Alex Lee, PhD, a bioinformatician in the Sweet-Cordero lab, recently received an R50 training grant from the NCI. This salary-based award, which received a perfect score from reviewers, will allow Lee to explore additional research interests and collaborate with other labs in addition to his regular responsibilities.
Below, Lee talks about his childhood love of science, the wisdom of colleagues, and how he spends his free time. Hint: family time and biohacking anything!
Q. Before we talk about your research and career, let’s talk about you. Where did you grow up? If not from the Bay Area, what brought you to UCSF?
A. I grew up in the San Gabriel Valley suburbs of Southern California. In fact, I met my wife during high school there, and we've been together ever since. We both came up to the Bay Area to do our postdocs at Stanford and fell in love with the area and its culture, which led us to stay.
Coming to UCSF was an excellent career decision, though it happened more through serendipity than planning. The Sweet-Cordero Lab, where I work now, was originally based at Stanford, and when my PI was recruited to UCSF in 2016, I made the move as well.
Q. What put you on the path to a scientific career and when? Who and what were your influences growing up that nudged you toward your chosen field?
A. I've wanted to be a scientist for as long as I can remember. As a kid, I loved browsing astronomy magazines in the library. Growing up with limited resources, I had to figure out a lot on my own, including setting up my own little chemistry lab. One time, I made hydrogen using lye (drain opener) and managed to burn my fingers—though at the time, I found it amusing because it made my fingers slippery!
Later, I discovered that I also enjoyed coding. In elementary school, we had a device to teach typing, and I soon hacked into the BIOS and started experimenting with basic programming. When school let out, I no longer had access to that device and didn’t get a PC until late in high school, where I continued teaching myself.
However, it didn’t even occur to me that bioinformatics—a blend of biology and coding—was a field. That opportunity only came when I was midway through my postdoc. That’s when I decided to completely shift my focus from bench science in neuroscience studying stress to bioinformatics in oncology.
Q. Tell us about your work? What is your primary focus these days? What motivates you to pursue the questions you ask?
A. My primary focus is studying the molecular biology of cancer, primarily pediatric cancers. We utilize diverse high-throughput data, including genomic, transcriptomic, epigenetic, single-cell, spatial, among other molecular modalities. I think of my work in two layers. The first layer is exploratory and rooted in basic science. We use computational and statistical methods to analyze genomic datasets of all sizes. “Large” might mean data from tens of thousands of samples, while “small” could involve a single experiment in a petri dish. Each approach has unique advantages. However, the end goal is generally to understand or explain a phenomenon that could ultimately lead to better therapeutics.
The second layer involves applying what we learn to make a direct impact on patients. Here, we use every available resource—from specialized algorithms to public datasets—to derive insights that can guide treatment for individual patients.
My work is deeply satisfying. For one, I enjoy coding and data mining and would be doing it in my spare time even if I weren’t paid for it. One great thing about bioinformatics is that, unlike bench science, when I have an idea or hypothesis, I can often test it in hours or days instead of months or years, and without the need for massive resources. Then there’s the curiosity and pursuit of scientific discovery, and most important for me, is the real-world impact we can make when our work goes beyond publications and contribute to meaningful patient outcomes.
Q. Let’s talk about your new R50. First, congratulations on receiving such a competitive award. What will the grant enable you to do that might not be possible otherwise? How did working with Dr. Sweet-Cordero help with this?
A. Thank you. The R50 grant is a salary-based award, meaning it will support my salary for the next five years. This provides me with the freedom, beyond my primary responsibilities in the Sweet-Cordero lab, to explore additional research interests and collaborate with other labs. For example, I'm currently collaborating with at least seven other labs, including several at UCSF. The Sweet-Cordero lab is the foundation and what laid the groundwork for this grant. The lab’s exceptional NCI grants and projects enabled us to develop a highly competitive experimental approach, making this award possible.
Q. Your application earned an impact score of ten. What does this mean?
A: In NIH grant review, at least three reviewers evaluate each application across multiple criteria, including significance, investigators, innovation, approach, and environment. Each criterion is scored from 1 to 9, with 1 being exceptional and 9 being poor, so lower scores are better. After discussing the application, each reviewer assigns an overall impact score. The final impact score is calculated by averaging these overall scores from all eligible reviewers and then multiplying by 10.
An impact score of 10 is considered a “perfect score,” indicating that all reviewers consistently rated the proposal at the highest level across all categories, reflecting a strong endorsement of the proposal’s overall quality and potential impact.
Q. For colleagues who might be thinking about applying for this type of grant and others, what advice can you offer? What was the process like?
A: This type of grant is different from traditional grants, which are mostly based on experimental approach and design. Here, while a strong approach and design are still essential, it’s also important to highlight past accomplishments and outline a future direction that logically ties to your proposed project.
It’s crucial to convey both your ability to work independently and your commitment to collaboration. While it can be tempting to dive deep into the details of your work, remember that reviewers have many applications to read. So, instead of overwhelming them with excessive details, focus on making your proposal clear and easy to follow. Make sure to work closely with your mentor and seek feedback from as many people as possible, including those outside your field. This can provide fresh perspectives and help make the application accessible to a broader audience.
Lastly, I'll leave you with Hemingway's wisdom: "The first draft of anything is shit." So just write and write, recursively making it better, and never get bogged down.
Q. What resources did you use to write the grant, if any?
I think the most valuable resources were my colleagues and the people around me. I had them read multiple versions of my application and asked for feedback constantly. It’s also advisable, especially early on, to reach out to people who have applied for similar grants and ask for their advice—even those who weren’t successful can offer valuable insights. On the NIH portal you can find prior recipients.
Q. Where do you see yourself and career in five and ten years?
A. I see myself doing much of the same work but hopefully on an even larger scale. I really enjoy my field and can’t imagine being in any other. I also plan to apply for additional grants, particularly to support computational hardware, as the demand for resources is growing rapidly with the exponential advances in high-throughput technology.
Q. What are your pastimes and pursuits outside of work?
A: In my free time, I like to spend as much time as I can with my son and wife. When I do have a moment to myself, I enjoy data mining and coding to explore topics I normally don’t have time for or that fall outside my main specialty. This could mean coding up a fun tool or poking around the genome for additional insights.
I also like reading pop science, especially in fields like physics. Sometimes I like to just wander around the library and pick out random topics. Every day, though, I make time for meditation (recently I’ve also been having fun with my new fNIRS biofeedback device), jogging, and weights. I also enjoy exploring health innovations and consider myself a bit of a biohacker—anything from intermittent fasting to cold showers is fair game.