Eric Lai




Small RNAs in Drosophila
Recent years have seen phenomenal advances in our understanding of regulatory pathways mediated by small RNA/Argonaute complexes. We seek to define the small regulatory RNAs of Drosophila using high throughput sequencing and bioinformatics, and to probe their biogenesis and function using biochemical and genetic strategies. In the past year, these efforts yielded not only additional members of the conventional microRNA gene class, but also revealed several novel aspects of microRNA biogenesis along with a plethora of endogenous siRNA-generating loci. We and others have also found that many of these small RNA-generating mechanisms are conserved in mammals. The existence of these new pathways increases the complexity of the small RNA-mediated regulatory network, raises new questions about the segregation and sorting of RNA substrates through these various pathways, and may potentially lend insight into improving the exploitation of regulatory RNAs for designed or therapeutic purposes.




2005 - Present
Assistant Member, Department of Developmental Biology
Memorial Sloan-Kettering Cancer Center
Assistant Professor, Program in Cell Biology and Genetics
Weill Cornell Medical School

BS Biochemistry - Harvard University
PhD Biology - UCSD

Research Interests
Control of developmental patterning in Drosophila by Notch signaling and microRNAs
As a laboratory of developmental biology, our guiding interest is to comprehend how complex biological patterns can be assembled with stereotyped precision. This requires a detailed understanding of how cells come to execute appropriate behaviors -- be it adoption of specific cell fates, proliferation, or apoptosis -- and do so at the right times, in the right places, and in the right numbers. Dysfunction of processes that direct normal tissue patterning results not only in developmental disorder but also underlies adult disease. Tellingly, many factors whose mutation is relevant to human cancer were first identified and characterized with respect to development in model organisms.

We choose the fruitfly Drosophila melanogaster as our principal model system, based on its wealth of sophisticated genetic tools and depth of comparative genomic data. We study two topics in developmental patterning: (1) determination of cell fates by a cell-cell signaling cascade known as the Notch pathway and (2) the biological activities of microRNAs, a newly defined class of endogenous small regulatory RNAs. We study these with respect to the development of several fly tissues that are intricately yet robustly patterned. For example, the body surface of the fly is covered with mechanosensory bristles, which constitute most of its peripheral nervous system (Figure 1). The pattern of bristles is very stable in wildtype flies but is readily amenable to genetic manipulation.

By studying how bristle patterning and other developmental events are altered by manipulating Notch signaling and microRNA function, we hope to better understand how these molecular systems organize pattern elements. Conversely, we can use these developmental paradigms in forward genetic screens to isolate novel genes that control developmental patterning.

For more information about Eric, visit his web page at Sloan-Kettering Institute:



Return to Top