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Donald T Fox

Professor of Pharmacology & Cancer Biology
Pharmacology & Cancer Biology
3813, C318 LSRC, Durham, NC 27710
DUMC Box 3813, Levine Science Research Center, Durham, NC 27710

Selected Publications


Broken chromosomes heading into mitosis: More than one way to patch a flat tire.

Journal Article J Cell Biol · April 1, 2024 A cell dealing with a broken chromosome in mitosis is like a driver dealing with a flat tire on the highway: damage repair must occur under non-ideal circumstances. Mitotic chromosome breaks encounter problems related to structures called micronuclei. Thes ... Full text Link to item Cite

Conserved chamber-specific polyploidy maintains heart function in Drosophila.

Journal Article Development · August 15, 2023 Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy level ... Full text Link to item Cite

Conserved Chamber-Specific Polyploidy Maintains Heart Function in Drosophila.

Journal Article bioRxiv · February 11, 2023 Developmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, we reveal roles for precise polyploidy levels in cardiac tissue. We highlight a conse ... Full text Link to item Cite

Measuring Cellular Ploidy In Situ by Light Microscopy.

Journal Article Methods Mol Biol · 2023 Determining cellular DNA content is valuable in the study of numerous biological processes, including organ development and injury repair. While FACS analysis of dissociated cells is a widely used method for assaying ploidy in a tissue cell population, for ... Full text Link to item Cite

Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel.

Journal Article Life Sci Space Res (Amst) · November 2022 Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human heal ... Full text Link to item Cite

Conserved function of Drosophila Fancd2 monoubiquitination in response to double-strand DNA breaks.

Journal Article G3 (Bethesda, Md.) · July 2022 Fanconi anemia genes play key roles in metazoan DNA damage responses, and human FA mutations cause numerous disease phenotypes. In human cells, activating monoubiquitination of the Fanconi anemia protein Fancd2 occurs following diverse DNA damage stimuli. ... Full text Cite

Distinct responses to rare codons in select Drosophila tissues.

Journal Article Elife · May 6, 2022 Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wi ... Full text Link to item Cite

Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation.

Journal Article J Cell Biol · December 6, 2021 Cycling cells must respond to DNA double-strand breaks (DSBs) to avoid genome instability. Missegregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is inc ... Full text Link to item Cite

Communal living: the role of polyploidy and syncytia in tissue biology.

Journal Article Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · December 2021 Multicellular organisms are composed of tissues with diverse cell sizes. Whether a tissue primarily consists of numerous, small cells as opposed to fewer, large cells can impact tissue development and function. The addition of nuclear genome copies within ... Full text Cite

DNA Damage Responses during the Cell Cycle: Insights from Model Organisms and Beyond.

Journal Article Genes (Basel) · November 25, 2021 Genome damage is a threat to all organisms. To respond to such damage, DNA damage responses (DDRs) lead to cell cycle arrest, DNA repair, and cell death. Many DDR components are highly conserved, whereas others have adapted to specific organismal needs. Im ... Full text Link to item Cite

Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut.

Journal Article Dev Cell · July 26, 2021 Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division cycles in a developing organ occur on a relatively fixed timescale. Despite this, many developing organs can regenerate cel ... Full text Link to item Cite

Persistent DNA Repair Signaling and DNA Polymerase Theta Promote Broken Chromosome Segregation

Journal Article · 2021 Cycling cells must respond to double-strand breaks (DSBs) to avoid genome instability. Mis-segregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incomp ... Full text Cite

Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo.

Journal Article PLoS Genet · December 2020 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. ... Full text Link to item Cite

Cytoplasmic sharing through apical membrane remodeling.

Journal Article Elife · October 14, 2020 Multiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In contrast, we discover ... Full text Link to item Cite

Polyploidy: A Biological Force From Cells to Ecosystems.

Journal Article Trends Cell Biol · September 2020 Polyploidy, resulting from the duplication of the entire genome of an organism or cell, greatly affects genes and genomes, cells and tissues, organisms, and even entire ecosystems. Despite the wide-reaching importance of polyploidy, communication across di ... Full text Link to item Cite

Model systems for regeneration: Drosophila.

Journal Article Development · April 6, 2020 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 e ... Full text Link to item Cite

Physiology, Development, and Disease Modeling in the Drosophila Excretory System.

Journal Article Genetics · February 2020 The insect excretory system contains two organ systems acting in concert: the Malpighian tubules and the hindgut perform essential roles in excretion and ionic and osmotic homeostasis. For over 350 years, these two organs have fascinated biologists as a mo ... Full text Link to item Cite

Accelerated cell cycles enable organ regeneration under developmental time constraints in theDrosophilahindgut

Journal Article · 2020 Summary Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division in a developing organ occurs on a relatively fixed time scale. Despite this, many developing organs can re ... Full text Cite

Broken chromosomes heading into mitosis: More than one way to patch a flat tire.

Journal Article J Cell Biol · April 1, 2024 A cell dealing with a broken chromosome in mitosis is like a driver dealing with a flat tire on the highway: damage repair must occur under non-ideal circumstances. Mitotic chromosome breaks encounter problems related to structures called micronuclei. Thes ... Full text Link to item Cite

Conserved chamber-specific polyploidy maintains heart function in Drosophila.

Journal Article Development · August 15, 2023 Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy level ... Full text Link to item Cite

Conserved Chamber-Specific Polyploidy Maintains Heart Function in Drosophila.

Journal Article bioRxiv · February 11, 2023 Developmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, we reveal roles for precise polyploidy levels in cardiac tissue. We highlight a conse ... Full text Link to item Cite

Measuring Cellular Ploidy In Situ by Light Microscopy.

Journal Article Methods Mol Biol · 2023 Determining cellular DNA content is valuable in the study of numerous biological processes, including organ development and injury repair. While FACS analysis of dissociated cells is a widely used method for assaying ploidy in a tissue cell population, for ... Full text Link to item Cite

Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel.

Journal Article Life Sci Space Res (Amst) · November 2022 Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human heal ... Full text Link to item Cite

Conserved function of Drosophila Fancd2 monoubiquitination in response to double-strand DNA breaks.

Journal Article G3 (Bethesda, Md.) · July 2022 Fanconi anemia genes play key roles in metazoan DNA damage responses, and human FA mutations cause numerous disease phenotypes. In human cells, activating monoubiquitination of the Fanconi anemia protein Fancd2 occurs following diverse DNA damage stimuli. ... Full text Cite

Distinct responses to rare codons in select Drosophila tissues.

Journal Article Elife · May 6, 2022 Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wi ... Full text Link to item Cite

Persistent DNA damage signaling and DNA polymerase theta promote broken chromosome segregation.

Journal Article J Cell Biol · December 6, 2021 Cycling cells must respond to DNA double-strand breaks (DSBs) to avoid genome instability. Missegregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is inc ... Full text Link to item Cite

Communal living: the role of polyploidy and syncytia in tissue biology.

Journal Article Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · December 2021 Multicellular organisms are composed of tissues with diverse cell sizes. Whether a tissue primarily consists of numerous, small cells as opposed to fewer, large cells can impact tissue development and function. The addition of nuclear genome copies within ... Full text Cite

DNA Damage Responses during the Cell Cycle: Insights from Model Organisms and Beyond.

Journal Article Genes (Basel) · November 25, 2021 Genome damage is a threat to all organisms. To respond to such damage, DNA damage responses (DDRs) lead to cell cycle arrest, DNA repair, and cell death. Many DDR components are highly conserved, whereas others have adapted to specific organismal needs. Im ... Full text Link to item Cite

Accelerated cell cycles enable organ regeneration under developmental time constraints in the Drosophila hindgut.

Journal Article Dev Cell · July 26, 2021 Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division cycles in a developing organ occur on a relatively fixed timescale. Despite this, many developing organs can regenerate cel ... Full text Link to item Cite

Persistent DNA Repair Signaling and DNA Polymerase Theta Promote Broken Chromosome Segregation

Journal Article · 2021 Cycling cells must respond to double-strand breaks (DSBs) to avoid genome instability. Mis-segregation of chromosomes with DSBs during mitosis results in micronuclei, aberrant structures linked to disease. How cells respond to DSBs during mitosis is incomp ... Full text Cite

Exploiting codon usage identifies intensity-specific modifiers of Ras/MAPK signaling in vivo.

Journal Article PLoS Genet · December 2020 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. ... Full text Link to item Cite

Cytoplasmic sharing through apical membrane remodeling.

Journal Article Elife · October 14, 2020 Multiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In contrast, we discover ... Full text Link to item Cite

Polyploidy: A Biological Force From Cells to Ecosystems.

Journal Article Trends Cell Biol · September 2020 Polyploidy, resulting from the duplication of the entire genome of an organism or cell, greatly affects genes and genomes, cells and tissues, organisms, and even entire ecosystems. Despite the wide-reaching importance of polyploidy, communication across di ... Full text Link to item Cite

Model systems for regeneration: Drosophila.

Journal Article Development · April 6, 2020 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 e ... Full text Link to item Cite

Physiology, Development, and Disease Modeling in the Drosophila Excretory System.

Journal Article Genetics · February 2020 The insect excretory system contains two organ systems acting in concert: the Malpighian tubules and the hindgut perform essential roles in excretion and ionic and osmotic homeostasis. For over 350 years, these two organs have fascinated biologists as a mo ... Full text Link to item Cite

Accelerated cell cycles enable organ regeneration under developmental time constraints in theDrosophilahindgut

Journal Article · 2020 Summary Individual organ development must be temporally coordinated with development of the rest of the organism. As a result, cell division in a developing organ occurs on a relatively fixed time scale. Despite this, many developing organs can re ... Full text Cite

Cytoplasmic sharing through apical membrane remodeling

Journal Article · 2020 ABSTRACT Multiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In con ... Full text Cite

Toxicological Study and Genetic Basis of BTEX Susceptibility in Drosophila melanogaster.

Journal Article Front Genet · 2020 Benzene, toluene, ethylbenzene and xylene, also known as BTEX, are released into environmental media by petroleum product exploratory and exploitative activities and are harmful to humans and animals. Testing the effects of these chemicals on a significant ... Full text Link to item Cite

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

Journal Article · May 26, 2019 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 reg ... Full text Cite

Interphase cohesin regulation ensures mitotic fidelity after genome reduplication.

Journal Article Mol Biol Cell · January 15, 2019 To ensure faithful genome propagation, mitotic cells alternate one round of chromosome duplication with one round of chromosome separation. Chromosome separation failure thus causes genome reduplication, which alters mitotic chromosome structure. Such stru ... Full text Link to item Cite

Fizzy-Related dictates A cell cycle switch during organ repair and tissue growth responses in the Drosophila hindgut.

Journal Article Elife · August 17, 2018 Ploidy-increasing cell cycles drive tissue growth in many developing organs. Such cycles, including endocycles, are increasingly appreciated to drive tissue growth following injury or activated growth signaling in mature organs. In these organs, the regula ... Full text Link to item Cite

Polyploidy and Mitotic Cell Death Are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells.

Journal Article J Virol · January 15, 2018 Prior studies have found that HIV, through the Vpr protein, promotes genome reduplication (polyploidy) in infection-surviving epithelial cells within renal tissue. However, the temporal progression and molecular regulation through which Vpr promotes polypl ... Full text Link to item Cite

A Cell Cycle Switch Dictates Organ Repair and Tissue Growth Responses in TheDrosophilaHindgut

Journal Article · 2018 ABSTRACT Ploidy-increasing cell cycles drive tissue growth in many developing organs. Such cycles, including endocycles, are increasingly appreciated to drive tissue growth following injury or activated growth signaling in mature organs. In these ... Full text Cite

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

Journal Article Development · November 15, 2017 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 orga ... Full text Link to item Cite

Polyteny: still a giant player in chromosome research.

Journal Article Chromosome Res · October 2017 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 ... Full text Link to item Cite

Inter-organ regulation ofDrosophilaintestinal stem cell proliferation by a hybrid organ boundary zone

Journal Article · 2017 SUMMARY STATEMENT Gene expression at the Drosophila midgut-hindgut boundary is a hybrid of both organs. Hybrid cells repress stem cell division, but boundary injury activates stem cell division through inter-organ JAK-STAT signaling. ABSTRACT< ... Full text Cite

Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2.

Journal Article Dev Cell · June 6, 2016 Conserved DNA-damage responses (DDRs) sense genome damage and prevent mitosis of broken chromosomes. How cells lacking DDRs cope with broken chromosomes during mitosis is poorly understood. DDRs are frequently inactivated in cells with extra genomes (polyp ... Full text Link to item Cite

Distinct responses to reduplicated chromosomes require distinct Mad2 responses.

Journal Article Elife · May 9, 2016 Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromoso ... Full text Link to item Cite

The expanding implications of polyploidy.

Journal Article J Cell Biol · May 25, 2015 Polyploid cells, which contain more than two genome copies, occur throughout nature. Beyond well-established roles in increasing cell size/metabolic output, polyploidy can also promote nonuniform genome, transcriptome, and metabolome alterations. Polyploid ... Full text Link to item Cite

Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum.

Journal Article Development · September 2014 The endocycle is a modified cell cycle that lacks M phase. Endocycles are well known for enabling continued growth of post-mitotic tissues. By contrast, we discovered pre-mitotic endocycles in precursors of Drosophila rectal papillae (papillar cells). Unli ... Full text Link to item Cite

Polyploidization and cell fusion contribute to wound healing in the adult Drosophila epithelium.

Journal Article Curr Biol · November 18, 2013 BACKGROUND: Reestablishing epithelial integrity and biosynthetic capacity is critically important following tissue damage. The adult Drosophila abdominal epithelium provides an attractive new system to address how postmitotic diploid cells contribute to re ... Full text Link to item Cite

Endoreplication and polyploidy: insights into development and disease.

Journal Article Development · January 1, 2013 Polyploid cells have genomes that contain multiples of the typical diploid chromosome number and are found in many different organisms. Studies in a variety of animal and plant developmental systems have revealed evolutionarily conserved mechanisms that co ... Full text Link to item Cite

Drosophila stem cell niches: a decade of discovery suggests a unified view of stem cell regulation.

Journal Article Dev Cell · July 19, 2011 The past decade of research on Drosophila stem cells and niches has provided key insights. Fly stem cells do not occupy a special "state" based on novel "stem cell genes" but resemble transiently arrested tissue progenitors. Moreover, individual stem cells ... Full text Link to item Cite

Error-prone polyploid mitosis during normal Drosophila development.

Journal Article Genes Dev · October 15, 2010 Endopolyploidy arises during normal development in many species when cells undergo endocycles-variant cell cycles in which DNA replicates but daughter cells do not form. Normally, polyploid cells do not divide mitotically after initiating endocycles; hence ... Full text Link to item Cite

The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage.

Journal Article Cell Stem Cell · September 4, 2009 The adult Drosophila hindgut was recently reported to contain active, tissue-replenishing stem cells, like those of the midgut, but located within an anterior ring so as to comprise a single giant crypt. In contrast to this view, we observed no active stem ... Full text Link to item Cite

Lineage analysis of stem cells

Journal Article StemBook · 2009 Full text Cite

Using Bcr-Abl to examine mechanisms by which abl kinase regulates morphogenesis in Drosophila.

Journal Article Mol Biol Cell · January 2008 Signaling by the nonreceptor tyrosine kinase Abelson (Abl) plays key roles in normal development, whereas its inappropriate activation helps trigger the development of several forms of leukemia. Abl is best known for its roles in axon guidance, but Abl and ... Full text Link to item Cite

Stem cells and their niches: integrated units that maintain Drosophila tissues.

Journal Article Cold Spring Harb Symp Quant Biol · 2008 The genetic analysis of four distinct Drosophila stem cells and their niches has revealed principles of stem cell biology that are likely to apply widely. A stem cell and its niche act together as integral parts of a system that supplies replacement cells ... Full text Link to item Cite

Abelson kinase (Abl) and RhoGEF2 regulate actin organization during cell constriction in Drosophila.

Journal Article Development · February 2007 Morphogenesis involves the interplay of different cytoskeletal regulators. Investigating how they interact during a given morphogenetic event will help us understand animal development. Studies of ventral furrow formation, a morphogenetic event during Dros ... Full text Link to item Cite

Cell adhesion: separation of p120's powers?

Journal Article Curr Biol · January 9, 2007 The catenin p120 is involved in many processes, including cell-cell adhesion and cancer. Recent work explores whether p120 independently regulates two key binding partners, RhoGTPase and cadherin. ... Full text Link to item Cite

Rho1 regulates Drosophila adherens junctions independently of p120ctn.

Journal Article Development · November 2005 During animal development, adherens junctions (AJs) maintain epithelial cell adhesion and coordinate changes in cell shape by linking the actin cytoskeletons of adjacent cells. Identifying AJ regulators and their mechanisms of action are key to understandi ... Full text Link to item Cite

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

Journal Article J Cell Biol · December 22, 2003 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 ... Full text Link to item Cite

Drosophila p120catenin plays a supporting role in cell adhesion but is not an essential adherens junction component.

Journal Article J Cell Biol · February 3, 2003 Cadherin-catenin complexes, localized to adherens junctions, are essential for cell-cell adhesion. One means of regulating adhesion is through the juxtamembrane domain of the cadherin cytoplasmic tail. This region is the binding site for p120, leading to t ... Full text Link to item Cite