Dr. Don Fox joins the Board of Scientific Advisors
Dr. Don Fox has joined the Jane Coffin Childs Fund for Medical Research as a Scientific Advisor. Dr. Fox is a Professor in the Department of Pharmacology & Cancer Biology and the Department of Cell Biology at Duke University School of Medicine. Research in the Fox Lab is focused on the role of both DNA polyploidy and RNA codon usage in organ development and regeneration.
Dr. Don Fox
Scientific Training
A developmental biologist at heart, Fox studied the role of cytoskeleton regulators in animal development spanning the molecular, cellular, and tissue scales as a PhD student in Dr. Mark Peifer’s Lab at the University of North Carolina. Fox clarified the mechanisms of known cytoskeleton regulators, and identified novel regulators of ventral furrow formation – a morphogenetic event early in Drosophila development.
Next, Fox joined Dr. Allan Spradling’s Lab at the Carnegie Institution of Washington to work on an interesting project in organ development and regeneration. During the pupal stage of fruit fly development, all of the organs – with the exception of the brain – are destroyed and remade. How exactly this process works had been a longstanding question as the destruction and regeneration of new organs was originally described in the 1930s.
Fox discovered that the adult Drosophila hindgut is not generated by active stem cells. Rather, the process of tissue damage elicits an unexpected cell regeneration program. cell proliferation from quiescent stem cells. Specifically, Fox uncovered a role for polyploidy – additional copies of genomic DNA – in the tissue regeneration process.
During hindgut development, Fox also discovered another new way that polyploidy can build or re-build tissues. During the process by which the pupa re-makes its hindgut during the conversion from larva to fly, Fox found that some polyploid hindgut cells in the rectal region re-enter the mitotic cell cycle. Polyploid cell division is frequently observed in cancer cells, but less is known about potential roles during normal development and homeostasis. Fox’s findings indicated that these polyploid rectal cells may provide an accessible model to study links between division of polyploid cells and genome integrity.
Example of 8N polyploid (left) and 2N diploid (right/inset) Drosophila pupal rectal cells from Fox et al, 2010.
Fox Lab
In his own lab at Duke Fox has continued to examine the importance of polyploidy in tissue regeneration. Fox notes that polyploidy is a handy way to regenerate lost tissue mass. In situations where new cells are not made, polyploidy allows the remaining cells in that tissue to fill the gap, so to speak. Also, Fox and his lab have found that polyploid cells appear to have a distinct set of rules that govern their cell division as compared to diploid cells. While these different rules are often viewed as mistakes, particularly in the realm of cancer, Fox thinks that these rules may offer a unique window into the functions that polyploid cells carry out during normal development and homeostasis.
Recently, Fox helped establish the Polyploidy Integration and Innovation Institute – an exciting new NSF-funded initiative that will examine polyploidy across the tree of life. His lab will bring their expertise in fruit flies and collaborate with other scientists who study polyploidy in plants, algae, and fungi. The initiative hopes to piece together a broader view of polyploidy, with potential applications in medicine, agriculture, and conservation.
Fox’s lab has also become interested in how developing tissues each rely on a preferred set of codons, the genetic instructions needed to specify amino acids in proteins. In contrast to the view that each organism contains an “optimal” set of codons, Fox’s group are finding that codon optimality depends largely on the cell and tissue context. For example, they recently found that a larval brain stem cell differs significantly from a neuron in terms of preferred codons, and that altering codons can have profound impacts on animal behavior.
Illustrative size difference between diploid and polyploid cells and organism from Morris et al, 2024.
JCC
As a former JCC Fellow, Fox recalls the boost that receiving this award had on his scientific development, and fondly remembers JCC annual meetings discussing science with giants such as Drs Joan Steitz and Randy Schekman. Now as an BSA member, Fox looks forward to being a part of that experience for current and future Fellows.
He advises JCC Fellows to go for it! Early in your postdoc is the perfect time to try that big project that has the potential to be a game changer and serve as a foundation for a long-lasting career. Welcome to the JCC BSA, Dr. Fox!