Researcher Spotlight: Dr. Antonia Dominguez

“Our ability to make progress in ALS depends so much on attracting the best young scientists into the field. The ALS Association’s Milton Safenowitz Postdoctoral Fellowship program is a critical part of that effort. Almost 90 percent of our fellows stay in ALS research, making up a significant fraction of the younger generation of ALS researchers.” – Dr. Lucie Bruijn, Ph.D., M.B.A., Chief Scientist, The ALS Association.

Meet Dr. Antonia Dominguez, an ALS researcher who was recently awarded The ALS Association’s Milton Safenowitz Postdoctoral Fellowship! Read about what drew Dr. Dominguez to the field of ALS research, her passion for her work and how the support of people like you is critical to advance important ALS research.

What has the support from The ALS Association meant to you?
The support meant a lot to me. When I the received the award email, I was ecstatic and extremely honored! Many people apply and not many get it so I was very excited that The ALS Association saw the potential in my work, especially because our lab is fairly new to the ALS field.

Do you have a message for the donors who helped make your project possible? As you know, Phi Delta Theta Fraternity contributed to your fellowship.
I was recently featured in a Phi Delta Theta newsletter and I was happy to learn how they raise money through athletic events run by their members. My whole life I have been involved in some sort of athletics – volleyball, running, playing basketball - so it is awesome to see the link between how they raise money for The ALS Association which helps support my fellowship and is tied to their athletic goals. I was excited and honored to receive their support!

“There’s nothing more gratifying to our Iron Phi participants than contributing grants to those who are enthusiastically conducting ALS research. Phi Delta Theta’s roots are at college campuses across North America so supporting a campus-based researcher is important to us. There are 150,000+ Phi Delts across the world cheering on Antonia as she conducts her research!” – Steve Good, Senior Director of Engagement, Phi Delta Theta Fraternity

Do you think the ALS Ice Bucket Challenge has inspired more scientists to investigate ALS?
Yes, I definitely do. While it was happening, everywhere you looked you would see the ALS Ice Bucket Challenge. It brought ALS awareness into the public eye and with it came funding for The ALS Association. As for ALS research, because many scientific fields are interwoven and overlap with each other, the increased funding and awareness resulting from the ALS Ice Bucket Challenge has drawn researchers from many areas to contribute effort towards ALS, as new support opportunities arose. I am grateful for that because my work is benefiting directly from donations to the challenge.

How can we attract more dedicated researchers such as yourself to pursue ALS research?
Having fellowships like The ALS Association has for postdocs is a wonderful idea! It is a great opportunity that helped me figure out how to apply the tools I am currently working on to address a medical condition like ALS. Another idea is to setup unique research opportunities in undergraduate institutions to spark interest in science and to pursue research at an early age. My research experiences as an undergraduate at New Mexico State University and summer internships at Harvard Medical School sparked my interest in research. One summer at Harvard, I studied genetics and that experience is why I wound up pursuing genetics in graduate school.

Speaking of that, what is your academic background and how did you get involved in ALS research?
I grew up in Grants, New Mexico, a small mining town about an hour outside of Albuquerque. For undergrad, I attended New Mexico State University and majored in biochemistry. There I started my research career early on, working alongside my older sister for four years, who was a graduate student in a plant biochemistry lab. It was a unique experience because I had no introduction to research previously but liked science. It exposed me to the ins and outs of what it meant to be a researcher. I was part of a research program at NMSU that supported research opportunities for minority students, so I was paid to conduct research. I am lucky that conducting research has been my main job since I was 19.

Next, I went to Stanford for my Ph.D. in Genetics in Dr. Renee Reijo Pera’s laboratory where I studied genetics in relation to fertility. A lot of my work used induced pluripotent stem cell (iPSC) technology, which had just come out when I started graduate school. For my postdoctoral work, I joined Dr. Stanley Qi’s Lab at the University of California San Francisco (UCSF) when he was a synthetic biology fellow and moved his lab to Stanford three months into my postdoc. Now my work is based on developing enhanced CRISPR/Cas9 based tools used for activating and repressing disease related genes.

What do you like most about the ALS field of study?
I appreciate the amount of work that has gone into establishing the genetic causes of ALS, like the C9orf72 repeat that I am studying. This solid foundation allows us to use our tools to address important questions. It is unique to come into a field where so much work has gone on in a short amount of time and to see how we can push the ALS field forward by applying completely new and different techniques.

What challenges you the most?
Knowing the right questions to ask, especially since I am new to the field. But it is beneficial in a way, because I have to constantly read literature and figure out the best ways to use my specialty to study ALS. It is exciting to learn something new, having the support to do my best work and to hopefully make a big impact!

What qualities make for a good scientist?
My husband is also a researcher, so we sat down and came up with this list together. You have to have a huge amount of curiosity to be willing to put in the time and effort that it takes to do research. Patience and perseverance are important, especially when things do not work as you initially expected - being open minded and adapting your approach when needed. Integrity: to be able to be honest and moral about the work you do and the results it yields. Collaborative: scientists these days are extremely collaborative, because the best work often occurs when technologies and ideas come together from across disciplines. No one individual lab has all the tools and knowledge needed to ask the best questions possible.

What are you most passionate about in research?
The thing that keeps me going is that I love my work using human iPSCs. I can see their potential in disease modeling and regenerative medicine. I took my experience with iPSCs in graduate school and now I can combine genome engineering tools to iPSC biology to ask unique questions that are important for ALS that will hopefully lead to potential therapies and maybe even a cure.

What do you like least about research?
Sometimes not everything works as expected and I can get bogged down in the details and can lose sight of the big picture of why I am doing what I am doing. But it is nice to do an interview like this or to talk to someone outside of science. That really gets me back to why I am doing the work I am doing. My mind always goes back to the people I am working to help – people living with ALS and their caregivers.

Is there a mentor that stands out to you? Tell me how he/she helped you.
The person that stands out to me the most is my sister. There are no other scientists in my large family and I am the youngest of forty cousins. The fact that my sister is a scientist and runs her own lab in breast cancer research at the University of New Mexico is amazing. I have always looked up to her. She is the first person to get me into research. She helped me with all graduate school applications and read every single fellowship I ever submitted, including the Milton Safenowitz Fellowship. It is a unique experience to have someone you are so close with as a mentor who has same exact background as you. To have her to help with my own research and to see her succeed has meant a lot. To this day she still helps me and now I can help her. It is a give and take mentorship.

In layman’s terms, please give me some highlights of your project funded by The ALS Association’s Milton Safenowitz Postdoctoral Fellowship for ALS Research.
I am developing tools that act like a light dimmer for gene expression. We have the ability to target a specific gene and turn the gene’s levels of expression up or down, which is a relatively new capability. Then we ask the questions: What happens when you use this dimmer to turn an important ALS gene up or down? Motor neurons are a type of cell that dies in ALS – what happens to the survival of motor neurons in a person living with ALS vs. those from a healthy person? The basis of our work and the ALS project is focusing on and tuning the levels of the C9orf72 gene, the most common genetic mutation in ALS. Also, C9orf72 is known to sequester important RNA binding proteins, which are linked to motor neuron toxicity. We are also interested in targeting these RNA binding proteins, tuning their levels and seeing what happens to motor neuron survival.

In your studies, you use a new technology called CRISPR/Cas9. Can you explain CRISPR/Cas9 technology and why it is so important to your project and ALS research?
The basic biology behind CRISPR/Cas9 is quite fascinating. It is actually a bacterial immune system that bacteria use to fight off invading viruses. It works by targeting a specific DNA sequence and the Cas9 protein makes a break in the DNA. This DNA targeting was harnessed by researchers to make specific edits to cells’ DNA. Previously, this editing was difficult to carry out, but now it is quite simple and many labs are using the CRISPR/Cas9 system to target just about any gene in many types of organisms. What is unique about our lab is that my advisor, Dr. Stanley Qi, broke the CRISPR/Cas9 tool. This is important because he took the Cas9 protein that causes the double strand break in DNA and took away its ability to cut DNA. We can still target a specific DNA sequence but instead of cutting, CRISPR/dCas9 (deactivated Cas9) can bring in different effectors, meaning a protein that activates gene expression or represses gene expression. Now, CRISPR/dCas9 acts like a shuttle to get an effector to a specific gene target in order to tune its expression levels rather than cutting the DNA. So breaking CRISPR Cas9 was very important. I tell people that “Dr. Qi broke CRISPR/Cas9, but it is a good thing.” With this CRISPR/dCas9 system, we really try to think outside the box to make the system better or use the system to do something new.

I read that you are collaborating with Dr. Steven Finkbeiner, a member of our Neuro Collaborative program. Can you talk briefly about your collaboration with Dr. Finkbeiner in regards to your project?
In the first month of my postdoc, we met with Dr. Finkbeiner to discuss how we could use the tools in our lab to answer important questions in neurodegenerative diseases such as ALS. The C9orf72 gene came up, and we started to research the repeat and what it meant for motor neuron survival. This meeting spurred collaboration between our two labs and helped shape the topic of my Milton Safenowitz Fellowship. Dr. Finkbeiner’s lab has the unique ability to image motor neurons over time to address their health and how long they can survive. The question we want to ask is: What happens to motor neuron survival when we change the levels of ALS genes like C9orf72 with CRISPR/dCas9? They have expertise in producing motor neurons derived from induced pluripotent cells (iPSCs) from people living with ALS. Once we have the tools up and running to change the levels of ALS genes, we will work closely with them to monitor the effects. Our collaboration is valuable because Dr. Finkbeiner and his lab members have a ton of experience in this field.

What else do you think is exciting in ALS research? What are the bright spots on the horizon?
I think we are in a really exceptional spot for sequencing technology to read DNA – it has become much cheaper and also more powerful. And not only can CRISPR/dCas9 rewrite the genome by editing it, but it can also regulate it. Pairing genome sequencing with genome engineering tools like CRISPR/dCas9 could lead to potential therapies, new drug targets or a potential cure.

What is the potential impact of your project on ALS research?
A lot of researchers are editing genes for potential therapeutic purposes. What we are trying to think about is that maybe the gene does not need to be edited, but instead maybe the gene levels need to be changed back to normal. We want to tune the levels of genes that are mis-regulated in ALS to potentially have motor neurons survive longer. This is an exciting but difficult task. Our experiments could form a basis of ALS gene regulation and lead us down a path to a potential therapeutic tool for ALS and rescue motor neuron survival. This would be amazing!

What do you do for fun?
I enjoy playing sand volleyball. I played indoor in high school and then sand volleyball for fun in college, and I still play now. We have a great community of players and I even met my husband on the sand! I also enjoy rock climbing and hiking or anything outdoors.

Who are your heroes in real life?
My parents and my sister, who I have mentioned many times during this interview. My parents do not have science backgrounds but have two daughters in research. My parents’ influence and support has meant so much to me.

Do you have any hidden talents and is there a talent you would like to have?
I am the resident photographer in my lab. Almost all of the pictures on the lab website have come from me. I enjoy photography and am constantly trying to improve my skills. I would like to learn how to play a musical instrument and play with my nephews that are excellent violin and piano players.

What is your idea of perfect happiness?
Going home and being surrounded by friends and family. It makes my day even better!

What are your aspirations for the future?
I always had the idea that I wanted to run my own research group. It is an extremely difficult road to travel to get a position like that. I understand this, but am enjoying my postdoc and working hard to produce the kind of work that would allow me to start my own lab.

Are there last thoughts you would like to share?
Our lab is in a very unique place to take big steps in new directions. Although there will be much to overcome along the way, we are excited that we bring new technologies and new ideas that can help people living with ALS and to build a foundation for important therapies.


About the Milton Safenowitz Postdoctoral Fellowships:

Founded by the Safenowitz family through The ALS Association Greater New York Chapter in memory of Mr. Safenowitz, who died of ALS in 1998, Milton Safenowitz Postdoctoral Fellowships are to encourage promising young scientists to enter or continue in the ALS research field. Fellows work with a senior mentor and receive extensive exposure to the ALS research community through meetings and presentations.

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