people. I had to go to people's office hours and try to get research experience. I had to figure out what you had to do to get into a PhD program, without the Internet. I wrote to a lot of schools and asked for information about their programs and things like that. That is one of my biggest accomplishments, the fact that I was able to do that without any prior knowledge.

You have conducted prior research with pluripotent stem cells and you received the NIH Director’s New Innovator Award for your research with these stem cells and pediatric central nervous system tumors. Where do you see research going with these pluripotent stem cells and immunotherapy in our lifetime, in our generation, and where would you point students like us to consider research in this area?

This project started in 2009. There are therapeutics that have been FDA approved that basically utilize this type of approach where you can isolate the blood cancers, reprogram the cells, and then you can replenish them back to the individual in order to try to combat some of these blood cancers. The brain tumor continues to be a challenge to this day. The accessibility of the tumors within the brain is one difficulty. The one thing that’s new since then that has come up specifically for these brain cancers is that the cells within the brain tumor themselves actually form pseudo synapses with our central nervous system. They do this as a way to obtain nutrients, to obtain electrical activity, to trick the brain into thinking that these tumor cells are actually part of the existing network. I think that a future therapeutic is to see if we can identify inhibitors of those pseudo synapses in order to try to target those particular cells.

Some of your lab findings have shown gene misregulation can lead to diseases such as brain tumors, substance use, and schizophrenia. Do you think that these effects can be reversed by doing something like deleting parts of the genome, or that they are permanent problems that cannot be reversed?

There’s promise with the advent of technology like the CRISPR gene editing. There’s the potential now to be able to try to edit genes that are either mutated, or say, are shut off when they’re supposed to be expressed, or things like that. Again, it’s always going to be a challenge when trying to do that in people. The more traditional approach would be then to try to find small molecule chemicals that will either boost activity of your protein of interest or inhibit mutant proteins. One idea for our research on SynDIG and Alzheimer's disease is that we are going to try both, at least first in mice. We’re going to try to reprogram the mice so that they express higher amounts of this molecule as they get older, and see if that protects against the cognitive decline. And if that’s the case, I think from a feasibility point of view rather than trying to think “Oh, okay, then, can we overexpress this molecule in people?” I think what we would then do is perhaps try to screen a small molecule library that can boost the activity of SynDIG protein that exists in the brain. That might be the more traditional way to go. But again, we could also envision trying to do a gene editing CRISPR-based approach to turn this gene back on, for example, within our older neurons.

Since a growing amount of neuroscience is working on combining the human brain with computers, how do you think information about synapses will be used in the future?

At UC Davis, and I’m sure at many other institutions, we have a center for neural engineering, and brain computer interfaces is a huge area of research within the center. One approach is to try to understand the patterns of large numbers of synapses. There are now ways that you can look at thousands of synapses at the same time, and to identify patterns within those synaptic activities that say underlie a certain behavior. Then in the human brain computer interfaces, for individuals who are suffering from cognitive decline, maybe you can figure out a way that you can stimulate their neural connections using that same pattern that you’ve isolated from the mouse model.

Given the growing importance of AI, do you think that there is a place for AI in your research? What role do you think AI and machine learning could play in future neuroscience research?

One brand new avenue that we’re pursuing right now is to use AI for detecting synapses. Right now, we rely on computer programs to try to isolate the number of green dots in a cell. That’s by far the rate limiting step in all of our experiments. Can we train a computer to basically recognize those synapses and analyze the data for us? Because of this, I would encourage all of you to pursue experience in programming, R or python.

How do you view the current state of diversity in the neuroscience field, and what steps do you believe are necessary to encourage more underrepresented groups to pursue careers in this area?

My parents are originally from Mexico. They moved to California when they were kids, and I was quite fortunate that they were both able to get into the school system and go to college. One of the things I really enjoy is learning about where people grew up, where their formative years were, what were their traditions a child, and what formed them as an individual. And I’ve learned so much from my own colleagues as well as lab members to appreciate the vast amount of diversity that exists. We really only know our own background and our family and our friends. However, we can learn so much simply from asking “Where did you grow up? And what did you do? What was the holiday tradition that you did as a young person, as a child?” I don’t limit my scientific interactions with, or mentoring of my students to “Oh, how’s the research going?” I try to take the holistic approach to understand the person as a whole in order to understand where they are now.

Looking towards the future, what are some unexplored areas or emerging topics within developmental neurobiology that you find particularly promising or intriguing for further research?

I'm actually at a conference right now and one of the most fascinating talks that I just went to was on sleep. We all sleep, I think almost all organisms sleep. And yet we still have no idea, why? We do know that if we don’t sleep, eventually, we will die. Why does this seem so fundamental? We’re now understanding more about the different types of sleep and how sleep impacts different areas. We now know sleep is important for consolidating memory and clearing out a lot of the synaptic junk that you don’t want to keep. The other area, which is a little more challenging, would be the development of consciousness. Where does this emergent consciousness happen? Is it the types of synapses? Is it the activity? Is it the experiences?

If any, what ethical dilemmas have you been faced with throughout your research experience? How did you come to terms with them and/or how did you solve them?

When I was a PhD student and an undergrad I studied cell lines. I became fascinated then with these neurons and then I realized, “Oh, these are primary cultures”, meaning that I had to isolate tissue from an organism. I had to come to the willingness to be able to say, I’m going to sacrifice animals to do the research. That’s one thing that I constantly think about. It’s highly regulated, so not just anybody can start to do research on animals. Our laboratory is reviewed annually. I have to submit animal use protocols every year, justifying the research, justifying the numbers of animals that we use. But ultimately, that can present a challenge. I have pets, I have dogs, I can’t imagine sacrificing them for a study. But yet in my laboratory we sacrifice rodents all the time and again, we can’t do these experiments necessarily in humans, so rodents would be the only other model. It might come to a point where we have such good models that don’t rely on rodents that maybe someday in the future we won’t need to do that anymore.

What other advice would you give to undergraduates hoping to get involved with research and perhaps go to graduate school?

There’s so many opportunities now, but maybe that's also a problem: maybe that there’s too many. Now you can Google summer research experience and there’s hundreds throughout the country. It might be a little overwhelming in order to try to find the right one. But as an undergraduate student, that’s what’s really critical: finding that research experience. The advice I always give is to take advantage of every opportunity that comes to you, and really try to capitalize on the fact that you’re early in your career. Now is a time where you can go up to any faculty, and basically ask to learn about their research. Some faculty might get a lot of requests, but you can also talk to PhD students who TA for the courses that you take and ask about their research and if they’re interested in taking on a trainee to get research experience. For individuals like myself, finding a paid internship during the summer was critical to get that experience. It might be in a distant state, but it’s a great opportunity. You get to meet new people from different parts of the country and it’s not permanent.

How important do you feel creativity is when conducting research? For example when it comes to designing an experiment or coming up with a research hypothesis or a specific topic.

I’ve heard that scientists and artists have a lot in common because you are creating from scratch. One professor told me that you should have some kind of creative outlook in addition to your science. Painting, music, or something, so that you can continue the artistic creative things that you might be interested in, because that will stimulate your creative artistic ideas in science. It seems counterintuitive, but when you really think about it, it makes sense.

What are the challenges you have been faced with and had to overcome as a woman in science and research?

I think one of the things that I, in retrospect, look back on now is the time it takes. It takes longer, in general, for women to develop their confidence in themselves in their field, and I see this in me. I was initially hesitant to ask questions. I was always questioning “Is this the right approach? Is this right?” Eventually, with enough time, and years of experience, you get that confidence. I tell my trainees, especially my women trainees, “Pretend, pretend now that you have the confidence to ask the question, and then tell yourself ‘I know in the future I will have this confidence, and right now I’m just going to pretend’.” Fake it till you make it.

Have you faced any injustices or discrimination because you are a woman?

More than 50% of students in classes I teach are women. But as you get higher and higher along the ranks, you lose that percentage. At my institution there’s less than 10% female full professors and that’s not unique. Part of the challenge is, of course, childbirth. Women have children and I’m convinced to fix or to address this problem we need to figure out how men can have children. That’s not gonna happen, but that’s what I feel might be a way to solve this issue. Now, that being said, I don’t have children, so I don’t have that experience. It just worked out that way: my husband and I married late so it just wasn’t feasible at my age. But, there’s always going to be that challenge. I think institutions are getting better at recognizing the need for longer maternity leaves or stopping the tenure clock. These sorts of things that make sure that the playing field is evenly matched. I try, again, to advocate for female faculty who do have children, who don’t have the flexibility, like myself, to work at home. You can’t just expect things to be equal if women have 25% of their time devoted to childcare at home. That will continue to be a challenge.

You’ve obviously left a very strong mark in your field. What do you think is the best way to make/implement your mark as a scientist and as a researcher within the community?

Something that tells me I’m doing a good job is when I hear years later from my trainees that get in touch with me to say, “Doctor Diaz, I just wanted to let you know that I’m doing this and how much I enjoyed being in the laboratory during the summer”, or things like that, and how that made an impact on their career, and how they’re now paying it forward by training the next generation of individuals to do such and such. For example, just recently, one of the undergraduate trainees, who was in my lab over ten years ago, sent me an email out of the blue saying, “I was thinking about my training and was realizing the impact that you had during my undergraduate training in order to go to the next step.” And this was an individual who’d taken on a position at Moderna eight years ago. She was at Moderna before they became famous and saved the world. Those are the critical things to tell myself that I’m doing the right thing.

In general, what has been your favorite part so far in conducting research?

Talking with trainees. What do they want to do after their PhD? Do they want to do a postdoc? Do they want to go into industry? Do they want to do science policy? For me, again, it’s the flexibility of designing your own experiments and the discovery process. But a huge part is working with undergraduates, with PhD students in the laboratory, and mentoring students in the research they do, or even as more of a general advisor. All the other things we get to do - go to meetings, network, just talk about science and come up with new ideas - are added perks. But it’s the working with the trainees, specifically undergraduates, because I remember myself being so fascinated by running a gel in the lab for the first time.

What is your dream experiment that you would love to do or see done by someone else in your lifetime?

If we could somehow boost the activity of the molecule we are working on (SynDIG), would that be a preventative measure for the cognitive decline in aging. I think a student asked me once “Okay, sure, what if we identify a compound that activates this molecule we’ve studied, and it boosts activity in aging and in aged animals. What about applying this to young people and seeing if that would enhance learning, memory as an aide?” I’m also having that ethical dilemma: what would keep the population from using that earlier? That would be beyond my control, because it would be something developed presumably by a company based on our research. While I would love for something like that to be developed and have therapeutic value for a population with Alzheimer’s, there’s always going to be that ethical question.