陈路在Joan and Ronald Conaways的指导下在Stowers Institute得到生化和分子生物学博士学位。之后又加入了Steven Artandi在斯坦福大学的实验室，从事博士后工作。期间，先后在Nature, Cell, Molecular Cell, PNAS, JBC等上发表论文。并持有斯坦福大学癌症中心授予的Career Transition Fellowship Award。 陈路毕业于武汉大学，并在中科院生物物理所感染免疫中心唐宏组完成本科论文。
Telomerase RNP, a fascinating noncoding RNA-protein complex that safeguards chromosomal ends, controls the proliferative lifespan of most cells. Telomerase resides only in rare stem/progenitor cells, while is absent in most somas due to transcription silencing of its reverse transcriptase gene TERT. Insufficient telomerase activity limits the ability of stem cells to self-renew, leading to tissue decline in premature aging symptoms and normal aging. Excessive telomerase is selectively acquired by ~90% of cancers, enabling their proliferative immortality. Oncogenic activating mutations in the TERT promoter is the most frequent non-coding mutation in cancer genomes.
To shed light into key steps involved in telomerase biogenesis, I combine genomic editing, enzymology, and unbiased RNA structural probing, and discovered an essential catalytic switch within telomerase RNPs (Chen et al. CELL 2018). The unexpected molecular switch depends on a previously recognized “trafficking factor”, known for tethering noncoding RNAs to lipid-droplet-like Cajal bodies. This finding, together with my other works on telomerase RNA 5’ modification (manuscripts under revision), will provide my independent lab with a list of actionable targets to manipulate telomerase in diseases.
To study telomerase regulation in vivo, I successfully generated a humanized mouse model using CRISPR-Cas9 base editor (xCas9-ABE), in which a single nucleotide change has been knocked into the mouse TERT promoter, mimicking its human counterpart. This novel mouse model is predicted to adopt human-like TERT expression pattern, therefore can potentially serve as an ideal animal model for tissue/stem cell biology and anti-cancer therapeutics.
My PhD studies focused on mRNA transcription and chromatin with Joan and Ronald Conaways in the Stowers Institute for Medical Research. I since joined Steven Artandi’s laboratory in Stanford University as a postdoctoral fellow. I published papers in Nature, Cell, Molecular Cell, PNAS, and JBC, and currently hold a Career Transitioning Fellowship Award granted by Stanford Cancer Institute.