I received a B.S. in Physics with a minor in Biological Sciences at Stanford. As an undergraduate researcher, I worked in the labs of Profs. Dan Herschlag, Upinder Singh, and Steven Block. I then did my Ph.D. research in Biophysics at UC Berkeley with Prof. Daniel Fletcher, studying how mechanical forces affect branch nucleation in actin networks. During graduate school, I also attended the Woods Hole Marine Biology Lab Physiology Course and designed and taught a course on quantitative image analysis for biologists. I am currently a postdoctoral scholar in the lab of Prof. William Greenleaf, where I study chromatin structure at multiple length scale using existing and novel epigenomic assays.
Bachelor of Science, Stanford University, PHYS-BSH (2004)
Bachelor of Science, Stanford University, BIOL-MIN (2004)
William Greenleaf, Postdoctoral Faculty Sponsor
Variable chromatin structure revealed by in situ spatially correlated DNA cleavage mapping.
2017; 541 (7636): 237-241
Chromatin structure at the length scale encompassing local nucleosome-nucleosome interactions is thought to play a crucial role in regulating transcription and access to DNA. However, this secondary structure of chromatin remains poorly understood compared with the primary structure of single nucleosomes or the tertiary structure of long-range looping interactions. Here we report the first genome-wide map of chromatin conformation in human cells at the 1-3 nucleosome (50-500 bp) scale, obtained using ionizing radiation-induced spatially correlated cleavage of DNA with sequencing (RICC-seq) to identify DNA-DNA contacts that are spatially proximal. Unbiased analysis of RICC-seq signal reveals regional enrichment of DNA fragments characteristic of alternating rather than adjacent nucleosome interactions in tri-nucleosome units, particularly in H3K9me3-marked heterochromatin. We infer differences in the likelihood of nucleosome-nucleosome contacts among open chromatin, H3K27me3-marked, and H3K9me3-marked repressed chromatin regions. After calibrating RICC-seq signal to three-dimensional distances, we show that compact two-start helical fibre structures with stacked alternating nucleosomes are consistent with RICC-seq fragmentation patterns from H3K9me3-marked chromatin, while non-compact structures and solenoid structures are consistent with open chromatin. Our data support a model of chromatin architecture in intact interphase nuclei consistent with variable longitudinal compaction of two-start helical fibres.
View details for DOI 10.1038/nature20781
View details for PubMedID 28024297
Unraveling the 3D genome: genomics tools for multiscale exploration.
Trends in genetics
2015; 31 (7): 357-372
A decade of rapid method development has begun to yield exciting insights into the 3D architecture of the metazoan genome and the roles it may play in regulating transcription. Here we review core methods and new tools in the modern genomicist's toolbox at three length scales, ranging from single base pairs to megabase-scale chromosomal domains, and discuss the emerging picture of the 3D genome that these tools have revealed. Blind spots remain, especially at intermediate length scales spanning a few nucleosomes, but thanks in part to new technologies that permit targeted alteration of chromatin states and time-resolved studies, the next decade holds great promise for hypothesis-driven research into the mechanisms that drive genome architecture and transcriptional regulation.
View details for DOI 10.1016/j.tig.2015.03.010
View details for PubMedID 25887733
View details for PubMedCentralID PMC4490074
A conditional system to specifically link disruption of protein-coding function with reporter expression in mice.
2014; 7 (6): 2078-2086
Conditional gene deletion in mice has contributed immensely to our understanding of many biological and biomedical processes. Despite an increasing awareness of nonprotein-coding functional elements within protein-coding transcripts, current gene-targeting approaches typically involve simultaneous ablation of noncoding elements within targeted protein-coding genes. The potential for protein-coding genes to have additional noncoding functions necessitates the development of novel genetic tools capable of precisely interrogating individual functional elements. We present a strategy that couples Cre/loxP-mediated conditional gene disruption with faithful GFP reporter expression in mice in which Cre-mediated stable inversion of a splice acceptor-GFP-splice donor cassette concurrently disrupts protein production and creates a GFP fusion product. Importantly, cassette inversion maintains physiologic transcript structure, thereby ensuring proper microRNA-mediated regulation of the GFP reporter, as well as maintaining expression of nonprotein-coding elements. To test this potentially generalizable strategy, we generated and analyzed mice with this conditional knockin reporter targeted to the Hmga2 locus.
View details for DOI 10.1016/j.celrep.2014.05.031
View details for PubMedID 24931605
View details for PubMedCentralID PMC4113058