Research interests
Understanding how mobile genetic elements spread
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Human LINE-1 retrotransposition​
Nearly half of the genomic content of mammals are mobile genetic elements. The human genome is also dominated by one mobile element, LINE-1 from the retrotransposon family, which copy-and-paste in the genome using an RNA intermediate.
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I employ biochemical, biophysical, structural biology and genetic approaches to unravel how transposon-encoded proteins and nucleic acids enable their spread. My recent publication reveals how the LINE-1 enzyme has created a third of the human genome.
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Vertebrate R2 retrotransposons​
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R2 retrotransposons are site-specific retrotransposons that insert into the ribosomal DNA loci of many eukaryotes. R2 elements from vertebrates are being engineered into safe-harbor genome insertion tools. In our recent work, I have been employing structural biology approaches to unravel how vertebrate R2 retrotransposons insert genes by resolving distinct mechanistic steps during insertion. By combining these approaches with transgene insertion assays in vitro and in cells, we are elucidating the key features that R2 retrotransposon proteins utilize for precise genome insertion in human cells.
Harnessing transposons for biotechnology
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Understanding the molecular mechanisms that transposons use to mobilize will guide efforts to engineer them for new biotechnological applications.
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I am interested in engineering retrotransposons for programmable genome insertion in human cells for gene therapy and future genome engineering efforts.
Mechanisms of microtubule nucleation in the cell
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Microtubule cytoskeleton helps a eukaryotic cell maintain its shape and internal organization. Microtubules also assemble the mitotic spindle, a dense machinery that partitions chromosomes equally into two daughter cells during cell division. During my PhD, I investigated how the microtubule cytoskeleton forms and functions within the mitotic spindle.
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I established bottom-up, biochemical reconstitution methods to visualize individual microtubule nucleation events from the universal microtubule nucleator, the γ-tubulin ring complex (γ-TuRC). Using biophysical and cell biological approaches, I discovered new factors necessary for robust microtubule nucleation and identified their mechanism of action.
