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The role of neural crest regeneration in the severity of congenital birth defects

Award Number: K99HD120625
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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The role of neural crest regeneration in the severity of congenital birth defects - PROJECT SUMMARY The neural crest (NC) is a multipotent, highly migratory, embryonic stem cell population that contributes to numerous cell types along the body axis, including the craniofacial skeleton, peripheral ganglia, melanocytes and smooth muscle of the cardiac outflow tract. Abnormal neural crest development results in some of the most common congenital birth defects affecting live born infants such as ‘Treacher Collins syndrome’ and ‘common arterial trunk’. Experimentally this is clearly demonstrated by surgical ablation of the cranial NC in chick embryos, which results in defects such as loss of facial skeleton, and through ablation of the cardiac NC, which results in defects in outflow tract septation, both highly reminiscent of human congenital birth defects. Here, I will test the hypothesis that cranial and cardiac NC forming regions can regenerate for a critical period during development, rescuing migratory NC cells, but that this ability is lost in more mature NC. I hypothesize that non-regenerative NC regions can gain regenerative ability by manipulation of key transcription factors and that gain of regenerative NC ability reduces the severity of subsequent NC-derived birth defects. To test this, I propose to combine classical and molecular approaches in the chick model to explore the role of NC regeneration in the type, incidence and severity of congenital birth defects along the body axis. To this end, the specific aims will: 1. Resolve the extent and timing of cranial neural crest regenerative ability. 2. Identify molecular mechanisms underlying NC regeneration. 3. Compare effects of NC regeneration along the body axis. The proposed research holds the promise of revealing transcriptional differences that facilitate regeneration of NC across different axial levels (cranial, cardiac and trunk). It will also reveal how loss or gain of such regenerative properties may affect the severity of congenital birth defects following NC ablation. Thus, the results may inform upon potential therapeutic implications of acquired NC regeneration in crest-derived congenital birth defects. Candidate Career Development and Goals: My ultimate long-term goal is to establish an independent research group to investigate how cell dynamics shape the embryo during development, and how dysregulation of such processes leads to developmental defects. I am particularly keen to achieve this by integrating the research skills I learn and develop during the mentored phase of the award (genomics, bioinformatics, imaging) with my existing experience (e.g. classical embryology, molecular biology). I will also continue to develop skills required to be a successful independent researcher by attending career development courses (Caltech), advancing science communication skills (meetings, publications, writing course) and mentoring and teaching skills (lecture and lab).


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: 2026 ( Subtotal = $128,331 )
2026	2026	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	8/19/2026	NEW	$128,331
														Subtotal = $128,331

Grand Total All Awards = $128,331

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The role of neural crest regeneration in the severity of congenital birth defects

Award Number: K99HD120625

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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