PROJECT SUMMARY
The long-term objective of this project is to determine the general principles and causal mechanisms
underlying subcellular RNA localization, and the physiological implications during development and disease. In
particular, the subcellular localization of messenger RNA (mRNA) to cell protrusions is known to be required
for cell migration, but the mechanisms by which mRNA localization regulates protein function in this setting are
unclear. Many genes implicated in mRNA localization are expressed in neural crest cells, which are
a particularly migratory cell type that gives rise to much of the vertebrate head, as well as neurons,
melanocytes, and aggressive cancers including melanoma. As such, neural crest cells provide a rich
environment to uncover molecular mechanisms of mRNA localization in cell migration as well as the relevance
there of to mammalian physiology. In this project, I will use cultured melanoma cells to identify and
characterize trans-acting regulators of mRNA localization and elucidate the role of mRNA localization on
protein function. I will also use in vivo mouse models to catalog mRNA localization that occurs during neural
crest cell development and directly test the role of a well characterized localized mRNA, Kif1c, during
development and cancer onset and progression. As neural crest and cancer genetics fields rely heavily on
transcriptional studies, the mechanistic understanding of a post-transcriptional process as described here may
provide unique insight into the cause, diagnosis and treatment of craniofacial birth defects and melanoma
onset and progression.
My career goal is to run an academic research program analyzing the role and regulation of subcellular RNA
localization during embryogenesis, with special attention to neural crest cells and their derivatives. My ambition
is to have a lab that can determine molecular mechanisms at the single-molecule level and causally link those
processes to physiological outcomes in vivo. To this end, the proposed experiments and training plan are
designed to develop expertise in cutting-edge technologies such as TIRF microscopy, computational image
analysis, genetic engineering and in vivo disease assays. Training in these advanced techniques will be
directly supported by the resource-rich and collaborative environment at UT Southwestern, and especially
mentorship from Dr. Gaudenz Danuser, Dr. Ondine Cleaver, Dr. Khuloud Jaqaman, Dr. Lu Le and Dr. Sean
Morrison, who make up my advisory committee. The Pathway to Independence Award will provide the time,
resources and autonomy to fully develop and initiate this ambitious research program and accrue the
resources, expertise and experience necessary to launch an impactful, thriving research lab in Fall 2024.