Below is the list of the ongoing research projects in the lab. Our work focuses on studying mechanisms of regeneration and development, as well as on developing research tools.
Nerve dependency of regeneration
Mechanobiology of joint development
Limb development and patterning
Epithelium in limb regeneration
Development of optical nanosensors
Nerve dependency of regeneration
Regeneration requires innervation. Nerves release molecules that encourage cell division and repair of injured organs and tissues. We have discovered that one such nerve-derived molecule is neuregulin-1, which drives regeneration of the axolotl limbs, spinal cord, and lungs. Many current lab projects target the role of nerves in limb regeneration, including regulation of cell cycle and timeline of regeneration.
Funding source: National Science Foundation
Mechanobiology of joint morphogenesis
Axolotls are a useful model for studying how joints assume their complex shapes. In collaboration with the Shefelbine lab, we combine research on developing and regenerating axolotl limbs with predictive computational models to understand how mechanical forces trigger cellular signaling responses and change joint shape.
Funding source: National Science Foundation
V3 HCR FISH in regeneration
We have developed the application of V3 HCR FISH (Version 3 Hybridization Chain Reaction Fluorescent In Situ Hybridization) to axolotl tissues. This innovative technique detects cells that express particular genes, and it also shows where these cells are located in organs and tissues. Our lab employs this technique to uncover cellular and molecular mechanisms in regeneration.
Limb development and patterning
A developing or regenerating limb must grow bones, muscles, nerves, and skin – all in right amounts and places. This process of limb patterning is regulated by many signaling molecules. Retinoic acid, a metabolite of vitamin A, is one of them. We use V3 HCR FISH and a genetic engineering tool CRISPR/Cas9 to understand how retinoic acid controls axolotl limb growth. We also compare gene expression during regeneration and development to understand the mechanisms of limb growth.
Funding source: National Institutes of Health
Hypertranscription
We have observed that some axolotl neural stem cells produce much more RNA than others. This elevated amount of gene expression is called hypertranscription. We research how hypertranscribing neural stem cells contribute to adult neurogenesis and potentially to brain repair.
Epithelium in limb regeneration
Shortly after axolotl limb amputation, skin cells migrate and cover the open wound. This wound epithelium then forms the apical epithelial cap on the tip of the blastema, which is critical for limb regeneration. We study gene expression in the skin of regenerating limbs, with special attention to how Wnt5a determines the direction of limb outgrowth.
Funding source: National Science Foundation
Development of optical nanosensors for imaging of neurotransmitter release
In collaboration with the Clark Laboratory, we are developing novel nanosensors to image neurotransmitter release in living mice. This nanosensor development project is part of an NIH Initiative to Stimulate Peripheral Activity to Relieve Conditions (SPARC).
Funding source: National Institutes of Health
Retinal regeneration
Retina is a thin neural structure in the eye that captures visual information about the world and sends it to the brain. Unlike humans, axolotls can regenerate their damaged retinas, regrowing the neurons and nerve connections. In collaboration with the Carrier laboratory, we investigate what genes and cells drive axolotl retinal regeneration.
Funding sources: National Science Foundation, Retina Research Foundation