For anyone interested in learning more about my research, below are short synopses of my publications.

MD/PhD Publications

1. Oncolytic virus-driven immune remodeling revealed in mouse medulloblastomas at single cell resolution

Jack Hedberg, Adam Studebaker, Luke Smith, Chun-Yu Chen, Jesse J Westfall, Maren Cam, Amy Gross, Ilse Hernandez-Aguirre, Alexia Martin, Doyeon Kim, Ravi Dhital, Yeaseul Kim, Ryan D Roberts, Timothy P Cripe, Elaine R Mardis, Kevin A Cassady, Jeffrey Leonard, Katherine E Miller

Summary: In this initial paper from my PhD, we showed that the oncolytic herpes simplex virus (oHSV) C134, currently under clinical study for adult glioblastoma, exerts a survival benefit in murine models of medulloblastoma, the most common brain malignancy in children. We then used single cell RNA sequencing to define the effect of oncolytic virotherapy on tumor-infiltrating immune cell dynamics across multiple timepoints and medulloblastoma subgroup models, revealing cell type-specific gene signatures of oHSV treatment spanning interferon signaling, cytokine release, and antigen presentation, as well as revealing that oHSV therapy increased the presence of M1-like macrophages. Taken together with the survival benefit demonstrated by C134 and orthogonal flow cytometry data validating single cell sequencing findings, this study advances the understanding of oncolytic virotherapy’s widespread impacts on brain tumor-infiltrating immune cells and highlights C134 as a potential new therapy for medulloblastoma.

Undergraduate Publications

2. Bi-allelic MCM10 variants associated with immune dysfunction and cardiomyopathy cause telomere shortening (Nature Communications)

Ryan M. Baxley, Wendy Leung, Megan M. Schmit, Jacob Peter Matson, Lulu Yin, Marissa K. Oram, Liangjun Wang, John Taylor, Jack Hedberg, Colette B. Rogers, Adam J. Harvey, Debashree Basu, Jenny C. Taylor, Alistair T. Pagnamenta, Helene Dreau, Jude Craft, Elizabeth Ormondroyd, Hugh Watkins, Eric A. Hendrickson, Emily M. Mace, Jordan S. Orange, Hideki Aihara, Grant S. Stewart, Edward Blair, Jeanette Gowen Cook & Anja-Katrin Bielinsky

Summary: This publication emerging from my undergraduate research lab sought to better define the underlying mechanisms responsible for phenotypes of patients with mutations in the DNA replication fork protein MCM10. Here we showed that loss of MCM10 constrains the activity of telomerase, leading to buildup of abnormal replication structures in cells and arrested replication forks that require the activity of MUS81 for viability and telomere integrity. My undergraduate honors thesis project involved using CRISPR/Cas9 to generate an MCM4 heterozygous knockout cell line, which did not show the telomere erosion phenotype observed with MCM10 knockout cells, helping to demonstrate the specificity of this phenotype to MCM10.