Developmental potential is the ability of a cell to adopt a number of new identities through differentiation and is the requisite driving force that allows a single-cell zygote to give rise to all cell types and tissues of the adult body. My laboratory group seeks to unravel the mysteries of embryogenesis by investigating the molecular mechanisms that impart developmental potential, control tissue lineage segregation, and promote differentiation within embryonic tissues.
More specifically, my research program focuses on improving our fundamental understanding of mammary gland development to provide insight into optimizing dairy/animal production, improve animal and human health, and contribute towards the development of novel treatments for mammary disease and human breast cancer.
Harsh environmental conditions and poor nutrition during pregnancy can have adverse effects on fetal mammary development that result in impaired mammary function later in adulthood. We aim to determine how these external influences affect multipotent tissue lineage formation during embryonic mammary development in livestock species.
The epithelial-mesenchymal transition (EMT) comprises a series of highly coordinated cellular events that convert epithelial cells to newly motile and mesenchymal identities. EMT is an essential process for many tissues involved in organogenesis, including the mammary gland. We aim to better understand the roles EMT plays during early mammary gland development and mammogenesis.
Three-dimensional cell culture models are powerful tools for studying early embryonic and adult organ development. Furthermore, these in vitro models are valuable for performing genetic manipulations that are difficult to perform in livestock species. We are developing both human and livestock specie mammary organoid systems that recapitulate mammary developmental stages, architecture, function, and cell lineage composition.
This program builds on my past research interests and experiences. Throughout my scientific career, my primary research focus has been to understand how various tissue lineages arise during embryogenesis. My dissertation research aimed to understand how transcription factors regulate segregation of the inner cell mass (embryo) and trophectoderm (extra-embryonic pre-placental) lineages in the pre-implantation blastocyst [MRD, 2013; MRD 2006; Stem Cells 2008; IVCDBA 2012]. As a postdoctoral research fellow, I identified post-translational mechanisms involving cadherins that promoted multipotent neural crest cells to undergo EMT and acquire a mesenchymal identity [PMBTS 2013; MBOC 2104; JCB 2016; Genesis 2017; DB 2018]. Our group at the NIH NIDCR, where I held the position of Staff Scientist, sought to understand how multipotency and stemness are maintained in the premigratory neural crest stem cell niche [NIDCR NCDDU]. Consequently, over the last fifteen years, I have developed a specialized skill set of molecular, biochemical, embryological, and cell culture techniques that I can use to explore the cellular and molecular mechanisms involved in mammary development.