At the Interface of RNA Biology & Genomics: Q&A With Lan Lin, PhD

Editor’s Note: Welcome to our monthly Faculty Spotlight series, in which we sit down with faculty members at Children’s Hospital of Philadelphia Research Institute to learn more about their research and roles. Through these spotlights, our readers meet the diverse, dedicated, and distinctive individuals who lead our research community in our mission to improve children’s health. This year, we will be asking our featured scientists about mentorship — why it matters and how it has influenced their careers. In this Q&A, we feature Lan Lin, PhD, scientist in the Department of Pathology and Laboratory Medicine and the Lin Laboratory. Stay tuned for more from our Faculty Spotlight series throughout this year!

Lan Lin, PhD

How long have you been at CHOP, and can you tell us a little about your research specialty? 

I started my appointment as an assistant professor in the Department of Pathology and Laboratory Medicine at CHOP and the University of Pennsylvania in July 2018. I am also a member of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics (CCMT) at CHOP.

My lab works at the interface of genomics and RNA biology. In particular, we are interested in understanding how messenger RNA (mRNA) processing and modifications impact gene function and cellular phenotypes.

In human cells, after a gene is transcribed from its genomic locus, the nascent RNA can be processed and modified in a variety of ways to generate distinct mRNA and protein products from a single gene. This type of RNA-level regulation is extremely complex, plays important roles in diverse biological processes, and is frequently disrupted in human diseases such as neurological disease and cancer.

My lab develops high-throughput genomic technologies to portray the global patterns of RNA processing and modifications. We also apply these technologies in conjunction with bioinformatics and molecular biology tools to study RNA regulatory mechanisms, as well as the functional impacts of RNA variation in human cells.

Why did you choose to focus on that specialty?

My doctoral work was focused on the function of a single gene in regulating cellular iron metabolism. When I started my postdoctoral training, I was interested in learning global approaches for studying gene regulation and cellular processes. I led several projects to examine the RNA repertoire of mammalian tissues and to explore how novel RNA processing patterns and their resulting gene products emerged during primate and human evolution. Through these studies, I became fascinated by the complexity of RNA, as well as the power of massively parallel sequencing technologies for studying RNA variation.

Tell us about a current or recent research project (or projects) that you are excited about?

My lab is currently supported by a five-year National Institutes of Health (NIH) grant to study chemical base modifications of RNA in human tissues and populations. From this NIH project, as well as other related projects, we are developing several exciting new technologies for studying RNA variation at the global scale (across all RNA molecules expressed in a given tissue or cell type) and at the single-base resolution.

For example, a postdoctoral fellow in the lab who is a microfluidics expert is working on a new microfluidics-based platform for studying RNA modifications in single cells. While these new technologies are going to have broad utilities for basic RNA biology research, we are equally enthusiastic about the potential applications of these technologies in translational and clinical settings.

What are the long-term research questions you hope to answer?

Defects in RNA regulation cause many diseases in children, including rare genetic diseases and cancer. Being at CHOP, I would really love to see our work with RNA technologies be translated into RNA-based diagnostics and therapeutics for children. To this end, we have been actively exploring the clinical applications of RNA genomics tools developed in our lab in collaboration with our clinical colleagues at CHOP.

We recently received a pilot grant from CHOP Pathology’s Diagnostic Innovation Fund to develop an RNA-based technology for improving the genetic diagnosis for inborn errors of immunity, which are individually rare, monogenic, and difficult-to-diagnose diseases with high overall prevalence in children. In the long run, I hope our research can lead to novel precision diagnostic and therapeutic strategies for children affected by a wide range of diseases.

How has mentorship influenced your career? Why do you believe mentoring is important in science? 

I have benefited from having generous support of many mentors and senior colleagues throughout my career. When I joined the lab of Tomas Ganz, MD, PhD, at UCLA as a graduate student, I was very interested in hemojuvelin, a then-newly-identified regulator of iron metabolism and associated diseases. In retrospect, this was a risky project for a new graduate student to take on, but Tom was exceptionally supportive. He provided a great intellectual environment for my doctoral work and encouraged me to explore a broad spectrum of molecular and proteomic methods for characterizing unknown protein function.

In the end, this work led to two first-authored publications in Blood as well as a US patent. In my own lab, I have tried to learn from Tom and encourage our trainees to find and pursue their scientific interests. I consider myself fortunate to have trainees coming into the lab with diverse backgrounds and expertise. I believe it is essential to tailor the mentorship towards individual interests and goals and foster a scientific environment that allows trainees to follow their scientific passions.

Learn more about Dr. Lin’s work.