About

I am a cancer biologist trained in epigenomics with the long-term goal of understanding how brain tumours rewire chromatin states targetable by emerging molecular therapies. I am currently a postdoctoral research scientist in the laboratory of Dr. Chao Lu at Columbia University, supported by a ChadTough Defeat DIPG Foundation fellowship and, before that, a fellowship from the Canadian Institutes of Health Research.

I study diffuse midline glioma (DMG), a paediatric brain tumour that carries a dismal prognosis with a median survival under one year. DMG is defined by a mutation in histone H3; H3K27M, an 'oncohistone' that globally reorganises the tumour epigenome. My work has centered on how this mutation impairs differentiation potential of glial lineages from which tumours arise, and how this creates therapeutic opportunities given the unique biology of this disease.

Research

The H3K27M mutation is a dominant-negative inhibitor of Polycomb Repressive Complex 2 (PRC2) capacity to spread H3K27me2/3 histone modifications that establish repressive heterochromatin state. Using CRISPR-edited isogenic patient-derived cell models, our work demonstrated that H3K27M blocks the processive regional spread of each methylation state and is essential for tumor maintenance in vivo (Harutyunyan, Krug et al., Nature Communications, 2019; Harutyunyan et al., Cell Reports, 2020). These models further revealed that elevated H3K27 acetylation (H3K27ac) of DMGs is pervasively deposited across the epigenome, rendering tumor cells vulnerable to the triggering of innate immune viral mimicry upon histone deacetylase inhibitor and DNA demethylating agent treatment (Krug et al., Cancer Cell, 2019).

Beyond the linear epigenome, we examined how H3K27M-driven chromatin dysregulation shapes three-dimensional genome architecture and tumor developmental identity. We showed that confined H3K27me3 domains in H3K27M DMG elevate canonical Polycomb Repressive Complex 1 (cPRC1) loop interactions at target genes, locking tumor cells in an undifferentiated progenitor state (Krug et al., Nature Genetics, 2026). This model is of importance to interpreting a variety of cancer driver events that alter the spreading of H3K27me3, including mutations associated with leukemias and lymphomas. Polycomb-gain-of-function effects present a point of convergence for enhanced self-renewal across multiple brain tumor entities (Krug et al., Trends in Cell Biology, 2021).

Background

I have a longstanding interest in biology that was first sparked by reading Richard Dawkins' The Selfish Gene as a teenager. This led to involvement in research at the University of Guelph where I grew up, and competing at high school international science fairs (Intel ISEF, Sanofi BioTalent). I completed both my PhD in Human Genetics and my BSc in Biology at McGill University in Montreal. Outside the lab I enjoy nordic skiing, cycling and hiking.