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NIH grant 1K99HD121969-01: Deciphering and manipulating the dynamic signaling and transcriptional programs of appendage regeneration
Institute: {'code': 'HD', 'abbreviation': 'NICHD', 'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development', 'admin_org_id': '12500030', 'admin_funding_url': ''}. PI: Sushant Bangru. Award: $131832.
Start: 2026-08-21T00:00:00.
ABSTRACT
The ability to regenerate complex tissues with correct size, and shape remains a central question in regenerative
biology. While mammals can regenerate bony structures in limited contexts such as digit tips, zebrafish restore
dermal appendages like scales and fins with striking precision—offering externally accessible tissues that
regenerate within days to weeks and serve as exceptional models for visualizing regenerative events. While
these models have led to tremendous gains in knowledge of core signaling pathways required for regeneration,
we still have an incomplete understanding of how spatiotemporal patterning of signaling dynamics, transcriptional
output, and physiological cues converge to control regenerative growth. A major barrier to this has been the
challenge of documenting such dynamic events in vivo at single-cell resolution, and of manipulating them with
high spatiotemporal resolution. This proposal uses an exciting multidisciplinary approach—combining live
imaging, optogenetics, and mathematical modeling—to dissect how osteoblasts within these dermal
appendages interpret dynamic signals to regenerate tissue. Recent work showed that ERK activity, during scale
and fin regeneration, is spatially patterned as traveling waves or decaying gradients, suggesting that tissue-scale
signaling dynamics can encode temporal and positional information. However, how the biophysical parameters
of these signals are modulated to accurately regenerate tissues, and how they integrate with physiological states
like ion flux and membrane potential remains unknown. In Aim 1, I will quantify ERK wave dynamics across
dermal scale regenerates of variable geometries and develop predictive models linking wave parameters to
regenerative outcomes and use in vivo optogenetic tools to test model predictions. In Aim 2, I will identify the
gene regulatory mechanisms that prime osteoblasts to respond to signaling waves and examine how signaling
wave patterns are decoded into transcriptional programs that affect bone growth. Lastly, in Aim 3, I will
quantitatively map and manipulate bioelectric cues to uncover their role in osteoblast behavior and regenerative
patterning in scales and fins. The research outlined here will form the intellectual basis of my own independent
research program. The project is supported by an interdisciplinary training plan with mentorship from Dr. Kenneth
Poss, a leader in vertebrate regeneration and zebrafish genetics, and Dr. Stefano Di Talia, an expert in
quantitative imaging and developmental modeling. Their long-standing collaboration offers a unique dual-
mentorship model across institutions, combining strength in in vivo regeneration biology with quantitative
systems-level analysis. I will receive hands-on training in optogenetic tool development, quantitative imaging,
and theoretical modeling, with guidance from an exceptional advisory committee spanning regeneration biology,
biophysics, bioelectricity, and in vivo imaging. Together, this work will uncover principles by which dynamic
signals are interpreted during vertebrate appendage regeneration and lay the foundation for an independent
future research program focused on decoding spatially patterned cues that govern tissue growth and repair.document fetched 2026-08-30 02:46