On Wednesday afternoon, Haifan Lin, the director of the Yale Stem Cell Center, discussed his innovative research findings in stem cell gene expression and regulation at Brown’s 2025 Mac V. Edds Lectureship.
Hosted by the Department of Molecular Biology, Cell Biology and Biochemistry, the event is held on a near-annual basis to honor Edds’s legacy. A pioneer in the field of developmental biology, Edds was the former director of medicine in Brown’s Division of Biology and Medicine.
Lin opened his lecture by discussing the shortcomings in the conventional understanding of gene expression and regulation, which is explained through the central dogma of biology that refers to the genetic flow of information from DNA to RNA and then protein.
Genetic regulation is controlled through a variety of mechanisms in this pathway, including changes at the transcriptional level — or the process of producing messenger RNA from DNA. These changes encompass processes like epigenetic regulation, which alters gene expression by chemically modifying DNA without changing the underlying DNA sequence, Lin said.
He explained that historically, stem cell research has focused on transcription factors, and as a result, far less is known about the role of post-transcriptional regulation. Lin acknowledged the dearth of research on gene expression of embryonic stem cells — cells found in the early stages of embryonic development and capable of differentiating into most cell types in the adult body — and discussed how his own research addressed these gaps.
In one study, Lin explored the role of pumilio proteins in post-transcriptional control. Pumilio proteins are a family of proteins that bind to RNA to control protein production after transcription in early embryogenesis.
Lin helped discover that Pum1 proteins — a subset of pumilio proteins — play a crucial role in the differentiation of stem cells, while Pum2 proteins promote properties that allow stem cells to replicate themselves. Through regulating over a thousand types of mRNAs, these proteins can enhance or repress protein synthesis.
In the second half of the talk, Lin discussed his discovery of a novel group of small noncoding RNA molecules called PIWI-interacting RNAs, or piRNAs. The journal Science included Lin’s discovery in their list of 2006’s 10 most important scientific breakthroughs.
Lin’s studies found that piRNAs derived from certain DNA segments are capable of degrading mRNA and other non-coding forms of RNA.
“We were euphoric about these findings,” Lin said during the lecture. “If you liken the genome to the world, the traditional genes are like the old world, and suddenly, we found ourselves landed in a completely new world.”
Jien Li GS, a second-year graduate student studying aging biology, shared his surprise at the novelty of these findings and the existing limitations in the field.
“It shows how much more there is to discover,” Li said. These findings, he added, “are important enough that we should have a better understanding of (them) by now, but we don’t.”
Jonathan Kim is a senior staff writer covering Science and Research. He is a second-year student from Culver City, California planning to study Public Health or Health and Human Biology. In his free time, you can find him going for a run, working on the NYT crossword or following the Dodgers.