Kacey Prentice

Affiliations:

• Department of Physiology, University of Toronto
• Banting & Best Diabetes Centre
• Canadian Islet Research Training Network (CIRTN)

Courses Taught: PSL304, PSL425/1425, PSL1066, PSL1070, PSL1034, PSL4010, BCH2139/2140

Research Interests:

Our lab studies mechanisms driving diabetes pathogenesis, with a central focus on pancreatic beta cell dysfunction in both Type 1 and Type 2 Diabetes. We investigate how disrupted communication between insulin-responsive tissues (particularly adipose tissue and liver) alters the circulating environment during the prediabetic state, increasing stress on beta cells and impairing their function. Using a combination of in vivo, ex vivo, and in vitro approaches, we examine the roles of circulating metabolites, hormones, and extracellular vesicles in regulating insulin secretion, cell signaling, and metabolic homeostasis. A key objective of our work is to identify novel therapeutic targets and interventional strategies to preserve beta cell function and delay or prevent the onset of diabetes.

Detailed Description:

Diabetes is a chronic disease that affects hundreds of millions of people worldwide and is fundamentally driven by an insufficient supply of insulin. While Type 1 Diabetes (T1D) is often associated with immune-mediated destruction of insulin-producing pancreatic beta cells and Type 2 Diabetes (T2D) with insulin resistance, both conditions ultimately converge on the inability of beta cells to meet the body’s insulin demands. Increasingly, research shows that this dysfunction begins years before diagnosis, during a prediabetic period when subtle changes in the body place stress on beta cells, contributing to their decline. The primary focus of our lab is understanding how communication between organs, particularly adipose tissue, liver, and pancreas, shapes this early environment and contributes to the development of diabetes.

We use a combination of experimental models, including cell-based systems, isolated human and mouse tissues, and preclinical animal models, to recreate key aspects of diabetes progression. By integrating approaches such as multi-omics, live-cell imaging, molecular biology, biochemistry, and functional assays, we examine how circulating factors such as metabolites, proteins, and extracellular vesicles alter cellular signaling and metabolic pathways in key metabolic tissues, including beta cells.

Our overarching goal is to translate these discoveries into new strategies to preserve beta cell function and delay or prevent the onset of diabetes. By identifying the signals and pathways that drive early dysfunction, we aim to uncover targets for therapeutic intervention that can be modulated before irreversible damage occurs. This includes the development of novel biologics and small molecules designed to restore healthy inter-organ communication and reduce stress on beta cells. Ultimately, our work seeks to shift the treatment paradigm from managing diabetes after it develops to intervening earlier, improving long-term health outcomes and quality of life for individuals at risk.

Research Approach:

• Preclinical and human model systems
  In vivo mouse models of T1D and T2D, ex vivo primary tissues, and human islet/tissue studies
• Cellular and molecular biology
  In vitro cell systems, gene expression, protein analysis, and genetic perturbation (knockdown/knockout/overexpression)
• Functional phenotyping of metabolic tissues
  Insulin secretion assays, live-cell imaging, and cellular stress/function assays
• Metabolic and in vivo phenotyping
  Glucose tolerance tests, insulin sensitivity measurements, and whole-body metabolic assessments
• Omics and circulating factor profiling
  Metabolomics/lipidomics and analysis of circulating signals including metabolites, proteins, and extracellular vesicles
• Biochemical, signaling, and pharmacologic studies
  Pathway analysis, extracellular vesicle characterization, and small molecule/biologic perturbation approaches
• Data integration and systems-level analysis
  Integration of multi-omics and functional datasets to define mechanisms of inter-organ communication

Training Opportunities:

Our lab provides interdisciplinary training in metabolic physiology, molecular biology, and systems-level approaches to disease. Trainees gain experience in experimental design, advanced techniques, and data integration, with opportunities to present at national and international conferences.