David Sherwood

Overview:

Our research is directed at elucidating mechanisms underlying morphogenetic processes in development. We primarily use the model system C. elegans in our research, and combine powerful genetic and systems biology approaches with live-cell imaging to address three main topics: 
  •  Tissue Remodeling and Connection
A major focus of the lab is the understanding of mechanisms underlying uterine-vulval attachment. A key aspect of this process is the invasion of a single uterine cell, the anchor cell, through the uterine and vulval basement membranes, which initiates uterine-vulval connection. The ability of cells to invade through basement membrane is crucial for many developmental processes and remains one of the least understood aspects in the progression of cancer. We have begun to apply what we learn in the anchor cell to better understand how cancer cells become invasive. Our group also examines other aspects of uterine-vulval attachment, including control of cell division, cell-cell signaling, cell-cell attachments and basement membrane remodeling. 
  • Stem Cell-Niche Interactions
We are examining the cell biological aspects of cell-cell and cell-basement membrane establishment of the germ stem cell niche. We are particularly interested in how somatic and germ cells interact to maintain the germ stem cells. We have made the surprising discovery that germ cells that escape their niche appear capable of inducing naïve somatic cells to take on the role of the niche cells. We are conducting screens and performing live-cell imaging studies to understand this novel behavior.

  • Nutritional Regulation of Late Larval Development 
In collaboration with Dr. Ryan Baugh's lab, we are examining the developmental response of late larvae to starvation. We have identified specific developmental checkpoints that larvae enter in response to the absence of food. These studies have many fascinating implications in our understanding of how cells arrest at specific developmental time-points, how an organism and cells enter and exit quiescent states, and how these impinge on life-span. 

Members of our group are trained in a diverse range of scientific approaches and join a vibrant scientific community at Duke University, the Research Triangle region and the worldwide group of worm researchers.

Positions:

Jerry G. and Patricia Crawford Hubbard Professor

Biology
Trinity College of Arts & Sciences

Professor of Biology

Biology
Trinity College of Arts & Sciences

Associate Professor in Cell Biology

Cell Biology
School of Medicine

Co-Director of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.A. 1990

Wesleyan University

Ph.D. 1997

Duke University

Grants:

Understanding the role of the collagen receptor DDR-2 in germ stem cell niche formation

Administered By
Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Understanding how cells invade through basement membrane in vivo

Administered By
Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Defining a Newly Identified Membrane Structure That Directs Cell Invasion

Administered By
Biology
Role
Principal Investigator
Start Date
End Date

Understanding how innexins direct stem cell niche morphology

Administered By
Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Visualizing and Elucidating the Role of Force on Type IV Collagen in Development

Administered By
Biology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling.

Epithelial cells and their underlying basement membranes (BMs) slide along each other to renew epithelia, shape organs, and enlarge BM openings. How BM sliding is controlled, however, is poorly understood. Using genetic and live cell imaging approaches during uterine-vulval attachment in C. elegans, we have discovered that the invasive uterine anchor cell activates Notch signaling in neighboring uterine cells at the boundary of the BM gap through which it invades to promote BM sliding. Through an RNAi screen, we found that Notch activation upregulates expression of ctg-1, which encodes a Sec14-GOLD protein, a member of the Sec14 phosphatidylinositol-transfer protein superfamily that is implicated in vesicle trafficking. Through photobleaching, targeted knockdown, and cell-specific rescue, our results suggest that CTG-1 restricts BM adhesion receptor DGN-1 (dystroglycan) trafficking to the cell-BM interface, which promotes BM sliding. Together, these studies reveal a new morphogenetic signaling pathway that controls BM sliding to remodel tissues.
Authors
McClatchey, ST; Wang, Z; Linden, LM; Hastie, EL; Wang, L; Shen, W; Chen, A; Chi, Q; Sherwood, DR
MLA Citation
McClatchey, Shelly Th, et al. “Boundary cells restrict dystroglycan trafficking to control basement membrane sliding during tissue remodeling..” Elife, vol. 5, Sept. 2016. Epmc, doi:10.7554/eLife.17218.
URI
https://scholars.duke.edu/individual/pub1146663
PMID
27661254
Source
epmc
Published In
Elife
Volume
5
Published Date
DOI
10.7554/eLife.17218

Investigating the B-LINK: an adhesion system that links neighboring basement membranes.

Authors
Keeley, DP; Morrissey, M; Sherwood, DR
MLA Citation
Keeley, D. P., et al. “Investigating the B-LINK: an adhesion system that links neighboring basement membranes..” Molecular Biology of the Cell, vol. 25, AMER SOC CELL BIOLOGY, 2014.
URI
https://scholars.duke.edu/individual/pub1071454
Source
wos
Published In
Molecular Biology of the Cell
Volume
25
Published Date

Patterning of cell cycle arrest during formation of the nematode uterine-vulval connection

Authors
MLA Citation
Matus, D. Q., et al. “Patterning of cell cycle arrest during formation of the nematode uterine-vulval connection.” Integrative and Comparative Biology, vol. 53, OXFORD UNIV PRESS INC, 2013, pp. E139–E139.
URI
https://scholars.duke.edu/individual/pub945276
Source
wos
Published In
Integrative and Comparative Biology
Volume
53
Published Date
Start Page
E139
End Page
E139

Imaging the Cell-Basement Membrane Interface during Anchor Cell Invasion in C. elegans

Authors
Hagedorn, EJ; Sherwood, DR
MLA Citation
Hagedorn, E. J., and D. R. Sherwood. “Imaging the Cell-Basement Membrane Interface during Anchor Cell Invasion in C. elegans.” Molecular Biology of the Cell, vol. 22, AMER SOC CELL BIOLOGY, 2011.
URI
https://scholars.duke.edu/individual/pub912758
Source
wos
Published In
Molecular Biology of the Cell
Volume
22
Published Date

Gene expression markers for Caenorhabditis elegans vulval cells.

The analysis of cell fate patterning during the vulval development of Caenorhabditis elegans has relied mostly on the direct observation of cell divisions and cell movements (cell lineage analysis). However, reconstruction of the developing vulva from EM serial sections has suggested seven different cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), many of which cannot be distinguished based on such observations. Here we report the vulval expression of seven genes, egl-17, cdh-3, ceh-2, zmp-1, B0034.1, T04B2.6 and F47B8.6 based on gfp, cfp and yfp (green fluorescent protein and color variants) reporter fusions. Each gene expresses in a specific subset of vulval cells, and is therefore useful as a marker for vulval cell fates. Together, expressions of markers distinguish six cell types, and reveal a strict temporal control of gene expression in the developing vulva.
Authors
Inoue, T; Sherwood, DR; Aspöck, G; Butler, JA; Gupta, BP; Kirouac, M; Wang, M; Lee, P-Y; Kramer, JM; Hope, I; Bürglin, TR; Sternberg, PW
MLA Citation
Inoue, Takao, et al. “Gene expression markers for Caenorhabditis elegans vulval cells..” Gene Expression Patterns : Gep, vol. 2, no. 3–4, Dec. 2002, pp. 235–41. Epmc, doi:10.1016/s1567-133x(02)00055-8.
URI
https://scholars.duke.edu/individual/pub657126
PMID
12617807
Source
epmc
Published In
Gene Expression Patterns : Gep
Volume
2
Published Date
Start Page
235
End Page
241
DOI
10.1016/s1567-133x(02)00055-8