Dr. Safia Omer

My research career began with a fascination for molecular biology and genetics during my undergraduate studies at the University of Khartoum. Being centered in Sudan, a region significantly affected by tropical diseases, I examined genetic factors of pathogens like Plasmodium and Leishmania that interact with and evade host systems. Crossing the Saharan Desert and the Atlantic to the University of Massachusetts, US, I pursued my PhD in the laboratory of Dr. Wei-Lih Lee where I learned cell biology and advanced microscopy and applied them to study the regulation of the dynein motor complex, an ancient and essential molecular machine that drives intracellular transport and cell division. My work focused on elucidating how the cortical anchor protein Num1 localizes dynein to specific sites on the cell membrane to generate precise pulling forces on microtubules in budding yeast, a powerful model organism.

Eager to translate my expertise in cytoskeletal mechanics into disease-relevant mammalian systems, I moved to the University of Toronto Scarborough for my postdoctoral research in the laboratory of Dr. Rene Harrison. My research examined the critical role of the cytoskeleton in macrophage-mediated innate immunity. This work revealed how the centrosomal protein ninein orchestrates F-actin remodeling and dynein-driven phagosome movement, a process that is critical for efficient phagocytosis. This finding provided a crucial link between cytoskeletal regulators and immune cell function, demonstrating how basic cellular machinery is co-opted for host defense. At the University of Guelph, my research program starting 2025 focusing on elucidating how cytoskeletal networks and their regulators contribute to the mechanisms of immune response and human disease.

• Post-doctoral fellow, SickKids Hospital
• Post-doctoral fellow, University of Toronto
• Ph.D. in Molecular and Cellular Biology, University of Massachusetts, Amherst, US
• M.Sc. in Molecular Medicine, Institute of Endemic Diseases, Sudan
• B.Sc. (Hons) Zoology, University of Khartoum, Sudan

"Think of a cell as a busy city. It needs a transportation system to move cargo. This system is built from two main parts: the roads and the trucks. Microtubules are the long, sturdy protein filaments that form the roads, while specialized motor complexes are the molecular machines that act as the trucks".

The lab is dedicated to gaining a mechanistic understanding of how the cellular transport system is regulated. We focus on the cell's most powerful motor: dynein that traffic cargo inward to the cell center. The activity of dynein is not self-directed; it is coordinated by a large suite of adaptor proteins. These adaptors play a critical role in localizing the motor to the specific cargo at the right time. We use advanced microscopy and biochemical assays to study motors and adaptors in specialized immune cells and non-specialized cells.

The Immune Cell as a Defense Hub

Macrophages, powerful innate immune cells are responsible for ingesting and destroying pathogens, dead cells, and foreign particles through a critical process called phagocytosis. A macrophage can engulf targets as small as viruses, bacteria and as large as other cells, requiring massive, coordinated restructuring of its cytoskeleton and membrane.

Key Research Questions

Our research program is structured around several key questions that bridge fundamental cell biology with immunology and disease:

1. How do dynein and adaptor proteins facilitate the immune response? Phagocytosis is more than just engulfment. Once a particle is internalized into a phagosome, this vesicle must be transported along microtubules to the cell interior for fusion with lysosomes, where degradation occurs. We hypothesize that dynein and specific adaptors are recruited to the nascent phagosome to power this critical journey. Understanding this link is key to explaining how immune cells efficiently destroy invaders.

2. What dictates the efficient engulfment of particles of different sizes? Engulfing a bacterium is different from engulfing an apoptotic cell. We are investigating how the cell scales its response. Specifically, we are studying how the microtubule network and associated motors reorganize to support the pulling for big targets.

3. How do tubulin mutations alter a macrophage's ability to mediate phagocytosis? Mutations in tubulin, the building block of microtubules, are linked to a spectrum of neurodevelopmental disorders. However, their impact on immune function is poorly understood. If the "roads" themselves are structurally compromised, how does this affect the transport of phagosomes?

4. How do tubulin mutations alter the distribution of cellular organelles? The microtubule cytoskeleton is the primary scaffold for organizing the entire cell. A tubulin mutation doesn't just impair transport; it can disrupt the entire cellular landscape. We are using microscopy to map the position of key organelles—including the Golgi apparatus, mitochondria, and lysosomes—in mutant cells. This project is a collaborative effort with the Ivakine Lab at SickKids Hospital.

• Canadian Institutes of Health Research, (CIHR)

• Antonio Mollica, Safia Omer,…, Rene E. Harrison, Ronald D. Cohn, Evgueni A. Ivakine. Mutations in the β-tubulin TUBB impair ciliogenesis and cause ciliopathy-like brain abnormalities in humans and mice. doi: https://doi.org/10.1101/2023.05.23.23290232. A ccepted Nature Communication.

• Safia Omer, Elizabeth Persaud, Safia Mohammad, Bolu Ayo-Farinloye, Rebecca E. Heineman, Emily Wellwood, G. Adam Mott, Rene E. Harrison. Ninein isoform contributions to intracellular processes and macrophage immune function. Journal of Biological Chemistry. 2025, DOI: 10.1016/j.jbc.2025.108419.

• Cara Fiorino, Safia Omer*, Nisha Gandhi, and Rene E. Harrison. In Vitro Assay to Examine Osteoclast Resorptive Activity Under Estrogen Withdrawal. Bio-protocol. 2025, 15(1): e5155. DOI: 10.21769/BioProtoc.5155. *Co-first authorship.

• Safia Omer, Jiahao Li, Claire X. Yang, and Rene E. Harrison. Ninein promotes Factin cup formation and inward phagosome movement during phagocytosis in macrophages. Molecular Biology of the Cell. 2024, 1;35(3):ar26. https://doi.org/10.1091/mbc.E23-06-0216.

• Nisha Gandhi, Safia Omer and Rene E. Harrison. In Vitro Cell Culture Model for Osteoclast Activation during Estrogen Withdrawal. International Journal of Molecular Sciences. 2024, 25(11), 6134. https://doi.org/10.3390/ijms25116134.

• Safia Omer*, Katia Brock, John Beckford, and Wei-Lih Lee. Overexpression of Mdm36 reveals Num1 foci that mediate dynein-dependent microtubule sliding in budding yeast. Journal of Cell Science. 2020, 133 (20): jcs246363. 10.1242/jcs.246363

• Safia Omer, Samuel R Greenberg, and Wei-Lih Lee. Cortical dynein pulling mechanism is regulated by differentially targeted attachment molecule Num1. eLife, 2018, 7:e36745. https://doi.org/10.7554/eLife.36745
• Steven M. Markus, Safia Omer*, Kaitlyn Baranowski, and Wei-Lih Lee. Improved Plasmids for Fluorescent Protein Tagging of Microtubules in Saccharomyces cerevisiae. Traffic. 2015, 16:773–786. DOI: 10.1111/tra.12276. *Co-first authorship.