Donald Fox

Positions:

Associate Professor of Pharmacology & Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Assistant Professor in Cell Biology

Cell Biology
School of Medicine

Associate of the Duke Initiative for Science & Society

Duke Science & Society
Institutes and Provost's Academic Units

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

B.S. 2000

College of William and Mary

Ph.D. 2006

University of North Carolina at Chapel Hill

Grants:

Hypertrophy vs. Proliferation Following Tissue Injury: A Drosophila Model

Administered By
Pharmacology & Cancer Biology
Awarded By
American Heart Association
Role
Principal Investigator
Start Date
End Date

Impact of polyploidy on establishing an HIV-1 reservoir in the kidney

Administered By
Medicine, Infectious Diseases
Awarded By
University of Alabama at Birmingham
Role
Principal Investigator
Start Date
End Date

Par-4 Regulation and Function in Breast Cancer Dormancy and Recurrence

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Publications:

Model systems for regeneration: Drosophila.

Drosophila melanogaster has historically been a workhorse model organism for studying developmental biology. In addition, Drosophila is an excellent model for studying how damaged tissues and organs can regenerate. Recently, new precision approaches that enable both highly targeted injury and genetic manipulation have accelerated progress in this field. Here, we highlight these techniques and review examples of recently discovered mechanisms that regulate regeneration in Drosophila larval and adult tissues. We also discuss how, by applying these powerful approaches, studies of Drosophila can continue to guide the future of regeneration research.
Authors
Fox, DT; Cohen, E; Smith-Bolton, R
MLA Citation
Fox, Donald T., et al. “Model systems for regeneration: Drosophila.Development, vol. 147, no. 7, Apr. 2020. Pubmed, doi:10.1242/dev.173781.
URI
https://scholars.duke.edu/individual/pub1436714
PMID
32253254
Source
pubmed
Published In
Development
Volume
147
Published Date
DOI
10.1242/dev.173781

Exploiting codon usage identifies RpS21 as an in vivo signal strength-dependent Ras/MAPK regulator

ABSTRACT Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. We mapped the underlying gene from one modifier to the ribosomal gene RpS21 . RpS21 preferentially influences weak Ras/MAPK signaling outputs, and negatively regulates Ras/MAPK in multiple cell/tissue and signaling settings. In turn, MAPK signaling may regulate its own negative feedback by promoting RpS21 expression. These data show that codon usage manipulation can identify output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator.
Authors
Sawyer, J; Kabiri, Z; Montague, R; Paramore, S; Cohen, E; Zaribafzadeh, H; Counter, C; Fox, D
MLA Citation
URI
https://scholars.duke.edu/individual/pub1404008
Source
epmc
Published Date
DOI
10.1101/650630

Interorgan regulation of Drosophila intestinal stem cell proliferation by a hybrid organ boundary zone.

The molecular identities and regulation of cells at interorgan boundaries are often unclear, despite the increasingly appreciated role of organ boundaries in disease. Using Drosophila as a model, we here show that a specific population of adult midgut organ-boundary intestinal stem cells (OB-ISCs) is regulated by the neighboring hindgut, a developmentally distinct organ. This distinct OB-ISC control occurs through proximity to a specialized transition zone between the endodermal midgut and ectodermal hindgut that shares molecular signatures of both organs, which we term the hybrid zone (HZ). During homeostasis, proximity to the HZ restrains OB-ISC proliferation. However, injury to the adult HZ/hindgut drives upregulation of unpaired-3 cytokine, which signals through a Signal transducer and activator of transcription (STAT) protein to promote cell division only in OB-ISCs. If HZ disruption is severe, hyperplastic OB-ISCs expand across the interorgan boundary. Our data suggest that interorgan signaling plays an important role in controlling OB-ISCs in homeostasis and injury repair, which is likely to be crucial in prevention of disease.
Authors
Sawyer, JK; Cohen, E; Fox, DT
MLA Citation
Sawyer, Jessica K., et al. “Interorgan regulation of Drosophila intestinal stem cell proliferation by a hybrid organ boundary zone.Development, vol. 144, no. 22, Nov. 2017, pp. 4091–102. Pubmed, doi:10.1242/dev.153114.
URI
https://scholars.duke.edu/individual/pub1277834
PMID
28947534
Source
pubmed
Published In
Development
Volume
144
Published Date
Start Page
4091
End Page
4102
DOI
10.1242/dev.153114

Balancing different types of actin polymerization at distinct sites: roles for Abelson kinase and Enabled.

The proto-oncogenic kinase Abelson (Abl) regulates actin in response to cell signaling. Drosophila Abl is required in the nervous system, and also in epithelial cells, where it regulates adherens junction stability and actin organization. Abl acts at least in part via the actin regulator Enabled (Ena), but the mechanism by which Abl regulates Ena is unknown. We describe a novel role for Abl in early Drosophila development, where it regulates the site and type of actin structures produced. In Abl's absence, excess actin is polymerized in apical microvilli, whereas too little actin is assembled into pseudocleavage and cellularization furrows. These effects involve Ena misregulation. In abl mutants, Ena accumulates ectopically at the apical cortex where excess actin is observed, suggesting that Abl regulates Ena's subcellular localization. We also examined other actin regulators. Loss of Abl leads to changes in the localization of the Arp2/3 complex and the formin Diaphanous, and mutations in diaphanous or capping protein beta enhance abl phenotypes.
Authors
Grevengoed, EE; Fox, DT; Gates, J; Peifer, M
MLA Citation
Grevengoed, Elizabeth E., et al. “Balancing different types of actin polymerization at distinct sites: roles for Abelson kinase and Enabled.J Cell Biol, vol. 163, no. 6, Dec. 2003, pp. 1267–79. Pubmed, doi:10.1083/jcb.200307026.
URI
https://scholars.duke.edu/individual/pub771702
PMID
14676307
Source
pubmed
Published In
The Journal of Cell Biology
Volume
163
Published Date
Start Page
1267
End Page
1279
DOI
10.1083/jcb.200307026

Polyteny: still a giant player in chromosome research.

In this era of high-resolution mapping of chromosome territories, topological interactions, and chromatin states, it is increasingly appreciated that the positioning of chromosomes and their interactions within the nucleus is critical for cellular function. Due to their large size and distinctive structure, polytene chromosomes have contributed a wealth of knowledge regarding chromosome regulation. In this review, we discuss the diversity of polytene chromosomes in nature and in disease, examine the recurring structural features of polytene chromosomes in terms of what they reveal about chromosome biology, and discuss recent advances regarding how polytene chromosomes are assembled and disassembled. After over 130 years of study, these giant chromosomes are still powerful tools to understand chromosome biology.
Authors
Stormo, BM; Fox, DT
MLA Citation
Stormo, Benjamin M., and Donald T. Fox. “Polyteny: still a giant player in chromosome research.Chromosome Res, vol. 25, no. 3–4, Oct. 2017, pp. 201–14. Pubmed, doi:10.1007/s10577-017-9562-z.
URI
https://scholars.duke.edu/individual/pub1269525
PMID
28779272
Source
pubmed
Published In
Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology
Volume
25
Published Date
Start Page
201
End Page
214
DOI
10.1007/s10577-017-9562-z

Research Areas:

Aneuploidy
Cell Cycle
Gene Dosage
Genome
Genomic Instability
Image Processing, Computer-Assisted
Microscopy, Confocal
Polyploidy
Transcriptome