Tina DaSilva, Executive Director of Research Operations met with Valerie Gouon-Evans to learn about her transformative work in the Center for Regenerative Medicine, CReM. Take a look at Valerie’s path that led her to liver research.
Can you provide an overview of your research background and your specific area of focus within the field of regenerative medicine?
I am a PharmD PhD, graduated from Universities of Paris in France. My research career within the field of regenerative medicine started when I joined Dr. Gordon Keller’s lab as an instructor. Gordon is one of the pioneers who created protocols to culture and differentiate pluripotent stem cells (PSC) to generate various cell types of the body. My job was to make liver cells. I still have the vivid memory of thawing the first available and costly human embryonic stem cell line H1. It took us a few weeks to finally see sparse colonies emerging in the dish. That was way before the era of commercialized Kits to grow and differentiate PSCs!
My seminal work was published in Nature Biotechnology where I identify BMP4 as an essential factor to induce the liver program in a dish, a protocol that is now widely utilized to generate liver cells from any PSCs. I then established my lab at Icahn School of Medicine at Mount Sinai, NYC, with a focus on investigating the mechanisms that drive liver development using the PSC system and the mouse embryo.
When I joined BU in 2017, I decided to leverage our developmental findings to develop strategies to improve liver regeneration that would treat liver diseases. To do so, I collaborated with Dr. Drew Weissman at UPenn who pioneered with Dr Katalin Kariko the modifications of mRNA to render mRNA more stable and thus usable for therapy. Dr. Weissman provided us with mRNA encapsulated in lipid nanoparticles (mRNA-LNP) encoding many liver regenerative factors. That was before the worldwide fame and safety demonstration of mRNA-LNP-based vaccines against COVID-19. Since my lab has established mRNA-LNP as a safe tool to deliver regenerative factors in the liver to treat chronic and acute liver diseases in mice as well as to drastically harness cell therapy for liver diseases with primary liver cells and iPSC-derived liver cells.
What motivated you to pursue research in the field of regenerative medicine and what interests you most about it?
Given my PharmD background, I always had a strong desire to translate my research to the clinic. Liver regeneration became my passion. The liver is the only organ that can fully regrow after partial resection. However, the mechanisms or self-regeneration are exhausted during chronic damage or severe intoxication. Currently, my lab’s goal is focused on regenerative medicine to overcome this issue. We investigate strategies to harness naturally occurring liver repair mechanisms to produce more of the functional cells of the liver, the hepatocytes by either inducing their expansion or by promoting conversion of the biliary duct cells to hepatocytes, as well as harnessing cell engraftment for cell therapy. Liver cell plasticity between hepatocytes and biliary duct cells is a fascinating topic that my lab leverages and therapeutically facilitates to regenerate the missing liver cells based on the liver disease.
How do you see your research contributing to advancements in regenerative medicine and potential clinical applications?
My lab has established mRNA-LNP as a unique tool to advance regenerative medicine to find new cures for the liver diseases. Depending on the mechanism of regeneration targeted and the regeneration factor delivered with mRNA-LNP, our studies in mice, show that we can revert accumulation of fat in liver cells, known as steatosis, as well as fibrosis, two hallmarks of the liver disease. If translated to the clinic, my hope is that it would prevent the progression of the liver disease, and hopefully revert it as seen in mice. Our strategy is also able to accelerate liver regeneration after the acute acetaminophen-induced liver intoxication in mice. If translated to the clinic, we could treat and even save overdosed patients that come late to the clinic and for which the standard-of-care N acetyl cysteine is not efficient anymore.
Collaboration is crucial in research. Can you discuss any collaborative efforts you have been part of within the Center for Regenerative Medicine or with external partners? What were the benefits of those collaborations?
This is so true; collaborations are key for success in science. With the fast-growing technology, individual labs cannot catch up with the continuously developing expertise. The CReM has built a nationally recognized hiPSC expertise. Dr. Andrew Wilson is one of my colleagues and collaborator at the CReM working on liver diseases, especially the liver disease of alpha 1 antitrypsin deficient patients. He has established a patient specific iPSC bank that we are using in our cell therapy studies. I have also established collaborations with outside investigators, Dr. Drew Weissman and Dr. Norbert Pardi from UPenn, experts in modified mRNA, Dr. Ron Weiss from MIT, expert in synthetic biology who built complex genetic circuits in our PSC for cell therapy, and Dr. Donghun Shin from University of Pittsburgh who uses zebrafish as an animal model incredibly amenable for genetic studies to investigate liver disease and repair. Those collaborations have been instrumental to advance my research and generate funding.
Funding is crucial to support research. Can you share your experience in securing research grants or other sources of funding? What strategies have you found effective in obtaining financial support for your work?
What I have learned is that creativity is not always the best way to secure funding. A fundable grant based on the NIH criteria is an innovative proposal whose preliminary data represent 2/3 of the work described. To satisfy these criteria, I found that collaborative grants that combine multiple expertise are the most successful. Foundation grants are also key to complement the NIH funding portfolio.
Communication and dissemination of research findings are essential. How do you engage with the scientific community and other stakeholders to share your research outcomes? Are there any notable publications, presentations, or collaborations you would like to highlight?
I attend at least 5 conferences a year where I give talks and regularly visit other institutions to share my lab studies. It is very important to me that all members of my lab share their work with the outside scientific community; they attend at least 2 meetings a year in addition to the Evans research day and institutional seminars. Another way to disseminate my science is through the BU Liver Biologist (BULB) group that I direct that brings together 13 labs from BU BMC and outside institutions. The mission of the BULB is to share expertise in the liver field and generate collaborative publications and funding. I would like to highlight our publications pioneering mRNA-LNP as a tool to deliver regenerative factors in the liver to treat liver diseases (Rizvi et al, PMID33504774, Nature Communication) (Everton et al., 2023, PMID37131727, BioRxiv, also submitted to Journal of hepatology) (Rizvi et al, 2023, PMID37131823, BioRxiv, also in revision in Cell Stem Cell), and our recent work on the delivery of regenerative factors via mRNA-LNP to robustly improve cell therapy for liver diseases (Smith et al., in preparation).
What inspired you to move to the United States?
It was my American dream! When I graduated in 1996, the next obvious step to pursue a career in research was to do a postdoctoral training in the United States, where research was well supported and the technology the most advanced. Nothing held me in France at that time and my parents were and are still my most unconditional career supporters. I am the first college generation in my close family. I have heard so many times from my dad, artist butcher at that time, “The daughter of the butcher can do as well as anybody else”. My parents instilled in me the courage and the freedom to reach my dreams. I am immensely proud of them and grateful for their continuous loving encouragements. The postdoctoral trip to US was supposed to be just for a few years, however, life led me to a different destiny. I got married, had 2 boys, now 17 and 22, and I’m still here, 26 years later! I don’t dream anymore. I am fully experiencing a passionate scientist life.
To learn more about Dr. Valerie Gouon-Evans, and her research email her at valerige@bu.edu.
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