PhD Thesis
The Evolution of Cell and Tissue Identity at the Maternal-Fetal Interface
Supervisor: Günter Wagner
About me
One of the most compelling scientific questions to me is how complex phenotypes originate. I have become convinced that in order to understand a complex phenotype in the present, we have understand how it was assembled over the course of evolution. I’m a PhD student of Günter Wagner from Yale University. The main driving question of my thesis is, how does a complex evolutionary novelty, the uterine decidua, comprised of highly interdependent and themselves novel interacting parts, come to be pieced together over the course of evolution? Over the past few decades, the decidua’s cardinal cell type, the decidual stromal cell, has emerged as a paradigmatic evolutionary novelty for which the mechanistic underpinnings of its origin are known in increasing detail. My contribution to this line of research was the discovery that its cell type identity is linked to the evolution of a progesterone-dependent genetic switch that created a differential ability of uterine fibroblasts to respond to inflammatory signaling (Stadtmauer & Wagner, 2021 https://doi.org/10.1093/biolre/ioab183). Beyond this cell type, the uterine decidua is perhaps the most recently evolved “tissue type” in the human body – a transient, pregnancy-specific transformation of the endometrium comprising a constellation of specialized cells, including resident macrophages (dMΦ) and natural killer (dNK) cells. In collaboration with the lab of Mihaela Pavličev, I am using single-cell RNA sequencing of uteri from stages spanning the reproductive cycles of species in key phylogenetic positions to study the evolution of cell type identity and interactions throughout the origination and subsequent modification of the mammalian fetal-maternal interface. The core intellectual trajectory of my PhD, therefore, has proceeded from the evolutionary understanding of cell type to a higher level of organization – the tissue, and my ongoing research leverages frameworks from multiple disciplines to understand the emergent properties of tissues.