Insights From Immunologists: Professor Hsi-Hsien Lin

F4/80, clone CI:A3-1, is a well-characterized and extensively referenced macrophage and microglia marker. Recently, we had the honor of joining Professor Siamon Gordon, the father of F4/80, in celebrating its discovery over 40 years ago, alongside the past members of his lab who in the decades since have made significant contributions to macrophage research, and the scientific landscape as a whole.

We spoke to Professor Hsi-Hsien Lin, who worked as a postdoctoral researcher in Siamon’s lab, about his career to date. Hsi-Hsien initially cloned F4/80 and developed the F4/80 knockout mouse before expanding his interests to the molecular and functional characterization of the broader myeloid cell-associated receptor family. He is currently a professor in the Division of Microbiology and Immunology at Chang Gung University in Taiwan.

Bio-Rad (BR): When did you first become interested in a career in science?

Hsi-Hsien Lin (HHL): I had been interested in science since school and decided to do an undergraduate and master's degree in science in Taiwan before moving to the University of Tennessee for my PhD.

BR: How did you become specifically interested in macrophages?

HHL: I was doing my PhD in the U.S., where I was working on mouse genetics, and, just by accident, I cloned a gene that was unidentified at the time. We sequenced the gene, and there was no known homology; it was a completely unknown gene. By the time I had finished my study, there was a paper from Siamon’s lab about a newly identified protein, and when we looked at the sequence it was exactly the same. So basically, I cloned the F4/80 gene by accident!

Before that, I had never heard of macrophages, but of course from then I started to read a lot of papers. Luckily for me, I had made the F4/80 knockout mouse at the same time that I cloned the gene. So, I came to Siamon and asked, “What should I do with these mice?” and that’s how we met. After I graduated from my PhD, Siamon invited me over to Oxford and offered me a postdoc position.

BR: Can you describe a highlight from your career?

HHL: Cloning F4/80 was really the best part of the beginning of my career. That really kickstarted my interest in macrophages.

BR: Can you tell us about your current research/role?

HHL: Ever since I cloned the F4/80 gene, I have been interested in learning more about it and its related family of genes. With the completion of the Human Genome Project, we had access to all the gene sequences, and I was interested in looking at F4/80-like genes. We found other members of the same receptor family, such as EMR2 and EMR3. This group of markers belongs to a G-protein coupled receptor (GPCR) subfamily, which I have continued working on and that is my main interest. My lab focuses on deciphering the functions and regulation of these GPCR proteins.

BR: What advice would you give to early career scientists?

HHL: I would say just stay curious and follow your own interests. For example, I’m interested in this group of receptors. I start at an individual receptor, and if the receptor is expressed on macrophages, then I go and learn about macrophages. If the receptor is expressed on neutrophils, then I go and learn about neutrophils. I follow the receptor! Follow your interests and you will always find a way to get answers.

Thank you, Professor Hsi-Hsien Lin, for taking the time to talk with us and share the details of your career journey. We hope your insightful advice helps to inspire the early career scientists who read our blog!