“I’ve always wanted to work to shorten the gap between discovery and actual use in patients.”
Oscar Vazquez, Neuroscience PhD Program alum (entering class of 2010)
When Oscar Vazquez was serving as a US Marine in Iraq, he witnessed firsthand the devastating effects of traumatic brain injuries, and became determined to find new ways to improve the lives of patients. After earning a PhD in Neuroscience at UC Berkeley, he began medical school at UC Davis, where he is currently a fourth year student. At the time of this interview, Vazquez was finishing a sub-internship in neurosurgery at Stanford University.
Vazquez grew up in Puerto Rico and initially wanted to become a veterinarian. He joined the Reserves after high school, intending to serve in the military while earning his degree at the University of Puerto Rico. After 9/11, he was sent into combat and ended up serving eight years in the Marine Corps. Vazquez’s experiences in Iraq affected him profoundly, and he decided to dedicate his career to developing better treatments for traumatic brain injury (TBI). He then returned to college and completed his BS degree in Biology. Because the University of Puerto Rico did not have a neuroscience program, he sought out opportunities elsewhere, and began doing neuroscience research at Stanford through the Amgen Scholars Program.
Vazquez joined the Berkeley Neuroscience PhD Program to work with Daniela Kaufer, who is a military veteran herself, and studies mechanisms of brain plasticity in response to stress and neurological insults. Vazquez’s thesis was focused on the molecular mechanisms of post-traumatic epilepsy and potential ways to prevent it from occurring.
Inspired by his experiences learning from and collaborating with clinicians as a PhD student at Berkeley, Vazquez decided to go on to earn an MD so that he could work directly with patients and launch his own clinical trials. Not content to accept a lack of effective treatments when patients are in need, Vazquez also co-founded a cancer immunotherapy company. He has a particular interest in developing new treatments for conditions that he feels have not gotten sufficient scientific attention, such as TBI and diseases that predominantly affect women.
Read the following Q&A with Vazquez to learn more about his unique career path, research on brain trauma, and how his experiences at Berkeley inspired him to take action to create real-world solutions for pressing medical problems. This Q&A has been edited for brevity and clarity.
Rachel Henderson: How did you become interested in science?
Oscar Vazquez: My father was a biologist working at a zoo. What that meant for me and my sisters was that we had the chance to literally go to the zoo every day. So we kind of grew up in the zoo, and early on I picked up on the passion of working with animals and volunteering at the zoo. Doing that volunteering and getting the chance to work with a veterinarian at the zoo got me excited about understanding how diseases take advantage of the regular biology to actually survive and spread and stay as an active member of the ecosystem.
That made me think, early on, that I was probably going to follow that pathway of becoming a biologist and then becoming a veterinarian, because I liked the opportunity to help animals and I thought that was the most exciting job that you could possibly get. So that’s where it started for me. I [volunteered at the zoo] since I was about 10 years old, all the way up until I was graduating from high school.
When I was graduating from high school, I had also made it one of my goals to serve in the military. That came from growing up in a family with a long military history. What I thought at the time would be the best way to combine those two goals — becoming a biologist interested in the biology of disease and serving in the military — was that I was going to do service with the Reserves while going to college. I thought that this will give me, later on, the opportunity to get a commission as an officer in the military, and then continue to define what I want to do — either continue to have a long-term military career or just leave the military once my service was completed so that I could concentrate on becoming a veterinarian.
This was the military before 9/11, which was a very different culture, a very different time than what it eventually became after the terrorist attacks on 9/11. When that happened, the seriousness of my job within the Marines became more active and more serious. Eventually, in 2003, I was asked with the rest of my unit to leave Puerto Rico as a big contingent to join a bigger force that was being assembled in California to go into Iraq. When that happened I was about halfway through my undergraduate training as a biologist.
In preparation to make that military operation, I started getting more and more experiences in military trauma and the kind of injuries that you could expect from a military conflict, and that was very interesting to me. It was a whole different type of biology of disease than what I had been exposed to before. But then I had the unfortunate experience of actually witnessing what those injuries actually meant to a lot of servicemen and women. I deployed to Iraq in 2004, and one of my colleagues suffered a traumatic brain injury. What’s particularly unique about that type of injury is that it is different from those other injuries that I had trained for, as far as traumatic injuries from combat. We really didn’t have options that would promise a full recovery from their injuries, or that even the recovery that we could get would be sufficient to keep our servicemen and women in the service.
One thing that kept happening, back in the day, was that people who had traumatic brain injuries would develop very debilitating sequelae from that type of injury and ended up having to leave the service altogether. Which, for a lot of these individuals, was a very devastating outcome because a lot of them had chosen a career in the military and that kind of defined who they were as individuals. That’s what they had concentrated most of their youth, most of their energy, and most of their productive years in life [on]. Then all of a sudden, because of his injury, which is kind of invisible in a sense because a lot of them would recover well from the actual superficial trauma … they would have to change their entire life. Not only them but their families as well, because of all the problems that can come with TBI.
So that was very life changing for me because … there seemed to be so many unanswered questions. What I thought at the time, was that the attitude in the service and even within the medical community was, ‘There’s just nothing we can do. Our hands are tied.’ I wanted to do something more than just sit and say that there’s nothing we can do for these kinds of injuries. So that led me to want to look for ways that I could continue my studies, but focus more on this one problem.
My contract [in the Marines] was about to be completed, and I was facing a decision whether I wanted to reenlist and continue this career in the military that I had built, because I ended up serving eight years in the Marines, or whether I wanted to take this somewhere else. I took the leap of saying that I was going to leave the military and go back to college, with the intention of finishing my degree in biology.
Back to college
Originally, I left the Marine Corps with the idea that I was going to go to medical school to become one of the providers, one of the people that I saw while I was in the military that were actively involved in the care of these patients. Because I figured that if I want to help these guys, that’s what I needed to do. That changed, because when I went back to Puerto Rico to finish my degree, I got involved in doing research at the bench. Not only did I really enjoy that part, I also had a chance to learn, through working with the different mentors that I had, that one of the reasons why we did not have a lot of therapeutic options for patients with TBI was because the work was unfinished when it came to researching the process, the best approaches of care.
It was the kind of injury that we had not seen a whole lot, or at least not in a dramatic way until the conflict started again. We had done a lot of research on [TBI] during previous military conflicts, but not so much afterwards. One of the things these mentors kind of let me figure out by myself was that if I really wanted to have the biggest impact that I could on this patient population, the best way to do so was to actually commit to do the work on the bench. To join the groups that were working on some form of initiative concentrated on knowing more about the type of injury, knowing more about what are the best ways to have an effect when it comes to therapeutic choices and options.
As an undergraduate student in Puerto Rico, I started looking for opportunities to learn more about how nervous tissues respond to injuries. We did not have a neuroscience program [at the University of Puerto Rico] at the time. I was a biology student, interested in neuroscience, but [did not really have] a lot of opportunities to do research in neuroscience. As an undergrad, my research was actually on engineering magnetic nanoparticles that we were building for the purpose of delivering chemotherapy to cancer cells and tumors.
But during the summers, I really took that as an opportunity to find places where I could go do the research that I was actually excited about, which is how I came to learn about Stanford [Ed. note: where he did research for two summers through the Amgen Scholars Program] and all the research initiatives that existed in the Bay Area. One of the projects that I got involved with [at Stanford] back in 2009 was an initiative led by Dr. Douglas Vollrath who was studying how retinal degeneration manifests itself in several models. The idea was that by studying how neurodegeneration presents itself in this very accessible model, the retina, … we could actually learn more about how degeneration of nervous tissue happens in the brain and all the components of the central nervous system.
Then the time came for me to apply for graduate programs, and I had the lucky opportunity of meeting with Daniela Kaufer. Daniela Kaufer has this very cool initiative that really aligned perfectly with what I wanted to do. Because not only was she interested in the neurobiology of disease of several conditions, but she was also a military veteran who was working with another military veteran for the purpose of discovering the molecular underpinnings of post-traumatic epilepsy. Why was it that after the brain was exposed to the mechanical trauma that came from a TBI, that the brain would also change the way that it behaves as far as firing patterns?
I realized that was like the planets aligning for me when I was on the interview trail at the time. Because it’s the place where I wanted to be, the Bay Area; the ecosystem of research that I was really interested in being part of; the kind of project that I wanted to focus on; the kind of question that I wanted to answer; and to the benefit of the patient population that I wanted to serve. So that’s how I ended up joining the Helen Wills Neuroscience Institute, and started working with Daniela on trying to figure out a way to approach the very complex question of how seizures would develop after TBIs, and how can we actually do something to intervene therapeutically to promise better outcomes for patients.
RH: What was your thesis project about?
OV: When I joined the Kaufer lab, Daniela explained to me that they had [made] some interesting observations that stem cells within the brain had the ability to respond to some of the signals that were initiated after traumatic brain injury, and that there was a possibility for a role of stem cells in the onset of epilepsy. So that got me curious, because it involved work on traumatic brain injuries, but [I was also interested in] the regenerative capability of the brain.
When I came in, my project was to characterize the interaction [between] stem cells and the different molecular stimuli that came after a TBI. We had an interest in working with serum albumin [Ed. note: a protein in the blood normally excluded from the brain by the blood-brain barrier]. One of the things that Daniela had discovered before I joined the lab was that serum albumin by itself was sufficient to elicit spontaneous seizures in animal models.
So I characterized how serum albumin has the ability to do this. One of the postdocs in the lab, [Lydia Wood], had taken on that project a couple of months before I joined the lab. One of the things that we knew could explain a hyperactive state … would be if this circuit would actually increase the amount of connections that neurons made with each other. So she [wanted to know] — do we see increases in synaptogenesis when animals are exposed to serum albumin?
I helped [Wood] characterize that. We saw that animals exposed to serum albumin had the response of increasing the amount of synapses. And we found that it was very specifically associated with TGF-beta signaling, which was the other part of that puzzle. Before I joined [the lab they] showed that albumin, when exposed to brains, had the ability to bind to TGF-beta receptors and activate TGF-beta signaling. … [We found that] albumin is exploiting this signaling pathway to change the way that cells within the network are responding. The cells that actually were the most involved in that process were astrocytes, not stem cells. It looked like it was the signaling within astrocytes that led to the changes in circuitry that allowed for seizures … So albumin was able to make neurons more likely to fire.
That may explain why we see an immediate change in the way that neurons fire, but … epilepsy is a lifelong disease that requires the observation of multiple seizures. So I designed the hypothesis that there’s got to be a role for stem cells, there’s got to be a role for changes within the circuitry that make it more likely that from the moment that trauma occurs and this exposure to serum albumin takes place, something more durable must change in the network to allow for seizures to continue to happen throughout life.
I designed this model in which not only were we exposing animals to serum albumin, but [it was] more like what would happen during a traumatic brain injury in which you break down the blood-brain barrier and it remains open for a couple of days until it has the ability to heal. … So for at least seven days, the animals were being exposed to [continuous] regulated flow of albumin, mimicking the opening and eventual closing of the blood-brain barrier as it would happen after a traumatic brain injury. After the animals were exposed to those conditions, I looked at what was happening with the stem cells [particularly in the hippocampus], the astrocytes, and all the key players of that network.
What I found is that when animals were exposed to serum albumin and this activation of TGF-beta signaling occurs, there was actually an increase in the number of new neurons that were added to the network. … It wasn’t only that the stem cells were proliferating, but that they were making, particularly, neurons. … Which you might think is a good thing, but in this case, the way that [these new neurons] were connecting with each other was very different than what you normally would see. They were abnormal type neurons that were making connections in a way that was not seen in this model before, and that happened to mimic a lot of what was characterized in other models of epilepsy in which neurons that are born in the hippocampus of an animal that has undergone seizures tend to develop these recurrent networks. They start connecting with parts of the hippocampus that will make it very likely for them to trap, basically, electrical impulses within the circuitry of the hippocampus, and then by doing so, create a recurrent network that is part of an epileptogenic brain.
So immediately the question became, if this happens through this mechanism, it stands to reason that we can probably do something to prevent this from happening. We looked at using several types of TGF-beta receptor inhibitors. I [found] that yes, we can inhibit that process. More promising to me, at the time, was that we could inhibit it with a molecule that had already been FDA-approved for use in other conditions. In this case, I took Losartan, which is an angiotensin receptor inhibitor that we had known for some time may have some potential to be used in these kinds of patients. Even though it’s supposed to be an angiotensin receptor inhibitor, it had shown the ability in other models of disease, particularly diseases of the gut, to inhibit TGF-beta signaling. We hypothesized that maybe [if we] put it in the brain, we might be able to inhibit the signal and therefore prevent the changes that we’ve seen are associated with this epileptogenic process. We did that, and found that was the case — we were able to prevent these architecture changes in the hippocampus of the brain of these animals.
RH: Beyond the research, what was your experience in the Neuroscience PhD program like?
OV: I had a really, really good time getting to know about how broad neuroscience is, which I think was the great part about it. Having come as a molecular biologist, and then doing molecular biology during the program, I appreciated that the program [made] sure that I got the exposure needed to become a participant in the neuroscientific conversation by getting involved in other aspects. For example, our qualifying exams were made in a way that you had to take outside projects. If you were a molecular biologist interested in neurobiology, you couldn’t just stay within the boundaries of molecular biology. You had to go out there and learn a little bit about all the other types of disciplines within neuroscience. You had to not only go and learn it, but also present it to the community and show them that you have mastered some understanding of all of these components of what neuroscience actually is.
That was a phenomenal opportunity, which didn’t come by design because when I chose to come to Berkeley, I was enamored with the idea of working on this project, working with Daniela. But what I actually realized is that you do need that. If you’re going to eventually go and become a full-fledged neuroscientist, you’ve got to be able to understand what we are learning from all of these other disciplines within the field.
And now, as a clinician, to understand what the imaging studies are telling us about the way that the brain connects, and all those things, are very important to me. I sincerely appreciate having had that opportunity at Berkeley because of the breadth of scientists that we have in our community. But also, how much we push our students to go and try them all, to actually do part of the science in every single one of these other disciplines, [and to] take the courses. We went to the retreats and we got to be participants in the conversation … and the program gave us the opportunity to do that. Not only in a professional setting, but also keeping us together as a cohort. That was great because I had a chance, until very late in my time as a grad student, to still interact with all my peers in my cohort. They were doing their own things, their own projects — all sorts, like computational neuroscience and cortical recordings with actual patients. We were helped by the program to stay together, to work on things together, and to talk about our challenges together. That was nice, I really enjoyed that as well.
RH: Why did you go to medical school after earning your PhD?
OV: The summer after my third year [in graduate school], I realized that I really liked what I was doing, I really liked where the project was going, but there were a couple of things that were missing. There was a component of distance from my sources of motivation that had changed, greatly, since I left the Marines. I thought that I was working too far away from the reasons why I chose to go into this path, and that I really needed to still have that patient contact. That was one thing that was very important to me, to remain connected to the people for [whom] I was doing the work.
I felt that if I was to continue on the path of just doing research from the bench, that distance may grow farther and farther. That’s one thing that I actually ended up noticing while working with different teams; [which is] one of the good things at a place like Berkeley, because the opportunity to work in collaborative environments really gives us the chance to grow as more mature scientists. If I was somewhere else where the program would’ve given me a very narrow range of movement … I think that I would have probably missed that.
Even before my qualifying exam, I had the opportunity to collaborate with faculty from the department of mechanical engineering, because I had an engineering background and I wanted to see whether there was something that I could bring from that into my work. I [also] collaborated with faculty from Israel, Stanford, and UC Davis. I saw how different teams work, and there were teams that I was collaborating with that really worked hand-in-hand with the patient community.
For example, Mike Rogawski at UC Davis was involved in my project because he was one of the developers of antiepileptic drugs. He had a lot of interest in wanting to help us design the next generation of antiepileptic drugs for this particular patient population. But he was a neurologist. He had his animal models, where he was doing a lot of experiments, but he also put all the compounds he was developing into his own patients to run his own clinical trials. That was exciting to me. I said, ‘Oh look, this is a way that I can do that.’ Later on, I had a chance to meet another clinician [Allyson Alexander], who, as part of her residency program as a neurosurgeon at Stanford, was doing the animal work that I was doing. I was doing the neurosurgery for her animals and she was taking them and doing the electrophysiology. So I saw another way in which you can work with a patient population, even within neurosurgery, and still do your experiments.
Then, at Helen Wills, Bob Knight was teaching a course called clinical neuroscience, in which he partnered with Mark D’Esposito, who is a neurologist by training. Mark was working at the VA and took the students to do rounds with him. You get to see how he, in that very special position as a clinician, can have that patient connection that I found to be very rewarding and energizing. And I thought, I’m doing this for the rest of my life. This a lifelong commitment that I’m making, so I better position myself at a place where I feel that every morning when I go out to do my work, whether it’s at the bench or at the bedside, I am excited and 100% committed to what I’m doing.
That’s when the idea came. If these components are important to me, to be able to go and meet the patients that are benefiting from all the hard work that we’re doing at the bench, then what are a couple of years more in training? It doesn’t matter. I have already committed to being a lifelong learner. Let’s just add the chance to work with patients directly as well, because that will be a necessary component to take [my] research forward. I [won’t] have to wait until someone else picks up the clinical trial, or somebody knocks on my door and asks, ‘Hey, do you want to do a trial with me?’ I can actually put the trial together myself.
So that’s where the idea came from for me to go into medicine. In particular it was [when] Allyson Alexander … took me for the first time to the operating room to see what a neurosurgeon does. It was life changing. I started to imagine how much satisfaction I could draw from doing that. I knew that I liked doing procedures, working with my hands, and making tools and developing solutions that actually were usable in the operating room. I knew that was exciting to me, and then I saw her do it. I knew at that moment, this is what I want to do for the rest of my life.
On starting a company
I began a collaboration with a faculty member here [Jose Torres], and we have started a company [called Cancermune]. That is another one of those things that go into your DNA when you become a student at Berkeley — there’s a strong culture of entrepreneurship; and to always work to shorten the gap, to make things more efficient. When you see the opportunity for something to work for a particular group, in this case patients, do not wait until things get developed. Do not wait for somebody else to pick it up from you. You’re a scientist, but you are also a leader. That was one of the things that came from going to Berkeley. There’s this notion that you have to take the initiative, you have to go out there and make changes. Because if you don’t do it, no one will, and things would just end up sitting in a pile of papers for the rest of history. That influenced me in the sense that since I’ve left Berkeley, I’ve always wanted to work to shorten the gap between discovery and actual use in patients.
While I was taking my immunology course [in medical school], I had a chance to meet and develop a nice relationship with [Torres] who was in charge of the immunology course. Then when I was doing my clerkship in OB/GYN, I found out that there were all these diseases we have neglected for a long time. When I say we, I mean the clinical community at large, but also society allows these neglected diseases in women’s health, and we have no reason for them to be neglected. And that created the unfortunate situation where there are conditions that afflict women on a very regular basis, that are very debilitating and disabling, and there is nothing we can do.
At the time, I was interested in things like endometriosis and HPV and cervical cancer. I started doing my own research on what we are doing from the bioinformatic aspect and from the engineering aspect of vaccine development for HPV. I stumbled upon some data that was interesting, that I thought just needed to be pushed to market as soon as possible. I connected with [Torres] and asked him, ‘Why haven’t we done this?’ and he said, ‘Because no one has actually taken the initiative to make it happen.’ I said, ‘Well, do you want to make happen with me?’
We started with this interest in developing a new generation of vaccine for HPV. Right now we’re [developing] immunotherapies for the treatment of malignancies. In particular, we’ve taken an interest in glioblastoma and breast cancer, and we have developed some therapeutics that we want to take to human trials. Before we take it to human trials, we are [taking it to] trials with companion animals. One of the unique things that comes from having gone to medical school here at Davis is that by having the veterinary school, it makes a lot of resources for animal research very accessible. One of the ways that we have thought about shortening the gap between development of a therapy and access to patients is by using multiple animal models at same time, but also models that are better at mimicking the disease. The good thing with companion animals is they have a lot of the things that you would actually find in human pathologies. … So we are recruiting animals that have the types of injuries that we’re after, and hoping that pretty soon we’ll put in the pipeline some therapies that we’ll be able to use in human trials.
You really never know where your path is going to take you. I think this is where having gone to Berkeley really helped me. Because you never know where you’re going to be, but when you find yourself in a situation where you could solve a problem, you need to be able to recognize — oh, this is a problem that I can solve. Not only that, but I can actually follow through and see it become an actual solution.