Alan Underhill, PhD

Area of Study / Keywords

Epigenetics Breast cancer Paediatric cancer Neurodevelopmental disorders Chromatin biology Histone modifications

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About

Dr. Alan Underhill is currently appointed as Associate Professor in the Department of Oncology in the Faculty of Medicine & Dentistry.

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Research

The Underhill laboratory is interested in deciphering how histone modifications regulate genome structure and function, and their alteration in disease.

Epigenetic control in development and cancer

An essential component in the management and functional output of eukaryotic genomes is that their DNA is assembled into chromatin via the formation of nucleosomes, which comprise 147 bp of DNA wrapped nearly twice around an octamer of the core histone proteins H2A, H2B, H3, and H4 in equal stoichiometry. In addition to providing a means to compact the genome so that it fits within the confines of the nucleus, chromatin serves diverse roles in facilitating expression, repression, replication, recombination, repair of damaged DNA, mechanical stability, and mitosis. Over and above the regulatory information embedded in the genome, these different processes require a broad range of epigenetic controls that include chemical modification of DNA and histones, histone variants, linker histones, and other chromatin architectural proteins. Within this scheme, our laboratory is examining how the methylation of lysine 20 on histone H4 modulates multiple facets of chromatin structure and function.  We have a particular interest in how defects in this pathway contribute to disease progression in breast cancer and pediatric glioma, as well as its dysfunction in neurodevelopmental disorders.

We make extensive use of genetic, molecular, biochemical, and state-of-the art cell-imaging approaches for our research, which is supported by grants from the Cancer Research Society, Canadian Institutes of Health Research, Women and Children’s Hospital Research Institute, and Brain Tumour Foundation of Canada.

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Teaching

ONCOL 520, ONCOL 425/525, ONCOL 620

Strickfaden H, Abate N, Förster C, Wuest F, Underhill DA, Hendzel MJ

Microscopy (Oxford, England). 2023 August; 10.1093/jmicro/dfad022

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Roemer A., Mohammed L., Strickfaden H., Underhill D.A., Hendzel M.J.

Frontiers in Genetics. 2022 August; 13 10.3389/fgene.2022.876862

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Strickfaden H, Missiaen K, Knechtel JW, Hendzel MJ, and Underhill DA

bioRxiv preprint. 2021 November; 10.1101/2021.11.04.467369

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Githaka J.M., Tripathi N., Kirschenman R., Patel N., Pandya V., Kramer D.A., Montpetit R., Zhu L.F., Sonenberg N., Fahlman R.P., Danial N.N., Underhill D.A., Goping I.S.

Nature Communications. 2021 May; 12 (1) 10.1038/s41467-021-23269-8

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Strickfaden H., Tolsma T.O., Sharma A., Underhill D.A., Hansen J.C., Hendzel M.J.

CELL. 2020 December; 183 (7):1772-1784.e13 10.1016/j.cell.2020.11.027

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