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
Awarded By
American Cancer Society, Inc.
Role
Principal Investigator
Start Date
End Date

Understanding a Novel Role for Gap Junctions in Directing Endogenous and Ectopic 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:

The role of lipid metabolism in anchor cell invasion in C.elegans

Authors
Garde, A; Li, Y; Sherwood, DR
MLA Citation
Garde, A., et al. “The role of lipid metabolism in anchor cell invasion in C.elegans.” Molecular Biology of the Cell, vol. 29, no. 26, AMER SOC CELL BIOLOGY, 2018, pp. 238–39.
URI
https://scholars.duke.edu/individual/pub1428920
Source
wos
Published In
Molecular Biology of the Cell
Volume
29
Published Date
Start Page
238
End Page
239

Should I stay or should I go? Identification of novel nutritionally regulated developmental checkpoints in C. elegans.

After embryogenesis, developing organisms typically secure their own nutrients to enable further growth. The fitness of an organism depends on developing when food is abundant and slowing or stopping development during periods of scarcity. Although several key pathways that link nutrition with development have been identified, a mechanistic understanding of how these pathways coordinate growth with nutritional conditions is lacking. We took advantage of the stereotyped development and experimental accessibility of C. elegans to study nutritional control of late larval development. We discovered that C. elegans larval development is punctuated by precisely time checkpoints that globally arrest growth when nutritional conditions are unfavorable. Arrest at the checkpoints is regulated by insulin- and insulin-like signaling and steroid hormone signaling. These pathways are conserved in mammals, suggesting that similar mechanisms could regulate growth and development in humans. We highlight several implications of our research, including quiescence of diverse cellular behaviors as an adaptive response to unfavorable growth conditions, the existence of oscillatory checkpoints that coordinate development across tissues, and the connections between systemic and cell-autonomous regulators of nutritional response. Together, our findings describe a fascinating developmental strategy in C. elegans that we expect will not only provide insight into nutritional regulation of development, but also into poorly understood cellular processes such as quiescence and aging.
Authors
Schindler, AJ; Sherwood, DR
MLA Citation
Schindler, Adam J., and David R. Sherwood. “Should I stay or should I go? Identification of novel nutritionally regulated developmental checkpoints in C. elegans.Worm, vol. 3, no. 4, Oct. 2014, p. e979658. Epmc, doi:10.4161/21624054.2014.979658.
URI
https://scholars.duke.edu/individual/pub1096694
PMID
26430552
Source
epmc
Published In
Worm
Volume
3
Published Date
Start Page
e979658
DOI
10.4161/21624054.2014.979658

Stem cell niche exit in C. elegans via orientation and segregation of daughter cells by a cryptic cell outside the niche.

Stem cells reside in and rely upon their niche to maintain stemness but must balance self-renewal with the production of daughters that leave the niche to differentiate. We discovered a mechanism of stem cell niche exit in the canonical C. elegans distal tip cell (DTC) germ stem cell niche mediated by previously unobserved, thin, membranous protrusions of the adjacent somatic gonad cell pair (Sh1). A disproportionate number of germ cell divisions were observed at the DTC-Sh1 interface. Stem-like and differentiating cell fates segregated across this boundary. Spindles polarized, pairs of daughter cells oriented between the DTC and Sh1, and Sh1 grew over the Sh1-facing daughter. Impeding Sh1 growth by RNAi to cofilin and Arp2/3 perturbed the DTC-Sh1 interface, reduced germ cell proliferation, and shifted a differentiation marker. Because Sh1 membrane protrusions eluded detection for decades, it is possible that similar structures actively regulate niche exit in other systems.
Authors
Gordon, KL; Zussman, JW; Li, X; Miller, C; Sherwood, DR
MLA Citation
Gordon, Kacy L., et al. “Stem cell niche exit in C. elegans via orientation and segregation of daughter cells by a cryptic cell outside the niche.Elife, vol. 9, July 2020. Epmc, doi:10.7554/elife.56383.
URI
https://scholars.duke.edu/individual/pub1452215
PMID
32692313
Source
epmc
Published In
Elife
Volume
9
Published Date
DOI
10.7554/elife.56383

Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding.

Basement membranes (BMs) are supramolecular matrices built on laminin and type IV collagen networks that provide structural and signaling support to tissues. BM complexity, however, has hindered an understanding of its formation, dynamics, and regulation. Using genome editing, we tagged 29 BM matrix components and receptors in C. elegans with mNeonGreen. Here, we report a common template that initiates BM formation, which rapidly diversifies during tissue differentiation. Through photobleaching studies, we show that BMs are not static-surprisingly, many matrix proteins move within the laminin and collagen scaffoldings. Finally, quantitative imaging, conditional knockdown, and optical highlighting indicate that papilin, a poorly studied glycoprotein, is the most abundant component in the gonadal BM, where it facilitates type IV collagen removal during BM expansion and tissue growth. Together, this work introduces methods for holistic investigation of BM regulation and reveals that BMs are highly dynamic and capable of rapid change to support tissues.
Authors
Keeley, DP; Hastie, E; Jayadev, R; Kelley, LC; Chi, Q; Payne, SG; Jeger, JL; Hoffman, BD; Sherwood, DR
MLA Citation
Keeley, Daniel P., et al. “Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding.Developmental Cell, vol. 54, no. 1, July 2020, pp. 60-74.e7. Epmc, doi:10.1016/j.devcel.2020.05.022.
URI
https://scholars.duke.edu/individual/pub1448839
PMID
32585132
Source
epmc
Published In
Developmental Cell
Volume
54
Published Date
Start Page
60
End Page
74.e7
DOI
10.1016/j.devcel.2020.05.022

Endogenous expression of UNC-59/Septin in C. elegans.

Authors
Chen, D; Hastie, E; Sherwood, D
MLA Citation
Chen, David, et al. “Endogenous expression of UNC-59/Septin in C. elegans.Micropublication Biology, vol. 2019, Dec. 2019. Epmc, doi:10.17912/micropub.biology.000200.
URI
https://scholars.duke.edu/individual/pub1448210
PMID
32550451
Source
epmc
Published In
Micropublication Biology
Volume
2019
Published Date
DOI
10.17912/micropub.biology.000200