About Dr Anna Baulies Domenech

Dr Anna Baulies Domenech is the research area scientific lead for metabolism at Abcam. She completed her PhD at Universitat de Barcelona before undertaking postdoctoral research at CIBER and the Francis Crick Institute.

Tell me about your research experience. What initially drew you to a career in science, and what made you interested in stem cell and metabolism research?

I’m an Organic Chemist by degree. I’ve always been very interested in answering all sorts of questions, and my curiosity for life sciences started at a very early age. I just loved any kind of knowledge that would help me understand the world. I decided to study chemistry as it has a very good balance between theoretical and methodical research. During the last years of my degree, I worked in the inorganic synthesis lab, organic chemistry, and finally, I signed up for a one-year program of Biochemistry in the lab offered by my university. This helped me decide to pursue a Master's in Biomedical Sciences. There, I truly discovered my passion for having an impact on society by solving problems that could develop new therapies and help patients.

At that time, my dad was undergoing chemotherapy treatment for liver cancer diagnosed two years earlier. I decided to pursue a PhD in the field of liver disease and metabolism, focusing on hepatocellular carcinoma, with a fellowship funded by the government. During that time, I applied for a mobility fellowship offered by Boehringer, which allowed me to stay for one year at the Keck School of Medicine in LA, in the laboratory of Neil Kaplowitz, one of the key opinion leaders in drug toxicity and liver injury. When I finished my PhD, I had a broad understanding of injury-recovery mechanisms, which, when aberrant, lead to cancer. I wanted to expand my knowledge on how these mechanisms work in stem cells, which are the origin of many cancers, and at that time, organoids in research were having a massive boom. I joined the Stem Cell and Cancer laboratory at The Francis Crick Institute in London, where I studied stem cell fate decisions and injury-recovery models linked to cellular and metabolic plasticity in the intestine. There, I discovered a chemotherapy-resistant population in colorectal cancer.

Can you give an overview of the current landscape of research into stem cells and cellular plasticity in cancer?

It is a fast-evolving field, especially with the emergence and improvement of new technologies such as single-cell RNAseq and spatial transcriptomics, metabolomics, and spatial IHC. Big data and data integration initiatives, such as the TRACERx study, are transforming our understanding of cancer evolution by integrating clinical, histopathological, and genomic data. CRISPR has also had a massive impact on the field, allowing for the fast generation of knockout (KO) models in stem cell populations (which is very challenging otherwise) and the generation of tracing models to label and follow these populations in metastatic models, for instance. CRISPR screenings in cancer cell lines linked to animal models are also shaping new biomarker and therapeutic discovery pipelines and are already having an impact on patient treatments. The fact that cell therapies and genetic targeting for rare diseases are reaching the clinic means that a new revolution in patient care is on the horizon.

Metabolic plasticity is also gaining more and more attention. I feel that metabolism has always been seen as a very traditional discipline, but now, with the emergence of tools to detect metabolites (such as immunometabolism flow cytometry panels) and the fact that resistant cancer populations have massive metabolic advantages (one of my papers from my PhD already linked cancer cells to metabolic adaptation to oxidative stress and treatment!), the field is gaining a lot of interest. This is also very closely linked to research in aging, where stem cells are being deeply studied in all these new emerging research centers with cutting-edge technologies such as Altos Labs, the Institute of Human Biology, or Calico Labs.

What are the biggest challenges your research field faces today?

Like any other field, funding is always an issue. Technologies are evolving rapidly, becoming more expensive, and require highly qualified scientists to operate them, which further increases costs. Additionally, Brexit has had a significant impact on both funding and the availability of highly trained workers, although there have been government programs to compensate for some of the losses. Recent cuts to NIH funding will have a clear long-term impact on this and other fields.

When focusing more on human stem cell research and the potential for human therapies, we need to consider ethical issues related to the type of material used (such as embryonic stem cell research) and the regulatory hurdles surrounding the use of materials in laboratories and patient consents. Nowadays, there are many protection systems in place, but more work needs to be done to train researchers on these topics.

What do you think the future holds for the field? Are there any upcoming developments you're excited for?

For this question, I would like to focus on targeted therapies and resistant populations. With the emergence of all these new technologies mentioned before, we are in a much better position to detect very small and normally missed or overlooked populations that confer resistance to chemotherapy treatments. What we know now is that there is a regenerative component in them, normally linked to fetal development, and they have a massive plastic capacity to adapt to all sorts of cues. The characterization of these populations is becoming more defined thanks to omics data, new tools, and collaborative efforts. I have a paper from my postdoctoral studies that is now under revision in a very prestigious journal; hopefully, I can share more about this soon!

What changed in stem cell research during your time in academia?

Since I started working as a scientist, I have witnessed a massive development in understanding how cells adapt to injury or stressful cues, which has shaped much of the understanding we have today. This knowledge helps predict or understand how cells will behave under specific conditions. I can't deny the potential of AI; it might be powerful if implemented properly and it can benefit from the various mathematical models generated by the stem cell community to predict why a cell will divide or become an enterocyte, for instance. This knowledge can be applied to predict how a cell can respond to a certain therapy or which cues might generate a certain mutation.

I can't forget to mention the influence of the environment, immune cells, metabolites, and oxidative stress factors on cellular behavior. The use of integrated patient-derived organoids, together with more complex matrices (including other cellular components, metabolites, and factors), and the revolution of organ-on-a-chip devices, combined with AI discoveries, will massively shape the therapeutic potential of stem cell research in the upcoming years.

What motivated you to transition from research to a role at Abcam?

I was ready to see a more direct application of the work I was carrying out, and I had this great opportunity to champion a research area that I love, applying all my scientific and technical knowledge while also understanding customer needs very well (I was a customer just a year ago!). I felt that the role had the perfect combination of factors. In academia, the next step after a postdoc is quite narrow. You either become a Principal Investigator and develop your own research or seek a more stable position as a research assistant or lab manager.

The Abcam Talent Acquisition team contacted me through LinkedIn to ask whether I would be interested in applying for the position. At the same time, I was undergoing interviews for a grant that would help start my independent journey. A few weeks after joining Abcam, I found out that I had scored second for the grant out of hundreds of applicants, but I didn't get it. It didn't matter because I had already decided to join Abcam, but it made me realize how hard and competitive science can be when seeking funding.

Another challenge of staying in academia is the long working hours that are expected, and the fact that many networking events happen in the evenings, and women tend to be underrepresented. Additionally, if you have, let's say, 10 years from the PhD to apply for grants at the junior level, it is very challenging to balance this with starting a family. I had two kids during my postdoc and working in the lab while pregnant is quite hard sometimes (and some experiments you can't perform due to hazard issues). Although I felt well supported at The Crick thanks to the collaborative network, our amazing lab manager, and the team, not everyone is that lucky. It is difficult for women to keep up at the same level as men or women who don't have kids. Grants give you a few months' extensions per child, but realistically, it is very challenging to be at the same level as people who didn't take a break.

What do you do at Abcam? How does it relate to your work before and how does it differ?

I am very surprised by how similar the work can be in many ways, but of course without the bench component. At Abcam, I oversee new product development for reagents related to the field of metabolism. I am the main point of contact for the technical perspective of those reagents and closely monitor data analysis and review when the product is undergoing the final steps before publication (I like to say, before they are released to the wild!). Data integrity and quality are key at Abcam, and Research Area Leads work hard to ensure those standards are met.

We are also involved in process improvement of workflows, some related to the pipeline, others very technical and scientific. In a similar way to my work in the lab, we collaborate with research area scientists in troubleshooting and finding better ways to perform data validations. Additionally, much like my role as a researcher, I seek collaborations when there is a specific need for a sample type or for more challenging targets where we need help to develop the product. This often requires specific knowledge of a particular protein that we may not have, but another lab might.

I am also involved in internal data analysis that leads to decision trees in product development. While it is not an analysis of an RNAseq data package as I would do before, both types of analysis lead to interesting results that can be applied later on in projects.

What skills or knowledge from your academic career have been most valuable in your role now?

An analytical mindset and attention to detail are crucial, as they enable me to quickly analyze large data packages prepared by others. My eyes and brain are trained to identify compelling data and easily detect when things are not coordinated or functioning as they should. Literature knowledge is also very useful, as I need to answer all sorts of scientific queries in a fast-paced environment. If I don't know the answer, I know where to find the information and can quickly extract it, which is directly related to being trained in extracting key points from large data packages, such as a paper or a single-cell RNAseq dataset.

Other skills I'd like to highlight include out-of-the-box thinking and originality, which are more artistic skills but very helpful for problem-solving. One of the most important skill you train as a scientist is communication, including summarizing data, preparing presentations, and delivering them convincingly. Finally, I would emphasize the collaborative mindset. Without collaboration, there is no progression in science. Generating knowledge is a complex task and can be overwhelming as an individual, and everyone's mind processes knowledge differently. Getting the most out of everyone is key to moving research forward and producing results and data in a more competitive and reliable manner.

What advice would you give to young scientists interested in pursuing a career in stem cell research?

At the beginning, especially during the PhD, the learning curve is quite steep and can feel overwhelming. A colleague at that time, and now a very close friend, gave me a magnet (14 years ago!) that has been on all the benches I have worked at (it even went to LA!). It said: "Never, never, never give up." I didn’t know at that time that it was a quote from Winston Churchill, just like I didn’t know I would end up living in the UK and becoming a British citizen! But what I found very motivational was the importance of perseverance and determination. Scientific careers are a lot about failing, wrong hypotheses, no changes, negative results, and the feeling of accomplishment is normally absent. It is very important to keep asking questions, designing experiments, trying new ideas, and eventually, you have that eureka moment! All that data that seemed negative was there for a reason, and things take on a new shape.

One day, during the postdoc, after a very bad month of experiments in the lab, a colleague wrote "Chocolate" underneath the quote: "Never, never, never give up Chocolate," to remind me that sometimes it’s good to stop insisting when things don’t work out. It’s more about determination than stubbornness, and chocolate is always an option!

How did you stay motivated and inspired in your research?

I am a very passionate individual; everything related to new knowledge excites me and makes me feel grounded. Attending conferences, networking events, and listening to talks in fields completely different from yours can provide inspiration and motivation. I highly recommend finding a good mentor outside your immediate network to gain perspective on your career. Asking questions is also very important; it took me a few years to understand that, and even now, I sometimes need to remind myself.

What I see nowadays is a constant flow of information. Young researchers are more in contact with biotech, entrepreneurship, and other opportunities outside the strict academic career, which is really positive. These interactions also help to feed your research if you want to stay in academia.

Can you share a memorable moment, learning or breakthrough from your career that significantly impacted you?

Yes, I had two key moments that I will never forget. The first one was during my PhD. I was performing drug toxicity experiments in fasted animals, and one day I had a large cohort but forgot to remove the food before starting the experiment. When I analyzed the data, I discovered that the interaction of the two drugs was mimicking a fasting state, which set the grounds for the mechanism we later published. This finding was very relevant in the field, especially for pediatric patients.

The second moment was during my postdoctoral studies. Through a collaboration, we were trying to describe a stem cell population observed in an animal model that seemed to be relevant in intestinal stem cells. After analyzing a significant amount of data, I had the idea to check all the slides of mice cancer models stored in the lab, as I had a gut feeling that these cells would be present in tumors and might play a role in tumor resistance. Everyone thought this was irrelevant, even my PI at the time, but I found THAT cell. I will never forget that moment in the dark confocal room! That discovery marked the beginning of a very nice piece of work that will be published soon.