Allan

Professor

Email: doug.allan@ubc.ca
Phone: 778-235-3555
Website: http://www.douglasallanlab.weebly.com

Postdoc: Harvard Medical School (2000-2005)
PhD: University of Alberta (1994-2000)
MSc: Aberdeen University, Scotland (1992-93)
BSc (Hon): Aberdeen University (1988-1992)



Member, Cell & Developmental Biology Research Group (Life Sciences Institute)
Full Member, Djavad Mowafaghian Centre for Brain Health

Research Interests
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Complex nervous system function depends upon the generation of many different subtypes of neurons during development, and then lifelong modulation of synaptic function by trans-synaptic communication. We study the transcriptional mechanisms controlling gene expression programs that establish neuronal identity and modulate synaptic function in response to retrograde signals form the synapse. Ongoing projects explore how retrograde BMP signaling from the neuromuscular junction intersects with intrinsic transcription factors in motor neurons to direct synaptic growth and homeostasis. Disruption of transcription factors has been linked to congenital neurological disorders, and disruption of intercellular communication and trafficking of target-derived signals has been implicated in neurodegenerative disorders. Our studies provide a mechanistic understanding of how these factors control gene expression pertinent to neuronal function, advancing our understanding of the aetiology of neurological disorders.


Next-generation sequencing has made genetic variant discovery routine clinical practice. However, interpreting the functional consequence of identified variants is challenging. Drosophila offers advantages for scalable clinical variant interpretation. While different on a gross anatomical level, human and Drosophila organ systems and molecular pathways are conserved. Drosophila offers detailed information on genetic and protein interactions for thousands of genes, as well as a versatile and cost-effective suite of molecular genetic tools that makes gene variant analysis highly tractable. Ongoing projects are developingDrosophila assays to interpret the pathogenicity of gene variants for numerous human diseases

Selected Publications
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  1. Vuilleumier R, Miao M, Giro SM, Flibotte S, Lian T, Collins A, Ly S, Pyrowolakis G, Haghighi P, Allan DW. (2022) Dichotomous regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling. Nucleic Acids Research. 50 (17), 9748-9764 
  2. Cyrus SS, Medina Giró S, Lian T, Allan DW*, Gibson WT* (2024) Mimicking Human EED Variants in Drosophila: A Promising Strategy to Analyse Human EED Variant Function. BioRXiv. 2024.02. 18.580839
  3. Ganguly P, Madonsela L, Chao JT, Loewen CJR, O’Connor TP, Verheyen EM, Allan DW (2021)  A scalable Drosophila assay for clinical interpretation of human PTEN variants in suppression of PI3K/AKT induced cellular proliferation PLoS Genetics. 17:9, e1009774
  4. Post KL, Belmadani M, Ganguly P, Meili F, Dingwall R, McDiarmid TA, Meyers WM, Herrington C, Young BP, Callaghan DB, Rogic S, Edwards M, Niciforovic A, Cau A, Rankin CH, O’Connor TP, Bamji SX, Loewen CJR, Allan DW, Pavlidis P, Haas K (2020)  Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction Nature communications 11 (1), 1-16
  5. Berndt AJE, Othonos KM, Lian T, Flibotte S, Miao M, Bhuiyan SA, Cho RY, Fong JS, Hur SA, Pavlidis P, Allan DW (2020) A low affinity cis-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons Elife 9, e59650
  6. Vuilleumier R, Lian T, Flibotte S, Khan ZN, Fuchs A, Pyrowolakis G, Allan DW (2019) Retrograde BMP signaling activates neuronal gene expression through widespread deployment of a conserved BMP-responsive cis-regulatory activation element Nucleic acids research 47 (2), 679-699
  7. Garner SRC, Castellanos MC, Baillie KE, Lian T, Allan DW (2018) Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by a double-assurance survival role for Transformer in females Development 145 (1), dev150821
  8. Berndt AJE, Tang JCY, Ridyard MS, Lian T, Keatings K, Allan DW (2015) Gene Regulatory Mechanisms Underlying the Spatial and Temporal Regulation of Target-Dependent Gene Expression in Drosophila Neurons PLoS genetics 11 (12), e1005754
  9. Allan DW and Thor S (2015) Transcriptional Selectors, Masters and Combinatorial Codes: Regulatory Principles of Neural Subtype Specification. WIREs Developmental Biology. Wiley Interdiscip Rev Dev Biol. 2015 Apr 8.

Further publications can be found here.