MDI Biological Laboratory
Assistant Professor

Prayag Murawala, Ph.D.

What makes axolotls regenerate and what blocks regeneration in us?

The Murawala Lab combines diverse disciplines (developmental biology, evolutionary biology, epigenetics, genomics and biophysics) and next-generation technologies such as gene manipulations, whole body imaging, and single cell -omics to understand the mechanisms of complex tissue regeneration.

The axolotl is a robust model of tissue regeneration because it can regenerate many different body parts, including limbs, tail, heart and even the brain. Their body is partially transparent, allowing scientists to visualize internal organs while they are developing and regenerating. On a phylogenetic tree, the axolotl is seated in between the zebrafish and the mouse (the two most studied vertebrates), which provides us with a crucial reference for evolutionary studies.

Research

Limb regeneration

The limb is a complex structure that consists of numerous tissue types such as epidermis, bones, muscles, fibroblasts, nerves, vasculature and immune cells. Upon limb amputation all these cell types coordinate with each other and carry out an extraordinary feat of restoring exactly the lost portion. How do the cells even know where the amputation was made? How do they know when to stop regenerating? How do they form an exact replica with all the proper skeletal elements? These are just some of the questions that keep the Murawala Lab busy.

Tail regeneration

The axolotl is one of few organisms that can regenerate its primary body axis, including the spinal cord. During embryonic development, an array of myotomes and vertebrae is formed through a segmentation process called somitogenesis. Upon tail amputation axolotls also recreate new segments, each containing new muscles and vertebrae. However, these segments originate from a mature tissue and in the absence of somites. Using state of the art technologies, the Murawala Lab is addressing questions such as: what is the cellular source of the tail blastema and what are the underlying molecular mechanisms of tail regeneration.

Tissue metamorphosis

Axolotls are full of wonder. Although they spend most of their life in neoteny, in the lab they are capable of metamorphosis. A single exposure to L-thyroxine transforms axolotl body – they retract their gills and start breathing with their lungs. During metamorphosis they shed their skin and the emerging skin is more compatible with the terrestrial habitat. They lose their fin and their tail rounds up. Interestingly, they can still display tissue regeneration ability, although there is a small decline in the rate and fidelity. The Murawala Lab wants to understand cellular and molecular basis for metamorphosis and its implication on tissue regeneration.

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Lab Members

Karen Crawford, Ph.D.Senior Research Scientist

Dr. Crawford, Ph.D. is a Senior Research Scientist and Professor Emerita at St. Mary’s College of Maryland. In the Murawala laboratory, she studies and assists with the study of embryogenesis, regeneration and metamorphosis in the axolotl. Her work blends classic surgical methods and precision microinjection with cutting edge molecular methods to elucidate the mechanisms of pattern formation in development and regeneration. Her research interests and contributions span embryogenesis and regeneration studies in vertebrates (salamander and chick) and invertebrates (worm and squid) and includes seminal genome editing studies in cephalopods.

Roberto Damián García-GarcíaPh.D. Candidate, Hannover Biomedical Research School

Damian holds a Bachelor’s degree in Basic Biomedical Research and a Master’s in Biochemical Sciences with a specialization in Developmental Biology, both from the National Autonomous University of Mexico (UNAM). Currently, Damián is pursuing a Ph.D. degree in the Murawala Lab, focussing on developing novel tools to study the intercellular communication during limb regeneration, particularly in relation to the regulation of progenitor cell’s proliferation, differentiation, and organization.

Vijayishwer Singh JamwalGraduate Student, University of Maine GSBSE

Vijayishwer Singh Jamwal completed a Bachelor’s degree in Life Sciences and a Master’s degree in Zoology with a specialization in Fisheries and Aquaculture. Jamwal joined the Centre for Cellular and Molecular Biology (CCMB), working on tissue engineering using induced pluripotent stem cells and collagen–Gum Arabica hydrogels to develop biocompatible scaffolds for cartilage regeneration in rats. Jamwal joined the Murawala Lab, to study muscle development and repair in Ambystoma mexicanum (axolotl), currently focusing on understanding the dynamics of Muscle progenitors in volumetric muscle loss (VML) repair across both the primary and secondary body axes, and extracellular matrix (ECM) remodeling during repair.

Omar MagedGraduate student, Regenerative Sciences, Hannover Biomedical Research School (HBRS)

Omar Maged got a B.Sc. in Biotechnology from Cairo University, Egypt in 2018, where his graduation project was focused on the isolation and transdifferentiation of adipose derived stem cells. It was then that he developed an interest in stem cells and regenerative medicine. Maged received a M.Sc. in Regenerative Medicine from University Malaya, Malaysia in 2023, where he studied the effects of mesenchymal stem cells-derived exosomes on diabetic tendons. Maged is currently enrolled in the Ph.D. program “Regenerative Sciences” at the Hannover Medical School (Medizinische Hochschule Hannover — MHH). He joined the Murawala Lab for my Ph.D. project, which will be centered around understanding the mechanisms of kidney regeneration in axolotl.

Samantha RathbunGraduate Student, University of Maine

Samantha Rathbun holds a Bachelor’s degree in Biology from the University of Massachusetts Boston (UMB) where she investigated the changes in DNA methylation during limb regeneration in the Mexican Axolotl in the laboratory of Dr. Catherine McCusker. She later joined the ENGAGE-Bio Post-Baccalaureate program at the Marine Biological Laboratory (MBL), Woods Hole, working in the laboratory of Dr. Andrew Gilis to understand the development and resolve the embryonic origin of Neuroendocrine Merkel cells in the little skate. Rathbun then joined the laboratory of Dr. Jessica Lehoczky at Harvard Medical School and Mass General Brigham Hospital where she aimed to evaluate how the digit tip blastema organizes and patterns into regenerated tissue. Here she developed an innovative technique to 3D culture living blastemas in vitro while preserving tissue structure and morphology. She is now pursuing her Ph.D. in the Murawala laboratory through the Graduate School of Biomedical Science and Engineering at the University of Maine. Her thesis work primarily focuses on understanding the role of thyroid hormone-induced metamorphosis in axolotl limb regeneration.

Katelyn WhiteResearch Assistant II

Katelyn White received a Bachelor of Science’s degree in Biology with a specialization in Biochemistry from Husson University in Bangor, Maine. White is a Research Assistant II in the Murawala Lab, focussing on maintaining our axolotl colony through breeding and transgenesis.

Erik FiguraCand. Medical Doctor, Hannover Medical School, Germany

Erik Figura is a medical student at the Hannover Medical School (MHH), Germany. Currently, he is part of the Hinze Lab at the Department of Nephrology and Hypertension (MHH). Figura is interested in the effect of metamorphosis on kidney function. He is visiting MDI Bio Lab for a year as a medical intern as part of a joint project between the Hinze and Murawala Lab. In this collaborative project, Figura will study the changes associated with metamorphosis in neotenic and metamorphic kidney using modern molecular biology, physiology and histological tools.