In-Vitro Animal Models
The natural world offers an immense diversity of species, but only a select few can be maintained as laboratory animals. 3D organoids enable the exploration of this diversity while reducing the use of laboratory animals. Multi-species organoids represent the next generation of animal models, making them widely available to the scientific community as a tool for diverse research fields, from drug discovery and infectious diseases to evolutionary biology.
We pioneered the generation of 3D mammary orgnaoids from a variety of mammals. These organoids develop from viable tissues and cells that are stored frozen for long periods, minimizing the need for consistent animal resources.
A central part of my lab’s work under this initiative is the establishment of a bio-bank of cryopreserved, viable mammary gland tissue and organoids from a diverse array of mammals. Our collection currently includes 14 species and sub-species and continues to grow.
Breast Cancer
The origin of breast cancer: Despite decades of breast cancer research, we still have only a very partial understanding of the earliest events and conditions that lead to breast cancer, and of the identity of its cell of origin.
Modelling ductal carcinoma in-situ: Although most DCIS cases do not progress to invasive breast cancer, predicting which lesions will become invasive remains challenging. Consequently, surgical overtreatment is common. Genetic studies show similarities between DCIS and invasive breast cancer cells, suggesting the microenvironment is critical in determining the invasive potential of DCIS. We are developing an organoid model for DCIS that recapitulates its unique intra-ductal anatomy.
Natural resistance to mammary cancer: Remarkably, some species are long known to be resistant to mammary cancer, including the cows, pigs and goats, among others. This phenomenon remains without a mechanistic explanation, despite the its potential to shed light on the origin and causes of breast cancer. We are exploring natural resistance to mammary cancer through organoids derived from resistant and susceptible species.
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Evolution of the Mammary Gland
The evolution of the mammary gland signifies the beginning of the diverse mammalian lineage, categorized into three groups: monotremes, marsupials, and eutherians. Monotremes are ancient egg-laying mammals with specialized hairs secreting milk. Marsupials possess unique mammary glands associated with hair follicles, reflecting the gland's apocrine evolutionary origin. Eutherians, the most expansive mammalian group, have adapted to almost every environment, displaying vast mammary gland variations due to genetic, epigenetic, cellular, and tissue-level differences.
Our mechanistic understanding of these variations remains limited. Delving into this topic holds promise for advancements in areas crucial to human health, such as cancer research, regenerative medicine, and ecological developmental biology.
We generated the first mammary organoid from a marsupial - the gray short-tailed opossum, and are looking to expand this endeavor to monotremes in the near future.
Lactation and Nutrition
Milk composition varies greatly between mammals, and the mechanisms controlling it are not well understood at the tissue level. We aim to explore the regulation of milk secretion and composition in organoids derived from a variety of mammals.
Breast developmental deficiencies can result in adverse health consequences, including failure to breastfeed. We use organoids to gain a better understanding of the developmental events leading to sufficient and adequate breast tissue formation during puberty and later in pregnancy and lactation. These studies will inform prevention and treatment for persons with non-malignant breast pathologies that result from deficient breast development.
Tissue Regeneration
Using live imaging to monitor organoid development from single cells provides a real-time window into tissue regeneration. This method illuminates the orchestrated sequences and directives individual cells follow to create functional tissues and organs, leading to a deeper understanding of mechanisms of tissue growth and organization.
