Although we consider our sense of taste to be constant over time, the cells that transduce taste stimuli, i.e., sweet, sour, salt, savory and bitter, are rapidly and reliably renewed from adjacent progenitor/stem cells.
Working primarily with mice, we use molecular genetic tools, combined with immunofluorescence and in situ hybridization, molecular biology assays, confocal imaging, and behavioral testing to explore taste bud development in embryos and renewal in adults.
Working primarily with mice, we use molecular genetic tools, combined with immunofluorescence and in situ hybridization, molecular biology assays, confocal imaging, and behavioral testing to explore taste bud development in embryos and renewal in adults.
Regulation of taste cell renewal
We have shown that both Wnt and Hedgehog (Hh) pathways are key regulators of taste bud homeostasis, regulating progenitor proliferation and cell fate decisions, and taste cell differentiation, respectively. We have recently shown that the SRY-box transcription factor, SOX2, which is expressed in lingual progenitors, functions downstream of Hh to promote taste cell differentiation. We are now using bulk and single cell RNAseq to identify additional regulators of taste homeostasis downstream of Hh.
We have shown that both Wnt and Hedgehog (Hh) pathways are key regulators of taste bud homeostasis, regulating progenitor proliferation and cell fate decisions, and taste cell differentiation, respectively. We have recently shown that the SRY-box transcription factor, SOX2, which is expressed in lingual progenitors, functions downstream of Hh to promote taste cell differentiation. We are now using bulk and single cell RNAseq to identify additional regulators of taste homeostasis downstream of Hh.
Investigating how cancer therapies affect taste cell renewal
A host of cancer therapies, ranging from chemotherapeutics that inhibit crucial albeit broad cellular functions, to drugs that target specific molecular pathways mutated in cancers, as well as radiotherapy for treatment of head and neck tumors, affect taste cell renewal. We have developed mouse models of conventional cancer therapies that result in taste dysfunction in patients, including: (1) head and neck irradiation; and (2) Hedgehog pathway-targeted drug treatment for basal cell carcinoma (skin cancer). We hope to develop interventions to rescue taste loss in mice following these treatments to ultimately help patients.
A host of cancer therapies, ranging from chemotherapeutics that inhibit crucial albeit broad cellular functions, to drugs that target specific molecular pathways mutated in cancers, as well as radiotherapy for treatment of head and neck tumors, affect taste cell renewal. We have developed mouse models of conventional cancer therapies that result in taste dysfunction in patients, including: (1) head and neck irradiation; and (2) Hedgehog pathway-targeted drug treatment for basal cell carcinoma (skin cancer). We hope to develop interventions to rescue taste loss in mice following these treatments to ultimately help patients.
Modeling taste cell renewal in lingual organoids.
Organoids derived from isolated adult taste stem cells produce all taste bud cell types, including those that detect sweet, bitter, umami, salty and sour. These organoids can be passaged and expanded, and give us a new tool to rapidly test candidate genes, signaling pathways, and cancer drugs for roles in regulating lingual stem cell proliferation and survival, as well as taste cell fate selection and differentiation.
We have recently been awarded an R21 grant from the NIDCD to rapidly assess how taste distorting cancer drugs used to treat patients with malignant renal cell carcinoma affect taste bud renewal at the cellular and molecular levels.
Organoids derived from isolated adult taste stem cells produce all taste bud cell types, including those that detect sweet, bitter, umami, salty and sour. These organoids can be passaged and expanded, and give us a new tool to rapidly test candidate genes, signaling pathways, and cancer drugs for roles in regulating lingual stem cell proliferation and survival, as well as taste cell fate selection and differentiation.
We have recently been awarded an R21 grant from the NIDCD to rapidly assess how taste distorting cancer drugs used to treat patients with malignant renal cell carcinoma affect taste bud renewal at the cellular and molecular levels.
The Embryo-to-Adult Transition; from specification to regeneration.
Taste bud primordia are established by mid-gestation in mice, but taste cell differentiation does not begin until birth. While the first taste cells differentiate directly from embryonically specified primordia after birth, taste stem cells adjacent to buds activate and begin to contribute new cells to postnatal taste buds. This marks the advent of taste cell renewal, a process that continues throughout life. We are investigating how this transition is regulated.
Taste bud primordia are established by mid-gestation in mice, but taste cell differentiation does not begin until birth. While the first taste cells differentiate directly from embryonically specified primordia after birth, taste stem cells adjacent to buds activate and begin to contribute new cells to postnatal taste buds. This marks the advent of taste cell renewal, a process that continues throughout life. We are investigating how this transition is regulated.
