National Postdoc Appreciation Week at BCM: Meet Dr. Hanfeng Lin
From the Labs joins the celebration of the 2026 National Postdoc Appreciation Week at Baylor College of Medicine by featuring Dr. Hanfeng Lin a postdoc in Dr. Jin Wang’s lab.
From the Labs sat with Dr. Lin to learn about his postdoctoral experience and his evolution as a researcher as he ventured beyond his original training to solve unanticipated scientific questions.
FTL: What led you to choose this area of research for your postdoctoral work and specifically the lab you are in at Baylor?
HL: I came into this project from structural biology. Before joining Baylor, I was purifying CRISPR-associated proteins and solving crystal structures, and at the time getting a single structure was the achievement – but it could take years. Then AlphaFold arrived, right as I was starting my Ph.D. here, and it reframed the whole question for me.
If structures were about to become cheap and abundant, the interesting problem was no longer how to obtain one, but what to do with it: how do you use a structure to make a drug? That is what moved me toward drug discovery.
Targeted protein degradation (TPD) was the natural landing point. A PROTAC or a molecular glue does not just bind one protein: it forces two proteins to interact into a ternary complex, and whether that complex forms well is what decides if the drug works. That is a genuinely harder structural problem than a single binding pocket, but it is still a tractable one: three components and a defined interface is something you can model and test. Complex enough to be worth the effort, bound enough to actually get somewhere. I joined Dr. Jin Wang’s lab in the Chemical, Physical and Structural Biology (CPSB) program because it was one of the few places where I could model that complex, make the compound and then run the proteomics to see what it really did in a cell – all in the same lab. When I finished my Ph.D. in December 2025, staying on as a postdoc was an easy decision; the molecular glue field was just opening up and I wanted to see it through.
FTL: When you are talking with people outside research, how do you explain your work and its importance?
HL: I tell people that every cell has its own recycling system, and my job is to design small molecules that act like a piece of double-sided tape. One side sticks to the cell’s garbage-tagging machinery, the other side sticks to a disease-causing protein, and once the two are glued together the cell destroys that protein on its own. The appealing part is that most human proteins cannot be blocked by conventional drugs – they have no pocket for a drug to sit in – but you do not need a pocket to glue something.
The catch is that nobody could reliably predict which proteins would respond to which glue. Most of my work has been building the screening and computational tools that turn that guesswork into something systematic.
FTL: Were there specific techniques you had to master for this work? If so, what resources at BCM did you draw on to learn these?
HL: Two, and they sit at opposite ends of the lab. The first is ultra-high-throughput quantitative proteomics – measuring more than 7,000 proteins at once, across hundreds of samples, so we see everything a compound does rather than only what we hoped it would do. I learned mass spectrometry largely with Dr. Sung Yun Jung at BCM Mass Spectrometry Proteomics Core, who were generous with both instrument time and troubleshooting. Startup funding from BCM’s Center for NextGen Therapeutics later allowed our lab to bring in a state-of-the-art Orbitrap Astral mass spectrometer, and together with the help from Thermo Fisher Scientifics, we built a workflow around it that runs roughly 300 samples a day.
The second is computational structural biology: molecular dynamics, quantum chemistry and more recently AI structure prediction. My CPSB coursework in molecular biophysics and computation gave me the foundation, and a Leadership Resource Allocation on the Texas Advanced Computing Center’s supercomputers gave me somewhere to run it.
FTL: Are there any moments from your work on this project that particularly stand out either as an exciting discovery or a specific challenge/roadblock you had to overcome?
HL: The exciting moment was realizing our lead compound was degrading VAV1, an immune signaling protein that had never been reported as a target for this class of drug, and that the part of VAV1 being recognized did not match the sequence motif the entire field assumed was required. My first reaction was that it had to be an artifact. It took a new structural model, built with a pipeline I wrote called GluePlex, to see what was happening: the compound and the protein were meeting through an interaction nobody had anticipated, anchored by a single arginine residue stacking against the drug’s indole ring. Mutating that one residue abolished degradation, and the model held up.
The roadblock came earlier, and it was humbling. We kept seeing degradation signals that were not real and eventually traced them to our own measurement tool – the luminescent tags everyone uses to monitor protein degradation contain lysine residues, so the tag itself was being marked for destruction.
We rebuilt the reporters without any lysines, which fixed our assay and turned into a short paper and a book chapter that many labs now use. Losing months to an artifact is frustrating but characterizing it properly ended up being more useful than the result we originally wanted.
FTL: How has being at Baylor helped you overcome obstacles during your time as a postdoc?
HL: Mostly through proximity to people who know things I do not. When you have some great ideas about new molecule design, you can always find chemists who are willing to discuss synthesis feasibility. When a mass-spec method was not behaving, core staff would sit down with the raw files. Baylor’s institutional investment mattered, too. Without the Center for NextGen Therapeutics startup support, our lab would not have the instrument that makes screening at this scale possible, and the VAV1 project would not exist in its current form. Being in the Texas Medical Center also means the clinical relevance of a target is never an abstract question; someone nearby treats those patients.
FTL: Has being at Baylor opened unexpected possibilities for your professional development?
HL: Very much, and mostly in directions I did not plan. I arrived as a wet-lab chemist and have gradually become half computational scientist – running simulations at TACC, performing co-folding experiments, and this year building GlueMiner, a full-stack web database of molecular glue compounds and their degradation targets, from the database schema to the deployed site. I would not have predicted that.
Baylor also pushed me to present well outside my comfort zone, and all this led to receiving the Ruth McLean Bowman Bowers Excellence in Research Award. Those experiences did more for my scientific communication than any course could have.
FTL: What are your future career plans and how did working on this project contribute to your goals?
HL: I am looking to move into drug discovery in industry, and I am especially drawn to early stage biotech. Small companies cannot afford a specialist for every step; they need people who can cross domains – design the compound, run the proteomics that say whether it worked, model the structure that explains why and then build the software infrastructure that makes the whole thing reproducible. My training has been deliberately hybrid in exactly that way, wet lab and dry lab in the same pair of hands, which I think makes me a good fit for that environment. The VAV1 project was an end-to-end exercise in it: an unbiased screen led to an unexpected target, computational modeling explained the mechanism and that mechanism directly guided the chemistry that improved the molecule. That loop from data to hypothesis to a better compound, is the job I want to keep doing.
FTL: What are your favorite things to do outside the lab? Has living in the Houston area helped you enjoy those activities?
HL: Anime, video games and piano, in whatever order the week allows. Piano is the one that resets my brain: after a day of staring at data, short practice is the only thing that reliably clears it.
Houston has been unexpectedly good for the rest: there is a real anime community here, including a large annual convention, and enough Asian bookstores, groceries, and restaurants that it never feels far from home.
FTL: Would you like to add anything else?
HL: Only that “Postdoc” can sound like a holding pattern, and it has been the opposite for me. In the past year I have published work I am proud of, learned a programming stack I did not know existed, and watched a result I was sure was an artifact turn into the most interesting thing I have found.
I am grateful to Dr. Jin Wang for letting me chase questions well outside my original job description, and to the lab members and core staff who made the work possible.
Thank you, Dr. Lin, for sharing your fascinating experience! We wish you the best in your future endeavors.
Interested in reading Dr. Lin’s latest paper in Nature Communications titled “Leveraging high-throughput proteomics and AI-based protein folding to accelerate VAV1 molecular glue discovery“? Follow this link.
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