Tet-On Twist: A Game-Changer in Melanoma Treatment Discovery
Presentation Type
Poster
Faculty Advisor
Carlos Molina
Access Type
Event
Start Date
26-4-2024 9:45 AM
End Date
26-4-2024 10:44 AM
Description
Skin cancer represents the most prevalent malignancy in the United States, with melanoma as its deadliest variant. Notably, melanoma can exhibit resistance to conventional treatments and affects diverse demographic groups. Consequently, extensive efforts are underway to develop effective therapies against melanoma. Zebrafish serve as a widely utilized model organism for evaluating prospective treatments. In prior studies, zebrafish genetically predisposed to melanoma development were employed to assess the efficacy of candidate treatments. However, these earlier models featured constitutive expression of protein treatments from birth, rather than initiating expression post-cancer formation. In clinical practice, treatment commencement in humans occurs subsequent to melanoma confirmation. Hence, an improved model is imperative to evaluate the effectiveness of potential tumor suppressor proteins, which should commence expression only upon melanoma incidence confirmation. Leveraging the Tet-on system, gene expression can be controlled based on the presence of the antibiotic doxycycline. A novel inducible plasmid-vector, facilitating expression modulation in melanocytes, has been created, enabling researchers to investigate their candidate genes against melanoma at any point during tumorigenesis. Experimental confirmation of inducible expression was conducted in zebrafish at 6 days post-fertilization by inducing expression of enhanced green fluorescent protein. Confirmation of expression was attained by assessing fluorescence levels in zebrafish positive for the integrated plasmid vectors, exposed to either doxycycline or doxycycline-free water. Upon reaching adulthood, modulation of expression will be confirmed via fluorescence levels once again. Following confirmed adulthood expression, this model will be released allowing for any scientist to test any gene of interest against melanoma.
Tet-On Twist: A Game-Changer in Melanoma Treatment Discovery
Skin cancer represents the most prevalent malignancy in the United States, with melanoma as its deadliest variant. Notably, melanoma can exhibit resistance to conventional treatments and affects diverse demographic groups. Consequently, extensive efforts are underway to develop effective therapies against melanoma. Zebrafish serve as a widely utilized model organism for evaluating prospective treatments. In prior studies, zebrafish genetically predisposed to melanoma development were employed to assess the efficacy of candidate treatments. However, these earlier models featured constitutive expression of protein treatments from birth, rather than initiating expression post-cancer formation. In clinical practice, treatment commencement in humans occurs subsequent to melanoma confirmation. Hence, an improved model is imperative to evaluate the effectiveness of potential tumor suppressor proteins, which should commence expression only upon melanoma incidence confirmation. Leveraging the Tet-on system, gene expression can be controlled based on the presence of the antibiotic doxycycline. A novel inducible plasmid-vector, facilitating expression modulation in melanocytes, has been created, enabling researchers to investigate their candidate genes against melanoma at any point during tumorigenesis. Experimental confirmation of inducible expression was conducted in zebrafish at 6 days post-fertilization by inducing expression of enhanced green fluorescent protein. Confirmation of expression was attained by assessing fluorescence levels in zebrafish positive for the integrated plasmid vectors, exposed to either doxycycline or doxycycline-free water. Upon reaching adulthood, modulation of expression will be confirmed via fluorescence levels once again. Following confirmed adulthood expression, this model will be released allowing for any scientist to test any gene of interest against melanoma.