Judit Jimenez Sainz

Biochemist and Geneticist Judit Jimenez Sainz investigates the root causes of cancer

Meet Judit Jimenez Sainz, a biochemist and geneticist who investigates different pathways that lead to cancer at the Medical University of South Carolina. She recently started her own laboratory and her newly minted team is focusing on DNA repair proteins as well as the famous BRCA protein whose cell localization impacts cancer risk.

Besides being a new PI, Judit advocates for other scientists and the next generation of STEMM students. She has especially supported those who come from her home country of Spain and are currently living and working in the United States.

As part of the Homeward Bound Leadership Program, Judit has even lived in Antarctica for almost one month, a testament to her adventurous spirit and bravery. She was lucky enough to experience the surprising beauty of the ice tundra and develop new friendships that will last a lifetime.

Judit recently embraced her latest adventure by becoming a mom for the third time. We caught up with Judit to hear all about how she juggles her duties as a principal investigator and a new mom.

Can you please tell us about yourself and your roots?

I am originally from beautiful La Rioja in the north of Spain near Basque country. I grew up there until I was 17 and then I moved to the coast to Valencia to do my undergraduate studies.

Were you always interested in science, or did you have another career path in mind?

I have been interested in science since high school. I had really good teachers in my high school, in particular three ladies who I had for geology, biochemistry and biology. The three of them were very different but they were really passionate about science and the importance of science for our society and how science can answer many things. There was one teacher during middle school who used to take chalk and draw everywhere regarding cells and microorganisms. I admired him because of his passion for science.

How did your university/educational path look like?

When I finished high school in Spain, I had to pass the nationwide exam, and I thought about going into medicine but I liked the molecular details underlying human diseases. I spent my undergraduate studies and graduate school in Valencia. While in graduate school, I was moving around Europe quite a bit. I went to Germany for a little while and I was also in Paris and London. I stayed in London for a year and two months to finish a chapter of my dissertation, so my PhD was kind of a European PhD.

I am now in the United States, and I came here in 2013 to work in Dr. Ryan Jensen's lab in the Department of Therapeutic Radiology at Yale University. A year ago I started my own lab at the Medical University of South Carolina in Charleston, a beautiful city that reminds me of Valencia.

I was always interested in human diseases and how molecular biology can help understand human diseases in the laboratory. First, I got exposed to research through a small laboratory in my hometown that mainly analyzed food and water to try to grasp the microorganisms there.

I feel that understanding the details behind the disease is very important and that has been my motivation to this day. I have a few cases in my family of Parkinson's disease and that really drove me to start molecular biology, biochemistry and cellular biology. My family also has a few cases of breast cancer so I was very curious as well how different diseases could cluster together or could be totally unrelated. For example, patients with Parkinson's disease have less risk of general cancers but they have more risk of breast cancer in women. My PhD involved trying to understand a protein named PINK1 involved in Parkinson's disease patients that when mutated could have a role in breast cancer progression. PINK1 is a mitochondrial protein that regulates mitochondrial function and homeostasis.

Who was/is your biggest supporter?

My biggest supporters are my family. My parents have always been there for the ride with whatever I wanted to do - it didn't matter what. I am a first-generation higher education student in my family. That was really challenging for them because they did not know how to explore that. I always wanted to be in science, but I did not always want to be in biology. When I was in high school, I wanted to be an astronaut but when I asked around, I could not find any Spanish astronauts in the whole country. Now I think we finally have the first Spanish woman astronaut undergoing the course at the European Space Agency.

My other big support is my sister. She always says that I can do anything so I should just go and do it. My husband who I met back in Connecticut is another person who thinks I can do anything, even when I sometimes doubt myself. Then there are mentors, people like you [Nicole, the interviewer] who help me to keep working hard for the things that I care about in science like running my own lab and publishing papers.

Recently you became the principal investigator of your own laboratory. Can you please tell us about the research topics your team is working on?

My lab is working on the thread of gynecological cancers because firstly, I resonate as a woman, and second, because I think there is more care that needs to be in place for us. Breast and ovarian cancers kill around 800,000 people every year worldwide. There are about 200,000 new cases for breast cancer every year in United States, and the outcomes are not as great as we would like.

I also like to understand the intent of molecules, so I work with molecules involved in breast cancer called BRCA. You may have heard the case of Angelina Jolie. She has a harmful mutation in BRCA, which are supposed to repair DNA when it is damaged by UV radiation or other factors. This works the same as when your washing machine breaks, and you call someone to fix it.

Every day a normal human cell can experience up to 1,000,000 DNA changes or mutations but not every day do we develop a tumor. That is because we have many of those DNA repair machineries repairing the DNA changes. I want to understand how certain populations and certain mutations in BRCA increase cancer risk and how once the tumor is developed in patients, we can make them more susceptible to therapies with targeted drugs.

Now that we can easily sequence DNA, we see a ton of variation on BRCA genes. One in every four people that get sequenced have what is called a Variant of Uncertain Significance. (VUS) This is a variation related to the normal sequence of the genome, and we do not know if that is going to be a risk for disease or not. I am trying to understand the function of those variants that we do not know yet. If we look at databases for the BRCA genes I am studying, there are more than 20,000 variants and only 25% of those we know are pathogenic. That means we do not understand 15,000 of the variants. When a patient comes in the clinic either with a tumor or without a tumor, we do not know what to tell them if they have a VUS. If the patient does not have a tumor but that variant is nonfunctional, we have to classify that variant as deleterious or pathogenic. We mainly use functional assays to classify how well the BRCA for that patient is able to repair DNA.

We do not have the power to evaluate the 15,000 variants but we have the power to evaluate handfuls with a lot of detail. I am collaborating closely with clinicians to get samples from patients who are BRCA mutation carriers. We want to make sure that first, we are able to prevent a tumor by knowing if that variant is dangerous and then secondly, when we have a tumor with a deleterious variant, we want to be able to treat the tumor with targeted therapies and get a good response to the treatment. This approach could potentially save a lot of lives and help clinicians with the clinical diagnosis.

What do you consider the most important finding of your career to date?

My most important finding happened a few years back at Yale University. As I mentioned this BRCA protein repairs DNA and most of the time the DNA is in the nucleus of the cell. You have to picture the nucleus of the cell like a fried egg. The nucleus of the cell is the yolk, and most DNA of our cells is in the nucleus for BRCA to repair. Most people thought that when you have BRCA with a harmful mutation, it is because the protein mainly stays in the nucleus but does not do its job. What I was able to see is that some mutations, even with a small change to just a single amino acid, change the protein so it gets stuck, like getting stuck in the white of the egg. We now see that the pathology is not due to the protein mis-functioning but rather because that protein cannot travel or cannot be transported to the place where the damage is located. It is really a problem of transportation.

I still do not know why that is or how we can fix that to be able to help patients but that is where we are working in the lab. We need to understand how the transportation of this protein is being altered in certain mutations and certain patients and how we can modulate transport to help with more personalized treatment for these tumors.

You were the president of the Association of Spanish Scientists in the United States (ECUSA) and the Network of Spanish Scientists Abroad (RAICEX). Further, you led the Talent Attraction and Scientific Policy. How did you become involved with these associations?

I remember it was a winter in Connecticut, and it was very hard for me that year because I was in the middle of the postdoc and the experiments were not working. I wanted to see something else and explore other things but I was a bit stuck in my project. There was an event in New York from the Spanish Science Association New York Chapter, and I just took my car and drove to New York in a really bad winter storm and I went to El Centro Español-Queens for this gathering. It was a bit awkward at first because I did not know anyone there but if you know me, you know I like to mingle. I started talking to people and then they said they needed people for a program called E-Visibility where they record podcasts and do interviews to really cool scientists. I started with that and then I got involved in advisory and career development with virtual workshops.

After a while, I was leading teams in communication and career development, and we were doing pretty cool stuff like creating welcome packages for new people coming to the United States from Europe. We were helping people who wanted to get their international medical degree translated for an American medical degree, which is a bit different. Then the president of the association nominated me to be the next president and I served that term from 2021 to 2023. The Spanish Association of Scientists in the United States fits into a network of Spanish associations of scientists globally and I became the president as well of the whole network for eight months. I was very interested in science diplomacy and how as scientists we can help governments to guide their agenda and the society. As an association we provided help and guidance to change the Spanish laws around science by incorporating internationalization aspects such tenure track positions and better conditions for PhD students and postdocs.

As a former president, I am still involved and we have just had an event in New York for Santiago Ramón y Cajal, a Spanish Nobel Prize winner. We are commemorating the 125th anniversary of his first trip to the United States with a exhibition that will remain opened for a year at NYU Espacio de Culturas, so don’t miss it if you visit New York! He discovered and drew beautiful images of neurons and we consider him the father of neuroscience. You can find more information https://ecusa.es/ecusa-cajal-octubre-2024/. I was not expecting to do this kind of leadership and bringing all these people together and working on projects like, for example, making a white book about women in science from different countries.

Through the Homeward Bound Leadership Program HB5 you went to Antarctica to empower more women leaders in STEMM. What impressed you the most about this experience and what did you learn about yourself as a woman in STEMM?

Antarctica is amazing. I was not prepared for the sounds that you hear in Antarctica and the colors you can see beyond just white. Antarctica has many tonalities of white, blue and grey. My senses were not ready for that and so it was remarkable. Second, and I think maybe most important, was the community and being surrounded by almost one hundred women, all in STEMM. This was mind blowing, powerful and nurturing. We had an amazing crew as well on the ship who took care of us and taught us through our stay in Antarctica. However, we also had to sit with uncertainty and not knowing what was happening in the next minute because Antarctica weather conditions fluctuate a lot. Being on a ship with few commodities really prepares you for not knowing what is coming next. This really allowed for some inner exploration that was very powerful and very new to me. Being a mom of three and a researcher does not let you spend much time to sit in inner calm. I would say the three things to emphasize from my Antarctica trip are: the place, the people and then your inner power. Also, you have to be okay with fear.

Do you have any advice for people who want to follow in your footsteps and pursue a career in science?

Go for it and if you wish, I can be your cheerleader! You are going to find a few rocks in the way, but they are just rocks, so you look at the rocks and you learn from the rocks. Go for it and then contact the person who really inspires you with the questions that you have about their path and then keep going through that cycle of question and answer and do not hesitate to ask the same question over and over again. All questions are good questions. You have to share your passions, your motivations and your worries because you do not know what the other person can give you. Maybe a person who you did not consider suddenly becomes instrumental. We do science better because we are doing it together.

I am here because I was held up and encouraged by many people. You are going to have to work hard but people can help you to work hard, so do not worry about that.

Who, what, when, where & why?

Who?

- would you like to conduct research with if you had the chance?

I have two people. One is Margarita Salas, who I would say was the most famous and important woman PhD in biochemistry and molecular biology in Spain. She was the first scientific woman ever elected to the Royal Spanish Academy. She passed away five years ago so I will not be able to do research with her, but she was very instrumental in understanding the DNA replication process and basic molecular mechanisms of bacteria and phage. I had the great opportunity to meet her daughter and talk extensively about her mom, and last March I met one of her last mentees and we discussed extensively about her science and how cool it was to be in the lab of Margarita Salas.

The second person is Jane Goodall. She worked with chimpanzees, and she has been so persistent, inspiring and sweet and surrounded by many other researchers to try to understand very important behavior and cognition questions that can translate to humans.

What?

- do you like to do in your free time?

Now I have a family with three kids, so I love playing with them, exploring nature and watching movies. Reading is also my passion but now I read in small intervals when Greta, Frida and Bruno are sleeping. I also love exercising through Zumba or running and I love cooking. However, the most important one I think is just to be with people.

I like cooking because then I can have a gathering with people. I like exercising because I exercise with people. I love to be with human beings.

When?

- do you find inspiration for your research?

Every time I am outside the lab and not doing science I find inspiration for science. I also find inspiration in the lab, but they are different inspirations. Creative ideas come when I am taking a shower, playing or when I am in nature or biking or just talking to somebody. Persistence and hard work are mainly done in the lab and that is where we get the results.

Where?

- is your favorite travel destination?

It is Antarctica now. My second travel destination would be the moon.

Why?

- did you choose your specific research topic(s)?

First because I care about human diseases, and I care about understanding the molecular biology of human diseases to help patients. The second and more important reason is that I care about women's health and minimizing health disparities.

How?

- do you deal with setbacks?

Move on.

…or?

Attend a party or be the host?

If I am hosting a party, that is good. If I am going to a party, that is also good. Both are great as long as there is a party. If there is a party, Judit will be there.

Museum or movie theatre?

Museum theatre.

Sneakers or dress shoes?

Either as long as I am out of the house

Optimist or pessimist?

Optimist.

Ambition or comfort?

Ambition.

See the future or change the past?

See the future.

The interview was conducted by Nicole Kilian and has been edited and condensed for clarity.

Image sources: Judit Jimenez Sainz.