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CC BY V4.0, Open Access
Dissertation
Dynamic Interaction Between Circadian Clock and Melanocyte Biology
Washington State University
Doctor of Philosophy (PhD), Washington State University
2021
DOI:
https://doi.org/10.7273/000005524
Abstract
Most living organisms on Earth are photosensitive, including humans, and they get influenced by the solar day and night cycles created by the axial rotation of the Earth. The diurnal exposure of ultraviolet radiation (UVR) from the Sun is responsible for various skin-related diseases, including melanoma and non-melanoma skin cancers in humans. Evolutionarily, our skin has developed various protective biological mechanisms against the harmful effects of UVR, including nucleotide excision repair (NER) and melanin. In the past, the circadian clock has been shown to regulate NER and cell cycle processes, where their ability to protect from UVR changes according to the time of the day. However, the growing trend of erratic work schedule and feeding behavior has been shown to profoundly affect our circadian clock, making our body vulnerable to a host of environmental stressors, including UVR. Similar to NER, melanin, which is synthesized in melanocytes, is regarded as one of the most effective skin protectants against UVR damage, as it absorbs excess solar UVR and protects against genomic insults. Over the years, multiple signaling pathways have been shown to influence melanin biosynthesis by directly controlling the expression on a master regulator of melanogenesis, the microphthalmia-associated transcription factor (MITF). MITF is a basic helix-loop-helix melanoma proto-oncogene known to modulate critical melanocyte mechanisms by transcriptionally controlling MITF’s target genes. As the role of the transcriptional influence of the skin circadian clock on DNA repair in protecting the cells from environmental genotoxic stress is well established, what remains unknown is its connection with melanin pigmentation through MITF and a possible feedback loop that has the potential to affect the circadian clock back. Therefore, my thesis tries to understand both the clock's properties in melanocytes and their role in protecting against the solar UVR through MITF and how clock disruption mediated by MITF contributes to melanoma initiation/progression.
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Details
- Title
- Dynamic Interaction Between Circadian Clock and Melanocyte Biology
- Creators
- Soumyadeep Sarkar
- Contributors
- Shobhan Gaddameedhi (Chair)K. Michael Dr. Gibson (Committee Member)Salah-Uddin Dr. Ahmed (Committee Member)Weimin Dr. Li (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Pharmacy and Pharmaceutical Sciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 148
- Identifiers
- 99901051540301842
- Language
- English
- Resource Type
- Dissertation