Science

I’m broadly interested in computational biology, bioinformatics, and the software stack for doing comp bio research at scale. The specific science of what I’ve worked on has varied over the years – here’s a sampling of past research projects.

Loyal: Epigenetics and aging in canines

I currently lead the bioinformatics team at Loyal, where we’re building massive datasets of DNA methylation in dogs. The long term goal of this research is to better understand the aging process, develop drugs that can slow aging in canines, and develop the companion canine as a model for translational aging research.

Stanford PhD Thesis: Transmission of the human microbiome: from infants to infections

My PhD work in the Bhatt Lab at Stanford Genetics centralized around quantifying how humans acquire and transmit bacteria and viruses in the gut microbiome. To do this, I used advanced metagenomic techniques, developed methods for comparing genomes at the precise strain level, and sequenced tons of stool samples!

CMap at The Broad Institute: Genetic and transcriptional instability alters cancer cell line drug response

Cell lines are a workhorse of cancer research, but they’re not always what you expect. We isolated different clones of supposedly identical cell lines and found wide variation in gene mutations, copy number alterations and gene expression levels. These differences were also associated with differential response to anti-cancer drugs. This could explain some of the difficulties reproducing cell line-based research, but the news isn’t all bad — panels of isogenic-like cell lines could be used to predict mechanisms for new cancer drugs. This work was led by Uri Ben-David and published in Nature.
I worked in CMap from 2015-2017. For more info, see this page.

Brown Computational Biology Senior Honors Thesis: A multi-scale ensemble model for chromatin conformation

Methods to infer 3D genome structure from 2D HiC contact matrices  make assumptions about constant processes at all scales. Here, I developed a statistical method to reconstruct an ensemble of 3D structures representing the underlying population of cells.

Neretti Lab at Brown: Chromatin conformation and senescence

How does the 3D organization of the genome change as cells become replicatively senescent? We found a global decrease in long-range 3D contacts, as well as entire chromatin domains that switched from inactive to active compartments (or vice-versa). Contacts measured with Hi-C were validated on a subset of regions with 3D-FISH.

Brown junior year: Tetranucleotide usage in mycobacteriophage genomes

Working with a stellar group of freshman undergraduates in the Phage Hunters course, we developed a method to compare mycobacteriophage genome sequences using the frequencies of 4-letter DNA words (tetranucleotides). This method highlighted some different evolutionary relationships between groups of phage when compared with standard genome alignment.