Mary C. Mullins, Ph.D.
Professor of Cell and Developmental Biology
Department: Cell and Developmental Biology
1211 BRB II/III
421 Curie Boulevard
Philadelphia, PA 19104-6058
I am interested in studying the pathogenesis and possible treatments for Fibrodysplasia Ossificans Progressive (FOP), a rare genetic disorder characterized by ossification of extra-skeletal sites. FOP is caused by a mutation of ACVR1 that results in over-activation of BMP signaling. In zebrafish BMPs play an important role in dorsoventral patterning. Over-activation of BMP signaling results in perturbation of this patterning. My goal is to determine which of the various BMP type I and type II receptors are involved in the pathogenesis of this disease. In addition, I plan to use zebrafish embryos to screen for compounds that reduce or ameliorate BMP over-activation in FOP. This project will elucidate BMP receptor interactions and aid in the development of targeted therapies for FOP.
James A. Dutko, PhD
My research focuses on the role of Bone Morphogenetic Protein (BMP) signaling in patterning the early vertebrate embryo. I am testing several hypotheses to decipher the mechanism by which BMP heterodimers exclusively signal during dorsoventral patterning and whether BMP heterodimers are used more generally during development. To test these ideas, I am using a combination of biochemical and in vivo assays. During my postdoc, I plan to become proficient in the use of zebrafish as a model organism with the long-term goal of establishing my own lab to study mechanisms of cell signaling and differentiation during development.
Yaniv M. Elkouby, PhD
The vertebrate animal-vegetal (AV) embryonic axis is established already in the oocyte. The hallmark of AV oocyte polarity is differential localization of specific mRNAs to subcellular regions along this axis. While these processes are poorly characterized, evidence implies exciting scenarios of non-conventional AV-mRNA localization modes as the basis of oocyte polarity. Combining advanced live imaging, biochemical and genetic approaches I plan to determine the modes of individual AV-mRNAs localization and identify the localizing regulatory proteins. These experiments will begin to decipher the mechanisms of AV-mRNA localization and early oocyte polarity establishment. I hope to set up this unique experimental system and eventually study these early fascinating developmental processes in my own lab.
My research project is focused on mechanisms acting in the asymmetrical subcellular distribution of RNAs during oogenesis, that determine the establishment of the animal – vegetal polarity in vertebrates. Our laboratory has identified two maternal-effect genes involved in this process: buckyball and microtubule actin crosslinking factor 1 (macf1). By using different molecular and cellular approaches I will determine the interaction between these two genes in the process of RNA asymmetrical localization and I also expect to identify new factors functioning in the pathways responsible for the establishment of the animal-vegetal polarity in zebrafish.
My goal is to address questions relevant to developmental biology using quantitative microscopy and mathematical modeling. My current project focuses on discerning how the various extracellular modulators of Bone Morphogenetic Protein (BMP) shape the robust signaling gradient that patterns the dorsal-ventral axis of zebrafish. I am working on quantitating this BMP morpgogen gradient in various BMP extracellular regulator mutant backrounds. These data will be used to create a system-scale mathmatical model of extracellular BMP regulation.
The creation an maintenance of a developmental axis allows tissues to be correctly placed, and is vital to creating an organism from the onset of oogenesis onward. I am investigating two independent projects about dorsoventral patterning in zebrafish. The first will characterize the temporal and spatial requirements for the localization of maternal mRNAs such as dazl and cyclinB1 in the oocyte, using new cell culture techniques and live imaging. I will also be characterizing the function and mechanism of Ints6, a gene discovered in our lab that acts to restrict the expansion of the dorsal organizer.
Ricardo Fuentes, PhD
I am interested in the molecular mechanisms by which egg components segregate into cytoplasmic domains enriched in maternal factors such as RNAs and proteins during early development. By using zebrafish mutants generated by forward and reverse genetic strategies together with other molecular and cellular approaches, I would like to elucidate the function of unknown factors regulating cytoplasmic movements and how this process prepares the eggs for embryogenesis.
Hannah Greenfeld, PhD
I am interested in how the BMP morphogen gradient patterning the dorsal-ventral axis in the zebrafish embryo is interpreted into different cell fates. Morphogens are thought to pattern developing tissues by inducing differential gene expression in a concentration dependent manner. My goal is to identify direct targets of the BMP signal transducer that respond to distinct levels of BMP signaling. I will examine the nature of chromatin at these target genes during cell specification and as cellular competence to respond to BMP signaling changes during gastrulation.
I'm interested in understanding key regulatory mechanisms that direct the early development of the zebrafish embryo. Fundamental to early development, in invertebrates and vertebrates, is the establishment of the dorsoventral (DV) axis by the Bone Morphogenetic Proteins (BMPs). The BMPs generate a signaling gradient across the entire embryo to specify distinct cell fates. This dynamic and robust gradient of BMP signaling is modulated by various extracellular regulators. I am studying how the extracellular proteins Bmp1a, Tolloid, and Sizzled establish and maintain the BMP signaling gradient. This group of BMP modulators offers unique insight into the spatiotemporal mechanisms that regulate the BMP signaling gradient throughout early development.
In all vertebrates, BMP is a morphogen that instructs cells to adopt specific cell fates, contributing to the establishment of the Dorsal-Ventral axis, as well as many other developmental processes. The BMP ligand communicates to cells by bringing together four transmembrane receptors, two type two receptors and two type one receptors, at the cell surface to form a signalling complex. My project seeks to elucidate the nature of this complex, and to untangle the roles and relative contributions of the zebrafish's many BMP type I and type II receptors in this process.
Hong Zhang, PhD