My lab takes an integrative approach to studying organ morphogenesis. We are currently probing how cells migrate collectively & how basement membrane ECMs are assembled.
Collective cell migration - The collective migration of cells within an epithelial sheet underlies tissue remodeling events associated with morphogenesis, wound repair, and the spread of many cancers. Yet little is known about how each epithelial cell coordinates its individual migratory behaviors with those of its neighbors, or how epithelial motility shapes tissues during development. We recently discovered a novel planar signaling system that coordinates leading and trailing edge dynamics between neighboring epithelial cells, and are now working to elucidate the mechanistic basis of this signaling. We are also investigating how collective cell migration can be harnesses to create a stable, planar tissue pattern within an epithelium for subsequent morphogenesis.
Basement membrane dynamics – Basement membrane is a sheet-like extracellular matrix that lines the basal surface of all epithelial tissues. This complex protein network provides structural stability to the monolayer, promotes cell-cell and cell-matrix signaling, and acts as a physical barrier to metastasis. Despite their ubiquity and many essential functions, we know surprisingly little about how basement membranes are built or how they are remodeled during development. We are taking a comprehensive approach to identifying: the cellular mechanisms underlying basement membrane biosynthesis and secretion, how basement membrane biosynthetic programs are modulated to construct diverse matrix architectures, and how different basement membrane architectures ultimately influence organ morphogenesis.
Experimental system – We perform these studies in the Drosophila egg chamber, which is an organ-like structure in the ovary that will give rise to one egg. Each egg chamber is comprised of a germ cell cluster, surrounded by a somatic epithelium of follicle cells. The follicle cells produce their own basement membrane, which ensheaths the organ. Though initially spherical, egg chambers lengthen as they mature. This morphogenesis depends on a dramatic collective migration of the follicle cells across their basement membrane, which causes the entire egg chamber to rotate within its surrounding matrix. Importantly, the follicle cells also remodel the basement membrane as they crawl along its surface, creating a polarized array of fibrils in the direction of tissue movement. This fibrillar matrix is then thought to act as a “molecular corset” that resists the expansive growth of the germ cells to directionally bias egg chamber growth, and thus create the elongated shape of the egg. A major strength of this system is that the collective migration and basement membrane remodeling both occur on the egg chamber’s outer surface, which allows us to image dynamic cell behaviors - in a living organ - with exquisite clarity. Moreover, we can use the sophisticated genetic tools of Drosophila to identify the underlying molecular mechanisms. Please check out the papers below to see what we have already discovered!
UC Berkeley
Postdoc - Cell and Developmental Biology
2008
UC San Francisco
PhD - Biochemistry
2003
University of Oregon
BS - Chemistry
1996
Cortical tension promotes Kibra degradation via Par-1.
Cortical tension promotes Kibra degradation via Par-1. Mol Biol Cell. 2024 Jan 01; 35(1):ar2.
PMID: 37903240
Fat2 polarizes Lar and Sema5c to coordinate the motility of collectively migrating epithelial cells.
Fat2 polarizes Lar and Sema5c to coordinate the motility of collectively migrating epithelial cells. J Cell Sci. 2024 03 01; 137(5).
PMID: 37593878
Fat2 polarizes Lar and Sema5c to coordinate the motility of collectively migrating epithelial cells.
Fat2 polarizes Lar and Sema5c to coordinate the motility of collectively migrating epithelial cells. bioRxiv. 2023 Mar 01.
PMID: 36909523
Optimized Fixation and Phalloidin Staining of Basally Localized F-Actin Networks in Collectively Migrating Follicle Cells.
Optimized Fixation and Phalloidin Staining of Basally Localized F-Actin Networks in Collectively Migrating Follicle Cells. Methods Mol Biol. 2023; 2626:179-191.
PMID: 36715905
A Low-Tech Flow Chamber for Live Imaging of Drosophila Egg Chambers During Drug Treatments.
A Low-Tech Flow Chamber for Live Imaging of Drosophila Egg Chambers During Drug Treatments. Methods Mol Biol. 2023; 2626:277-289.
PMID: 36715910
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration.
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration. Elife. 2022 09 26; 11.
PMID: 36154691
Kinesin-directed secretion of basement membrane proteins to a subdomain of the basolateral surface in Drosophila epithelial cells.
Kinesin-directed secretion of basement membrane proteins to a subdomain of the basolateral surface in Drosophila epithelial cells. Curr Biol. 2022 02 28; 32(4):735-748.e10.
PMID: 35021047
DAAM mediates the assembly of long-lived, treadmilling stress fibers in collectively migrating epithelial cells in Drosophila.
DAAM mediates the assembly of long-lived, treadmilling stress fibers in collectively migrating epithelial cells in Drosophila. Elife. 2021 11 23; 10.
PMID: 34812144
ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms.
ESCargo: a regulatable fluorescent secretory cargo for diverse model organisms. Mol Biol Cell. 2020 12 15; 31(26):2892-2903.
PMID: 33112725
The Drosophila micropyle as a system to study how epithelia build complex extracellular structures.
The Drosophila micropyle as a system to study how epithelia build complex extracellular structures. Philos Trans R Soc Lond B Biol Sci. 2020 10 12; 375(1809):20190561.
PMID: 32829690
Quantrell Award for Excellence in Undergraduate Teaching
The University of Chicago
2021
Basil O'Connor Starter Scholar Research Award
The March of Dimes Foundation
2010 - 2012
Young Investigator Award
Edward Mallinckrodt, Jr. Foundation
2009 - 2012
Postdoctoral Fellowship
Jane Coffin Childs Foundation
2003 - 2006
Harold C. Weintraub Graduate Student Award
Fred Hutchinson Cancer Center
2003
Predoctoral Fellowship
American Heart Association
2001 - 2003
Predoctoral Fellowship
National Science Foundation
1998 - 2001
American Foundation of Chemists Award
University of Oregon
1996
Graduated summa cum laude and with Departmental Honors
University of Oregon
1996