Dr. Nicholas Silva

In celebration of National Hispanic Heritage Month, we honor the lives and work of Hispanic scientists who have made significant contributions to our understanding of health and disease. Their dedication and determination serve as an inspiration to aspiring young scientists.

We sat down with Dr. Nicholas Silva, Postdoctoral Scholar at the University of California, San Francisco (UCSF) Weill Institute for Neurosciences in the laboratory of Dr. Anna Molofsky. As a Mexican American and the first in his family to attend college, Dr. Silva has learned valuable lessons about self-advocacy and finding mentors for your career goals at every stage. He has been involved in supporting underrepresented students in STEM since his undergraduate training and is looking forward to training the next generation of students in his new lab, set to open at San Francisco State University (SFSU) in January 2025.

…there are other people like me, and it's really important to represent all individuals in academia. Just because we all have a PhD doesn’t mean we're all prodigies or come from an academic family. I'm the first in my family to go to college, so it's important to shine a light on all of these different lived experiences.

Dr. Nicholas Silva

Let’s start by learning about you and about your research.

I'm currently a postdoc at UCSF in Anna Molofsky’s lab, where we study how the immune system shapes brain development and what happens when this process goes awry. My project is focused on the functional role of a lysosomal protease within microglia during brain development. Microglia are professional phagocytes and the predominant immune cell in the brain. Specifically, I’m interested in how cathepsin B mediates neuronal digestion during brain development using zebrafish as a research model.

The brain is a fascinating and challenging topic of study. When did you first learn about microglia and what made you want to study them?

I was really fascinated with glia biology as a PhD student when I was studying a cell type known as Müller glia, which are found in the retina. In response to injury, Müller glia can re-enter the cell cycle to produce stem cells for full regeneration in the zebrafish. Following a light-induced lesion to the retina, microglia would always be the first responders to eat the damaged photoreceptors. I'd stain them and think they were so cool! When I was looking for my postdoc, I stumbled across a post by Dr. Anna Molofsky, who I knew was working on astrocytes but wanted to start a zebrafish project looking at microglia and synaptic dynamics. This was a perfect fit due to my interest and experience, so I contacted her and ended up at UCSF for my postdoc.

When you started your research, did you have a specific challenge or question in mind, and what have you learned so far?

The goal of my first research project was to get an idea of the transcriptional signatures of microglia during development and identify a region to study microglia-synaptic interactions. My current project is following up on our single-cell sequencing dataset, which revealed a lysosomal protease (cathepsin B) enriched in microglia that was engulfing neurons. My first question was, “What’s the functional role of this gene, and can we figure out what it is doing to mediate this process?”

My research project has shown that in fish, cathepsin B mediates neuronal digestion, so without it, microglia cannot digest neurons. We see the same phenotype when we knock out this gene in mice, which is great because that definitively shows that it's conserved in higher models such as mammals.

Are there specific similarities between zebrafish and human brains that make them a good research model?

We use zebrafish because they are vertebrates with a backbone, just like humans. Brain architecture is quite conserved between the two species, so zebrafish are a great model to interrogate neurological processes in neuroscience. Additionally, zebrafish are transparent throughout the early stages of development, making it ideal for live imaging. Live imaging can be done on rodent models using a cranial window, which is a very invasive method. Lastly, zebrafish have been used to identify various therapeutic targets in several neurological diseases.

How do you think this research will impact the general public and the wider research community?

The brain is a three-and-a-half-pound ball of mass that is composed of a lot more neurons than we actually need, and those neurons need to be removed during development. This process is mediated by microglia, which clean up neuronal debris in the brain. We don’t have a good grasp on the actual genes that regulate this process; however, it all points to the lysosome, the stomach of microglia. My research will make a significant contribution to the research community through the identification of a conserved lysosomal protease, cathepsin B, that mediates neuronal digestion during development.

Additionally, there's an increase in neurodegenerative diseases in aging populations, and microglia are very active in these disease states. If we can figure out how to modulate the activity of microglia, we can have a positive impact on individuals suffering from neurodegenerative diseases in the future.

Were there any hobbies or interests you had as a kid that helped guide you to where you are today?

When I was a kid, I knew I wanted to do science. But to be honest, I wasn't the most academically astute student, but biology was always something that came easy to me. I think the first biology concept that fascinated me was metamorphosis. We had a backyard pond that was a breeding ground for tadpoles and my playground. The tadpoles looked like little black worms and then started popping out legs and the next thing you know, they were frogs jumping out of the pond. After watching that as a kid, I was so curious about biology and knew I wanted to be a scientist.

You said you weren’t academically astute—but yet here you are with a PhD. Can you expand on that a little?

When I was in elementary school, I was not meeting the math and reading standards and received an individual development plan for students with learning disabilities. I worked with a tutor for both subjects a couple of hours each day from 4th grade to 9th grade. In high school, I went to a college preparatory school and struggled to keep up with my peers. I felt inadequate academically and didn't really see college as a path, although I was interested.

In the past, I would feel weird talking about it, but talking about it has allowed me to realize there are other people like me and it's important to represent all individuals in academia. Just because we all have a PhD doesn’t mean we're all prodigies or come from an academic family. I'm the first in my family to go to college, so it's important to shine a light on these different lived experiences.

You’ve had to draw on internal strength, can you talk a bit about any external help like any mentors that have guided you through this?

One of my early mentors was my 9th grade biology teacher Binnie Hong, who told me I was really good at science and made me think I could actually do it. In community college, I had another mentor who provided me my first research opportunity, which was instrumental in getting into a lab at SFSU. Under the mentorship of Dr. Megumi Fuse at SFSU, I became involved in various programs geared towards marginalized individuals, such as the NIH MARC and the RISE programs, and I had a plethora of additional mentors that helped me prepare for a PhD program. Another great mentor is my PhD advisor, Dr. Peter Hitchcock, who still reads my grants and manuscripts.

Through all this, how did you advocate for yourself in the face of challenges?

I've learned from being in academia that you really need to be your biggest advocate and find mentors who will support you. Oftentimes this is not the mentor that you primarily work with. We traditionally think we need one mentor, but really you need multiple mentors at different stages of your career. What's helped me persevere is my community of colleagues and family who support me, and they don't necessarily have to come from the same background.

What would you say is a good way for students to find mentors?

I always say to try to find the individual that you would like to learn from and who has the teaching style that best fits you. So, for example, if you really want to learn how to do a certain technique, do your research to figure out who does it and ask people about their mentoring style and if they are available. If the answer is yes, then contact them. I think it's important to be proactive about your career and beyond.

How has this journey impacted how you support students, particularly Hispanic students, in your research and teaching?

Throughout my career, I've had the privilege of mentoring several students from marginalized groups, including LatinX trainees. Since I was an undergrad trainee, I've been part of SACNAS, which is a national group of chapters geared towards mentorship for Native American and Latinx individuals. SACNAS and the Annual Biomedical Research Conference for Minoritized Scientists (ABRCMS) were my first scientific research conferences. Thus, it’s very important to me to attend when possible and continue to be part of this community.

And since your undergrad or even graduate school, what improvements have you seen in STEM for Hispanic researchers? Are there still areas of further improvement?

Based on my own experience at the University of Michigan, where I was really involved with the program and recruitment, enrollment of Hispanic individuals has really gone up since my time as a graduate student there. When I started, there were a total of eight in our cohort, and three of us were Latinx. Recently, the cohort had about 20 people, and I would say eight of them identified as Latinx.

So, it's a huge improvement, but I think something that needs to be addressed and improved on is retention—and this is across marginalized groups. Once they are admitted, the completion rates don't match the admission rates. This is what people would refer to as the leaky pipe. Trying to figure out ways that we can support these individuals to completion of their PhD is important.

Is there anything about Hispanic culture you think most people are unaware of that you would like them to know?

We're similar to other cultures with core values of family, love, and food. I've been exposed to multiple cultures throughout my academic career, and I noticed we often share more similarities than differences. If we can learn that from one another the world would be a much better place.

I’m sure you will try to help with improving diversity efforts when you start your own lab. Where would you like to take your research and what culture would you like to establish in your lab?

In terms of where I would like to take my research, I'm still very much interested in glia biology. Not only during development but also in states of hyperexcitability and seizures. I envision my lab in the next decade or so trying to address some questions specific to how microglia might be mediating states of neuronal activity after seizures.

In terms of lab culture, I've also been thinking a lot about this and what I want my lab to value and represent. I want to create a welcoming environment that's equitable for all and provide opportunities for trainees lacking support and resources. So, I envision a lab that is quite diverse and not just filled with Latinx students but students from all races, ethnicities, and backgrounds.

Something that's also super important for lab culture is being respectful to other individuals in the lab, but also to enjoy what you're doing. Science is very difficult so having a support system is super important. Morale, culture, and respect are going to be core values of what I'm trying to cultivate for my lab environment.

I know your Hispanic heritage is a huge reason why you love to support underrepresented student populations. Can you tell me what aspects of your Hispanic heritage do you most enjoy and like to share?

I'm a second-generation Mexican, and both of my grandpas were born in Mexico. Some of the best things from our culture are the food and love around family. My dad's father owned a carnicería, which is a meat market, and a panadería, which is a bakery. My dad would pick me and my siblings up from school, and we would go to the market until he got off work. All my aunts and uncles worked there, and it was so special how food and the market brought my family together. I have great memories of running around and playing with masa, dried corn, and beans with my hands, and my aunt saying, “Don't do that, customers are going to buy this stuff.” 

Are there family recipes that you still make?

One of my go-to dishes is pozole, similar to menudo without the tripe or the lining of the stomach. It’s made with pork and hominy, which is little corn that has been soaked in water, so it's quite soft, and it has a red base chili broth. Sopa de fideo is also really great! It’s basically macaroni shells with tomato sauce, onion, and a little bit of cheese. I still make both dishes quite often.  

Are there any fun traditions you’d like to start in your lab?

I definitely want to make sure everyone feels represented, so I want to ask them, “What holiday or event do you want to celebrate?” And have something like a potluck around their culture and food, or if they want to suggest a movie night or something like that, I think that would be really cool. I also want to celebrate milestones, whether it's a grant or publication. Whatever it is, I think it's important to acknowledge that, whether we pop a bottle of champagne or take everyone out for lunch or grab an ice cream.

You’ve chosen to stay in academia and start your own lab rather than take an industry position. I’m sure mentoring the next generation played a big role in that decision. But aside from that, what is the most rewarding aspect of participating in academic research?

For me personally, the excitement of discovery has not diminished. I feel like a little kid when something works. When you have a hypothesis and it's actually correct, that is the biggest high for me. I get so excited going into the lab and seeing if that experiment worked.

And, of course, working with trainees and my colleagues is one of the highlights of my career. I've met some amazing people along my career path. You never know what you’ll learn from them, and there's so much growth that can come from that.