David Sherwood

Overview:

The Sherwood lab is interested in understanding mechanisms that drive dynamic cellular behaviors underlying normal development and human disease. We study 1) How cells invade into tissues, 2) How stem cells interact with their niches, and 3) How cells control and interact with extracellular matrix. Our lab primarily examines C. elegans development, in which simple cellular complexity, amenability to genetics/genomics/transgenics/molecular perturbations, and evolutionary comparisons facilitates powerful insights. One particular emphasis of our work is live-cell imaging, where we watch cellular behaviors and cell-extracellular matrix interactions unfold in real-time to understand their regulation and function.  Cell invasion, stem cell regulation, and cell-matrix interactions are fundamental to development, regeneration, cancer, and aging.  Our work aims to advance our understanding of these fascinating processes and positively influence human health.

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

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Co-Director of the Duke Regeneration Center

Regeneration Next Initiative
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:

Basement membrane remodeling guides cell migration and cell morphogenesis during development.

Basement membranes (BMs) are thin, dense forms of extracellular matrix that underlie or surround most animal tissues. BMs are enormously complex and harbor numerous proteins that provide essential signaling, mechanical, and barrier support for tissues during their development and normal functioning. As BMs are found throughout animal tissues, cells frequently migrate, change shape, and extend processes along BMs. Although sometimes used only as passive surfaces by cells, studies in developmental contexts are finding that BMs are often actively modified to help guide cell motility and cell morphogenesis. Here, I provide an overview of recent work revealing how BMs are remodeled in remarkably diverse ways to direct cell migration, cell orientation, axon guidance, and dendrite branching events during animal development.
Authors
MLA Citation
Sherwood, David R. “Basement membrane remodeling guides cell migration and cell morphogenesis during development.Current Opinion in Cell Biology, vol. 72, Oct. 2021, pp. 19–27. Epmc, doi:10.1016/j.ceb.2021.04.003.
URI
https://scholars.duke.edu/individual/pub1482913
PMID
34015751
Source
epmc
Published In
Current Opinion in Cell Biology
Volume
72
Published Date
Start Page
19
End Page
27
DOI
10.1016/j.ceb.2021.04.003

Chemical-induced toxicity is ameliorated by swimming exercise in caenorhabditis elegans

Authors
Hartman, J; Smith, L; Gordon, K; Sherwood, D; Laranjeiro, R; Driscoll, M; Meyer, J
MLA Citation
Hartman, Jessica, et al. “Chemical-induced toxicity is ameliorated by swimming exercise in caenorhabditis elegans.” Drug Metabolism and Pharmacokinetics, vol. 34, no. 1, Elsevier BV, 2019, pp. S30–S30. Crossref, doi:10.1016/j.dmpk.2018.09.117.
URI
https://scholars.duke.edu/individual/pub1370564
Source
crossref
Published In
Drug Metabolism and Pharmacokinetics
Volume
34
Published Date
Start Page
S30
End Page
S30
DOI
10.1016/j.dmpk.2018.09.117

Fueling Cell Invasion through Extracellular Matrix.

Cell invasion through extracellular matrix (ECM) has pivotal roles in cell dispersal during development, immune cell trafficking, and cancer metastasis. Many elegant studies have revealed the specialized cellular protrusions, proteases, and distinct modes of migration invasive cells use to overcome ECM barriers. Less clear, however, is how invasive cells provide energy, specifically ATP, to power the energetically demanding membrane trafficking, F-actin polymerization, and actomyosin machinery that mediate break down, remodeling, and movement through ECMs. Here, we provide an overview of the challenges of examining ATP generation and delivery within invading cells and how recent studies using diverse invasion models, experimental approaches, and energy biosensors are revealing that energy metabolism is an integral component of cell invasive behavior that is dynamically tuned to overcome the ECM environment.
Authors
Garde, A; Sherwood, DR
MLA Citation
Garde, Aastha, and David R. Sherwood. “Fueling Cell Invasion through Extracellular Matrix.Trends in Cell Biology, vol. 31, no. 6, June 2021, pp. 445–56. Epmc, doi:10.1016/j.tcb.2021.01.006.
URI
https://scholars.duke.edu/individual/pub1473684
PMID
33549396
Source
epmc
Published In
Trends in Cell Biology
Volume
31
Published Date
Start Page
445
End Page
456
DOI
10.1016/j.tcb.2021.01.006

Breaching the Basement Membrane David R. Sherwood

Authors
MLA Citation
Sherwood, David R. “Breaching the Basement Membrane David R. Sherwood.” Developmental Cell, vol. 49, no. 4, CELL PRESS, May 2019, pp. 498–498.
URI
https://scholars.duke.edu/individual/pub1422498
Source
wos
Published In
Developmental Cell
Volume
49
Published Date
Start Page
498
End Page
498

Cell invasion through basement membrane: The netrin receptor DCC guides the way.

Cell invasion through basement membrane is an essential part of normal development and physiology, and occurs during the pathological progression of human inflammatory diseases and cancer. F-actin-rich membrane protrusions, called invadopodia, have been hypothesized to be the "drill bits" of invasive cells, mediating invasion through the dense, highly cross-linked basement membrane matrix. Though studied in vitro for over 30 y, invadopodia function in vivo has remained elusive. We have recently discovered that invadopodia breach basement membrane during anchor cell invasion in C. elegans, a genetically and visually tractable in vivo invasion event. Further, we found that the netrin receptor DCC localizes to the initial site of basement membrane breach and directs invasion through a single gap in the matrix. In this commentary, we examine how the dynamics and structure of AC-invadopodia compare with in vitro invadopodia and how the netrin receptor guides invasion through a single basement membrane breach. We end with a discussion of our surprising result that the anchor cell pushes the basement membrane aside, instead of completely dissolving it through proteolysis, and provide some ideas for how proteases and physical displacement may work together to ensure efficient and robust invasion.
Authors
Morrissey, MA; Hagedorn, EJ; Sherwood, DR
MLA Citation
Morrissey, Meghan A., et al. “Cell invasion through basement membrane: The netrin receptor DCC guides the way.Worm, vol. 2, no. 3, July 2013, p. e26169. Epmc, doi:10.4161/worm.26169.
URI
https://scholars.duke.edu/individual/pub1030199
PMID
24778942
Source
epmc
Published In
Worm
Volume
2
Published Date
Start Page
e26169
DOI
10.4161/worm.26169