Andrew Simmonds

 

Not currently recruiting graduate students

Research Interests

Regulation of cell division and differentiation by Vestigial-like proteins

Our research group uses a combination of live-cell imaging, Drosophila genetics, cell-culture and molecular biology to study the regulation of critical cellular processes like peroxisome function, mitosis and cell differentiation.

Understanding the cellular mechanisms underlying peroxisome disorders using Drosophila.

We study two cellular organelles, "lipid droplets" that store fat molecules and "peroxisomes", chemical factories that break down fat molecules so cells can use them for energy. Besides fat storage and processing, lipid droplets and peroxisomes perform other critical roles, especially in the highly specialized cells that make up our organs. At least one child in 40 000 is born with defects in peroxisome genes, causing abnormal development of the brain, eyes, kidneys, and liver. Defects in lipid droplet genes can cause a similar spectrum of diseases. Both types of diseases can put major burdens on the affected patients, their families, and the health care system.

We use the fruit fly, as a simple animal model to study the basic processes that also occur in human cells and organs. For example, we previously used flies to discover new ways that peroxisomes function in human immune cells responding to microbial infection. We are currently characterizing cellular factors that coordinate lipid droplet storage and release of fat molecules and direct these fat molecules to peroxisomes. We will study isolated fly cells as well as cells within the organs of developing flies.

Regulation of myocyte division and differentiation by Vestigial-like proteins

Our lab studies the Drosophila Vesigial proteins, a member of the conserved Vestigail-like family found in most higher metazoans. The Vestigal-like proteins interact with two DNA binding proteins (Scalloped and Myocyte Enhancing Factor-2) that have critical roles in establishing muscle cell fate. Vestigial-like proteins come in two types, oncogenic and tumour-suppressive. Both bind to Scalloped, which is directly regulated by the Hippo cell proliferation/differentiation pathway. There are multiple members of the human Scalloped and Myocyte Enhancing Factor-2 protein families and it has been extremely difficult to identify co-factors that regulate their activity. However in Drosophila melanogaster, there is only a single Scalloped and Myocyte Enhancing Factor-2

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Recent Research

(The names of Simmonds lab members are underlined)

He K, Dee M and Simmonds AJ.Requirements for lipids for brain development and function: what we can learn from Drosophila. Genome 2026  (Invited Review - CanFLY special edition)

He K and Simmonds AJ. Gut Check: Peroxisomes as a Missing Link in Long COVID Intestinal Repair. Developmental Cell. 2026 61(3):466-67 (Invited Preview)

Chang A and Simmonds AJ. Peroxisome inter-organelle cooperation in Drosophila. Genome. 2025 Jan 1:68:1-12. doi: 10.1139/gen-2024-0082 (Invited Review - CanFLY special edition)

Keegan SE, Haskins, J, Simmonds AJ, Hughes SC. A chromatin remodeling SWI/SNF subunit Snr1 regulates neural stem cell determination and differentiation. Development. 2024 150(13): 201484

Ueda K, Haskins J, Simmonds AJ. Manipulation and visualization of peroxisomes in Drosophila. Methods in Molecular Biology. 2023 2643:455-467

Ueda K, Anderson-Baron MN, Haskins J, Hughes SC, Simmonds AJ. Recruitment of Peroxin 14 to lipid droplets affects lipid storage in Drosophila. Journal of Cell Science. 2022 Apr 1;135(7):jcs259092 

Nath AS, Parsons BD, Makdissi S, Chilvers RL, Mu Y, Weaver CM, Euodia I, Fitze KA, Long J, Scur M, Mackenzie DP, Makrigiannis AP, Pichaud N, Boudreau LH, Simmonds AJ, Webber CA, Derfalvi B, Hammon Y, Rachubinski RA, di Cara F. Modulation of the cell membrane lipid milieu by peroxisomal β-oxidation induces Rho1 signaling to trigger inflammatory responses. Cell Reports. 2022 Mar 1;38(9):110433

Liu Y, Weaver CM, Sen Y, Eitzen G, Simmonds AJ, Linchieh L, Lurette O, Hebert-Chatelain E, Rachubinski RA, di Cara F. The nitric oxide donor, S-Nitrosoglutathione, rescues peroxisome number and activity defects in PEX1G843D mild Zellweger syndrome fibroblasts. Frontiers in Cell and Developmental Biology . 2021 Aug 9;9:714710 

Merritt TJS, Simmonds AJ, Fernandez-Gonzalez R, Moehring AJ. Introduction: CANFLY XV 2019. Genome. 2021 Feb;64(2):vii-viii Conference Report

Pridie C, Simmonds AJ. The role of Peroxin 7 during Drosophila embryonic development. Genome. 2021 Feb;64(2):119-137

Pridie C, Ueda K, Simmonds AJ. Rosy Beginnings: Studying peroxisomes in Drosophila. Frontiers in Cell and Developmental Biology. 2020 Aug 25;8:835. Invited Review

Huang K, Miao T, Chang K, Kim J, Kang P, Jiang Q, Simmonds AJ, di Cara F, Bai H. Impaired peroxisomal import in Drosophila oenocytes causes cardiac dysfunction by inducing upd3 as a peroxikine. Nature Communications. 2020 Jun 10;11(1):2943 

Hughes SC, Simmonds AJ. Drosophila mRNA localization during later development: past, present, and future. Frontiers in Genetics. 2019 Mar 7;10:135. Invited Review

 

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Laboratory Members

Graduate Student
Andy Cheng
James Stewart
Karen He

Technicians
Julie Haskins
Maddie Dee
Kyle Kohls-Wiebe