Research
Immunotherapy mechanisms and heterogeneity of response
In my work at the Parker Institute for Cancer Immunotherapy (PICI), I analyzed tumor genomic data, imaging data, and flow/mass cytometry data from patient samples in early phase immuno-oncology trials. I was the lead data scientist on the PORTER trial, a phase I platform trial testing novel immunotherapy combinations in metastatic castration-resistant prostate cancer. At the SITC 2022 meeting, I presented posters detailing the pharmacodynamic responses associated with each drug combination, as well as an exploratory analysis of biomarkers correlated with response in patients receiving FLT3L + nivolumab combination therapy.
During my time at PICI, I also led bioinformatics collaborations with NanoString, Inc., using data from their gene expression platform to identify biological processes associated with immunotherapy response in melanoma and lung cancer, and testing the performance of their GeoMx spatial transcriptomics platform across multiple PICI-affiliated research institutions.
Evolution of development and gene regulation
In my academic work, I studied the genetic basis of morphological evolution in the threespine stickleback (Gasterosteus aculeatus), a fish that has undergone large changes in morphology during transitions from marine to freshwater environments. I used genetic crosses to identify genome regions associated with quantitative traits in sticklebacks, and I identified a particular mutation that evolved in freshwater fish and affects the splicing of a skeletal transcription factor, reducing the length of stickleback spines (Howes, Summers, and Kingsley 2017). I also was part of the team that sequenced multiple stickleback genomes to identify regions that differ sharply between marine and freshwater environments. I used high-throughput gene expression data to characterize the types of genes showing differences in the most divergent genomic regions (Jones et al. 2012).
Another QTL that I had identified in my crosses was associated with the number of dorsal spines on a stickleback. Subsequent work by graduate student Julia Wucherpfennig showed that this locus contains the stickleback HOXDB cluster, providing evidence that changes in Hox gene expression can be the basis for naturally occurring morphological evolution in vertebrates (Wucherpfennig et al. 2022). (See also the commentary piece “Sticklebacks and Hopeless Monsters”).