By Leo Barolo
Small changes in our genome can determine our risk to develop certain types of diseases. How these genetic risk factors exert function is still largely unclear. Dr. Valentina Lo Sardo’s lab in the Department of Cell and Regenerative Biology investigates how non-coding genetic risk factors affect cell state, fate, and ultimately, function. Her lab focuses on common genetic variants present in the non-coding part of the human genome to understand how they can increase risk for common diseases.
Dr. Lo Sardo is originally from Sicily, Italy and moved to UW-Madison in September 2020 after completing her postdoctoral studies at the Scripps Research Institute in California. She also recently joined CGSI as an affiliate member. Here she shares a bit of her trajectory and research:
Please give us an overview of your lab’s research interests and program.
We are particularly interested in understanding non-coding genetic risk for cardiovascular disease and how they can change the vascular wall homeostasis and eventually contribute to disease. Cardiovascular disease is not our only interest, we apply our interest in addressing functional genomics to other areas of human biology, including genomic diversity, the evolution of non-coding regions, but also other pathological conditions, like cancer.
Our approach is based on the use of induced pluripotent stem cells (iPSCs), an amazing tool that offers a multitude of opportunities to study human-specific functional genomics at the cellular and molecular levels. We use patient-specific iPSCs and genome editing to address how genetic variants affect different cell types, in a very controlled manner. Our approach allows for directly studying genotype to phenotype interactions. We are particularly fascinated by the non-coding part of the human genome, once called “junk DNA”. Now, we know that portion is extremely important, not “junk” at all. It’s also the most abundant, accounting for about 98% of the genome and the most divergent across species.
The overall interest of the lab and what I hope my lab will contribute to is understanding disease susceptibility driven by genetic risk factors, why it happens, how it happens, and how we can prevent disease occurrence by studying basic pathological mechanisms that lead to disease
What led you to get interested in this area?
I’ve been always fascinated by the amazing potential of stem cells, and pluripotent stem cells in particular. My initial encounter with stem cells was with murine embryonic stem cells to study a genetic neurodegenerative disease, called Huntington Disease. This is a monogenic disease, where just one gene mutation is enough to cause disease development.
Over time, driven by the fascinating discoveries I made and contributed to in this field, I was attracted to use stem cells to study more complex genetic phenomena and use this approach to understand genetic risk factors and particularly those residing in gene desert regions of our genome. The genetics of risk factors is complex. These are variants present largely in the population, that may or may not cause disease, so it’s definitely a harder task to understand genotype to phenotype interactions. We need the right tools and models and to test the right hypothesis to try to dissect their function.
I think we have tools and ideas in our hands to be able to address some very fascinating questions in basic research of non-coding genetic variants but also a good asset to transfer our knowledge in a translational paradigm and understand how to prevent genetic risk for common diseases.
Is there a single person or experience that most influenced your trajectory to where you are today?
I think my story is a beautiful patchwork of personal and professional relationships I was extremely lucky to collect in my journey. My parents were both doctors and extremely passionate about their work. I’ve always felt inspired by their devotion and commitment. My interest in science started young, when I was always wondering how medicine could become more precise, individualized and, most of all, preventive. My parents were both oncologists and listening to them talking about many cases, I’ve always wondered how we can understand disease at the cellular and molecular level, to prevent disease and spare people suffering.
I had also great mentors along the way. My Ph.D. and postdoc mentors are both very successful women in science and this was definitely an incredible inspiration for me. I had the great privilege to be surrounded by incredible collaborators and scientific communities, extremely vibrant, both in Milan and San Diego. Now I’m happy to have kept this line of commitment and to be able to do my independent research at UW-Madison with so many fantastic colleagues.
Do you have any hobbies?
I like cooking a lot. When I was an undergrad, someone told me that if you are good at cooking you’ll also be good at science, meaning that if you can follow a recipe for cooking, you can also follow a protocol in the lab. I partially agree, but I think science is very much like cooking. Yes, you must be meticulous to follow a protocol for the success of your recipe/experiment, but most of the time, to make a recipe fully yours, you have to change things, add ingredients, and flavors to make it better, to be unique. I think about science this way sometimes. You have to be rigorous, but you also have to allow your imagination and your ideas to take over and bring them to the next level. This is a great recipe!
Dr. Lo Sardo believes that she was deeply influenced by meeting people from all over the world. She hopes to fill her lab with people with diverse backgrounds. Additionally, she hopes her work will contribute to functionally annotating the unknown part of the human genome and to identify how genetic variants can impact specific cellular processes and lead to disease. The lab aims to contribute to individualized medicine, building a predictive and preventive approach for common human diseases.