Paul Kulesa, PhD, Developmental and Behavioral Health, received a $1,987,500 R01 Grant from the National Institutes of Health (NIH)’s National Institute of Neurological Disorders and Stroke (NINDS).
The grant is for Dr. Kulesa’s study “Investigating the relationship between Sympathetic Nervous System Development and Neuroblastoma” and covers a project period of August 1, 2024-April 30, 2028 (Award Number: 7R01NS128108-02).
Dr. Kulesa’s study will explore how the signals that regulate the collective movement and differentiation of neural crest cells are arranged, spatially and temporally, to assemble the sympathetic nervous system and how errors can lead to birth defects and cause the infant cancer neuroblastoma.
As Dr. Kulesa explains, a common feature of embryonic development is that cells are born in one place and have to move and regulate their differentiation before connecting with a vital target in a different location. One result of this is assembly of the sympathetic nervous system: essential for maintaining blood pressure, heart rate, and temperature control.
The study team will implement an innovative combination of techniques from dynamic, in vivo imaging and spatial transcriptomic sciences applied to the avian model system, with the advantage to incubate the egg to precise developmental time points, then visualize cell dynamics in the intact embryo.
The results of this study will advance our understanding of the cellular and molecular mechanisms of sympathetic nervous system development, with special focus on the role of the receptor tyrosine kinase receptor B, or TrkB. The Kulesa laboratory previously discovered that TrkB is upregulated by migrating neural crest cells with cells responding to brain-derived neurotrophic factor; however, it is unclear whether TrkB initiates their migration and regulates the transition of neural crest cells into sympathetic neurons. Furthermore, TrkB is highly expressed in aggressive neuroblastoma cancers but its function in disease progression remains unknown.
“We expect that the results of this study may lead to translational studies to correct by neural repair errors in neural circuit formation and inform drug design efforts targeting developmental signals, including TrkB, as a treatment for neuroblastoma,” said Dr. Kulesa.
Jennifer Kasemeier, PhD, Developmental and Behavioral Health, is a co-investigator on the study.
The contents are those of the investigator and do not necessarily represent the official views of, nor an endorsement, by NIH, or the U.S. Government.