10 Questions w/ Gene Yeo — Professor @ UCSD

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Gene Yeo is a Professor of Cellular & Molecular Medicine @ The University of California San Diego (UCSD), a founding member of the Institute for Genomic Medicine and member of the UCSD Stem Cell Program and Moores Cancer Center. Dr. Yeo has a BSc in Chemical Engineering and a BA in Economics from the University of Illinois, Urbana-Champaign, a Ph.D. in Computational Neuroscience from Massachusetts Institute of Technology and an MBA from the UCSD Rady School of Management.

Yeo is a computational and experimental scientist who has contributed to RNA biology and therapeutics. His primary research interest is in understanding the importance of RNA processing and the roles that RNA binding proteins (RBPs) play in development and disease. Since inception, Yeo’s lab has focused on uncovering molecular principles by which RBPs affect gene expression, how RBP- mediated post-transcriptional gene networks contribute to cellular homeostasis in stem cells and the brain, and how mutations in RBPs lead to human developmental and neurodegenerative disease. His lab pioneered computational algorithms and experimental methods in human disease-relevant systems to conduct systematic and large-scale studies. These multidisciplinary methods combine machine learning, biochemistry, molecular biology, genomics, chemistry and materials research. His lab develops methods that are systematic, robust and adoptable, such as enhanced CLIP for the purposes of large-scale mapping of protein-RNA interactions (Van Nostrand et al, Nature Methods, 2016). Gene’s lab is a major contributor of resources to study RBPs that enable hundreds of labs across many areas of bioscience, such as the world’s largest resource of RBP-specific antibodies that facilitated generation and interpretation of the most comprehensive maps of RBP-binding sites to date for hundreds of RBPs (Van Nostrand et al, Nature, 2020). They have also systematically uncovered RBPs that condense into RNA granules during stress and demonstrated strategies to leverage these for therapeutic use in neurodegeneration (Markmiller et al, Cell, 2018; Fang et al, Neuron, 2019; Wheeler et al, Nature Methods, 2020). His lab also demonstrated in vivo RNA targeting with CRISPR/Cas proteins (Nelles et al, Cell, 2016) with proof of concept in repeat expansion disorders (Batra et al, Cell, 2017; Batra et al, Nature Biomedical Engineering, 2020). Work from the Yeo lab has been highlighted in Nature Methods and Nature Reviews Genetics as “Method to Watch” and featured as a top story in Discover magazine in 2016. These efforts have led to clinical programs to develop medicines for RNA-related diseases.

Yeo has authored more than 200 peer-reviewed publications including invited book chapters and review articles in the areas of neurodegeneration, RNA processing, computational biology and stem cell models; and served as Editor on two books on the biology of RNA binding proteins. Gene is on the Editorial Boards of the journals Cell Reports, Cell Research and eLife, and on the Advisory Board of Review commons. Gene joined UCSD as an Assistant Professor in 2008, was promoted with tenure to Associate Professor in 2014 and to Professor in 2016. Gene was the first Crick-Jacobs Fellow at the Salk Institute (2005–2008) and is a recipient of the Alfred P Sloan Fellowship in recognition of his work in computational molecular biology (2011), Alpha Chi Sigma-Zeta Chapter Krug Lecturer (2016), Singapore National Research Foundation Visiting Investigatorship Award (2017), the inaugural Early Career Award from the International RNA Society (2017), the Blavatnik National Award Finalist (2018 & 2019), San Diego Xconomy Awardee for ‘Big Idea’ (2019) and 2019 recipient of the Highly Cited Researcher in Cross-Field category, recognizing the world’s most influential researchers of the past decade. Gene’s research has been funded by the National Institute of Health, National Science Foundation, California Institute for Regenerative Medicine, TargetALS, ALS Foundation, Department of Defense, Myotonic Dystrophy Association, Myotonic Dystrophy Foundation and Chan-Zuckerberg Initiative. Gene has also been funded and collaborates with biotech and pharmaceutical companies such as Takeda, Genentech and Roche.

Gene is a co-founder of biotech companies which includes Locana, Eclipse Bioinnovations, Enzerna, Proteona (acquired by Singleron) and Orbital Therapeutics. Gene played a critical role in the successful raising of $55M for Locana at series A (2019). Gene serves or had served on the scientific advisory boards of the Allen Institute of Immunology, Locana, Eclipse Bioinnovations, Proteona, Aquinnah, Cell Applications, Nugen (now Tecan), Sardona Therapeutics and Ribometrix. Gene is a senior advisor to Accelerator Life Sciences Partners.

Gene is the faculty founder of DASL (Diversity and Science Lecture Series, 2020) providing a voice for scientists to discuss diversity, equity and inclusion challenges and celebrating their scientific achievements. Gene was a Sword of Honor recipient (the highest honor) in Officer Cadet School in 1999 and has served in the Singapore Navy as a Naval officer. Gene has completed 2 full Ironman-distance and multiple half-ironman-, olympic-, sprint-distance triathlons, full marathons and half-marathons, but now spends time rock climbing.

We sat down with Gene Yeo to ask his viewpoints on everything from entrepreneurial lab culture, what he looks for in new research topics, to advice on building companies…

1

What advice would you give to founders working with University Tech Transfer looking to spinout out a company?

“University Tech Transfer can be an exceptional partner to amplify the value of research findings. My advice is to work closely with tech transfer on carefully timing the publications with the disclosures.”

2

Can you describe your process for vetting new ideas to pursue in your lab?

“I look for the intersection of strong technology opportunity, strong biology and then identify strong trainees that can marry the two.“

3

How do you establish an effective entrepreneurial lab culture?

“Promote risk-taking and build multi-disciplinary teams”

4

What advice would you give to professors trying to entrepreneurialize their labs?

“As an academic mentor, I try as much as possible to identify projects that fulfill both an academic mission by solving fundamental questions and also form opportunities for trainees to gain valuable skill sets and if successful, create commercial and career opportunities for the trainees and the lab“

5

Outside of academia, what is one seemingly random activity that helps make you a better researcher?

“Family. Family centers my worldview and forces me to be much more efficient with my time“

6

How do you identify the point at which a scientific discovery is ripe for commercialization?

“Personally, I do not think I do a good job identifying these points, but I try to work with the best people in the business to help me strategize and act as reality checks. That would be my advice, work with folks with much more experience than you. “

7

What advice can you give to academics raising their first round of venture funding?

“My advice is that it is important to identify venture partners that have more value to add than just capital. Different technologies need different amounts of runway and time to mature and not all venture firms have the same patience. Some technologies need a mixture of young academic teams and seasoned biotech managers to give them a chance and some investors understand that.

8

What advice would you give to business professionals looking to get in contact/help commercialize startups spinning out of academia?

“I believe it is helpful to have strong personal as well as professional relationships with the academic founders of the concepts and technologies that business professionals hope to leverage. My advice to business professionals would be to identify academic founders that are true, dependable partners.“

9

What advice would you give to professors in balancing founding a company and continuing to pursue academic research?

“My advice would be to prioritize your academic lines of inquiry as companies need to be very focused and narrow and as such they may be blindsided by the next generation of research. Founding companies can nevertheless be rewarding for your trainees and your academic ecosystem“

10

What has been the most helpful piece of advice you received throughout your career as an academic entrepreneur?

“NO one is irreplaceable.”

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❤️ Thanks Andrew Yashar for your help in putting this together :)

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