Research

Yeast (S. cerevisiae) cell membrane visualized by some membrane proteins fused with RFP and GFP fluorescent markers. Imposition of light from both of markers results in yellow colour. Author:Masur

Cellular Homeostasis

Our lab studies how cells keep themselves in balance when things go wrong. One focus is on pH (the level of acidity inside a cell) which needs to stay within a narrow range for the cell to function properly. When that balance is disturbed, it can lead to damage, aging, or disease. We use simple organisms like baker’s yeast to explore how cells sense and respond to these changes, helping us uncover basic strategies that cells use to stay healthy over time. Yeast have been used to uncover many fundamental aspects of molecular and cellular biology (e.g., cell cycle, transcription, telomerase, vesicular trafficking, autophagy).  

 

Innovative Teaching Lab Design

We also design innovative, research-based laboratory course materials that immerse students in real scientific discovery. Instead of simply following step-by-step experimental procedures with known outcomes, students investigate open-ended questions. These course-based undergraduate research experiences (CUREs) encourage students to think critically, form hypotheses, and analyze results in the context of ongoing scientific inquiry. In many cases, student-generated data contribute directly to our understanding of important biological processes, allowing them to make meaningful contributions to the broader scientific knowledge base while gaining valuable research experience.

Homeostasis and Aging

Aging is a major driving force behind many of the most common diseases in the United States, including heart disease, cancer, diabetes, and Alzheimer’s disease. Gaining a better understanding of how and why cells age is key to developing new ways to prevent or treat these conditions. Surprisingly, many of the biological pathways that influence aging are shared across species, so many of the same molecular mechanisms that affect aging in human cells also operate in simple organisms like yeast. By studying aging in yeast, we’re uncovering the fundamental processes that drive cellular aging, providing a foundation for understanding aging in human cells.

We’re also developing yeast-based tools to search for new compounds that could slow down or change these aging pathways.

 

 

Rare Diseases

While most research focuses on common diseases, our lab is dedicated to studying rare disorders by modeling disease-linked mutations in yeast cells. Yeast offers a powerful, cost-effective system with advanced genetic tools and high-throughput screening capabilities, enabling rapid and unbiased discovery. Because yeast shares many key biological pathways with humans, we can use CRISPR gene editing to introduce many human disease-associated mutations and then perform targeted experiments to understand how these mutations disrupt cellular function.

Ongoing research projects include:

  • Investigating mTOR variants that control cell growth and metabolism

  • Studying V-ATPase mutations that cause distal tubular renal acidosis

  • Exploring defects in heme biosynthesis that lead to porphyria

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Recent Publications

  • Breen, Anna K, Sarah Thomas, David Beckett, Matthew Agsalud, Graham Gingras, Judd Williams, and Brian M Wasko. (2025) 2025. “An MTOR Inhibitor Discovery System Using Drug-Sensitized Yeast.”. GeroScience. https://doi.org/10.1007/s11357-025-01534-8.
    Publisher's Version

    Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species. However, rapamycin has potential off-target and side effects that warrant the discovery of additional TOR inhibitors. TOR was initially discovered in Saccharomyces cerevisiae (yeast) which contains two TOR paralogs, TOR1 and TOR2. Yeast lacking functional Tor1 are viable but are hypersensitive to growth inhibition by TORC1 inhibitors, which is a property of yeast that can be exploited to identify TOR inhibitors. Additionally, yeast lacking FK506-sensitive proline rotamase (FPR1) or containing a tor1-1 allele (a mutation in the Fpr1-rapamycin binding domain of Tor1) are robustly and selectively resistant to rapamycin and analogs that allosterically inhibit TOR activity via an FPR1-dependent mechanism. To facilitate the identification of TOR inhibitors, we generated a panel of yeast strains with mutations in TOR pathway genes combined with the removal of 12 additional genes involved in drug efflux. This creates a drug-sensitive strain background that can sensitively and effectively identify TOR inhibitors. In a wild-type yeast strain background, 25 µM of Torin1 and 100 µM of GSK2126458 (omipalisib) are necessary to observe TOR1-dependent growth inhibition by these known TOR inhibitors. In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identify TOR1-dependent growth inhibition in the drug-sensitized background. This represents a 200-fold and 250-fold increase in detection sensitivity for Torin1 and GSK2126458, respectively. Additionally, for the TOR inhibitor AZD8055, the drug-sensitive system resolves that the compound results in TOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wild-type yeast strain background. Our platform also identifies the caffeine analog aminophylline as a TOR1-dependent growth inhibitor via selective tor1 growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine and found no evidence for TOR inhibition using our yeast growth-based model. Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR pathway. It offers a rapid, cost-efficient, and sensitive tool for drug discovery, with the potential to expedite the identification of new TOR inhibitors that could serve as geroprotective and/or anti-cancer agents.