Curiosity and the Pursuit of Scientific Discovery: Q&A with Alex Lee, PhD

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.

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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. 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.