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The Role of SoxE Transcription Factors in Neural Crest Cell Specialization

Award Number: K99DE031825
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/03/2023
PERIOD OF PERFORMANCE END DATE: 09/15/2024

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The Role of SoxE Transcription Factors in Neural Crest Cell Specialization - Project Summary/Abstract Neurocristopathies are a class of syndromes that are predominately characterized by malformations in the craniofacial complex. These defects are caused by aberrant development of the neural crest, a stem cell population unique to vertebrates. One distinctive feature of the neural crest is their ability to give rise to both ectomesenchymal (bone/cartilage) and non-ectomesenchymal (melanocytes and peripheral neurons/glia) derivatives. SoxE transcription factors play important roles in both the formation and the diversification of the neural crest. All three SoxE factors (Sox8, Sox9, and Sox10) function redundantly to promote neural crest formation. Interestingly, individual SoxE factors direct the differentiation of the neural crest into distinct lineages. Sox9 promotes chondrogenesis while Sox10 supports both the melanocyte and peripheral neuron/glial fates. An outstanding question is how these highly similar SoxE factors lead to neural crest specialization. This proposal utilizes omics-based approaches, gain and loss of function experiments, and Sox9-Sox10 chimera constructs to assess how and when SoxE-mediated neural crest specialization occurs. Furthermore, mutations in SOX9 and SOX10 are causative for Campomelic dysplasia and Waardenburg syndrome, respectively. The syndromes present with very different craniofacial phenotypes which are reflective of SOX9/SOX10 specific defects during neural crest specialization. Work from this study will lead to the identification of novel SoxE transcriptional targets, determine when SoxE factors begin to promote neural crest specialization, and determine how specific patient variants for Campomelic dysplasia/Waardenburg syndrome cause disease phenotypes. Overall, this work is of high clinical significance and will provide evolutionary insights into the molecular origins of neural crest diversification. My primary goal for the mentored phase of this proposal is to identify when SoxE factors begin to promote lineage specialization within the neural crest and determine the functional domains that contribute to SoxE family subfunctionalization. I plan to use my remaining time as a postdoctoral fellow to master new experimental techniques and develop robust computational analyses. I will capitalize on the rich academic environment of Northwestern University, especially the expertise in NSF-Simons Center for Quantitative Biology. My long-term career goal is to establish an independent research program that uses multiple model systems to investigate the cellular and molecular origins of syndromes characterized by craniofacial phenotypes. I plan to use Sox transcription factors (and associated syndromes) as a starting point in my career, but then extend my research interests to other gene families through collaboration with clinicians. My measurable experience with various model organisms will allow me to investigate biochemical, molecular, cellular, and morphological aspects of developmental disorders by exploiting the benefits of each model system.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Oral Diseases and Disorders Research	000	2	4/7/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $97,049 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Oral Diseases and Disorders Research	001	2	9/13/2024	NON-COMPETING CONTINUATION	$0
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Oral Diseases and Disorders Research	000	2	6/26/2024	NON-COMPETING CONTINUATION	$97,049
														Subtotal = $97,049

Issue Date FY: 2023 ( Subtotal = $97,049 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Oral Diseases and Disorders Research	000	1	7/3/2023	NEW	$97,049
														Subtotal = $97,049

Grand Total All Awards = $194,098

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The Role of SoxE Transcription Factors in Neural Crest Cell Specialization

Award Number: K99DE031825

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/03/2023

PERIOD OF PERFORMANCE END DATE: 09/15/2024

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