Kelly Monk, Ph.D.
Kelly Monk is a senior scientist and co-director of the Vollum Institute. After earning her B.S. degree in Biochemistry from Elmira College in 2001, Monk pursued doctoral studies at the University of Cincinnati under the mentorship of Nancy Ratner and was awarded her Ph.D. in Cell Biology in 2006. She did postdoctoral training in the lab of William Talbot at Stanford University School of Medicine. In 2011, she was appointed as an assistant professor in the Department of Developmental Biology at Washington University School of Medicine in St. Louis, and was promoted to associate professor in 2016. Monk joined the Vollum Institute in 2017.
Summary of Current Research
The myelin sheath surrounding axons is one of the most exquisite examples of a specialized cell-cell interaction in the vertebrate nervous system. Myelin is formed by glial cells called oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. These cells associate with axons, and elaborate massive amounts of cytoplasm, ultimately wrapping axons to form the myelin sheath. While progress has been made to determine how glial cells make myelin, there is still much we do not understand.
How do glial cells transition from simple axonal ensheathment to membrane spiraling? What are the signals between glial cells and axons that regulate myelination? How is myelin maintained once it is formed? When myelin regenerates in disease or after injury, do the same developmental pathways that regulate myelination regulate remyelination? Or are there additional pathways necessary for this process, specific to adult tissue?
We use mouse and zebrafish models to better understand how myelinated axons are formed, maintained, and regenerated.
Current Projects in the Lab
A specific focus of our studies is to understand how adhesion G protein-coupled receptors (aGPCRs) control Schwann cell and oligodendrocyte development, myelination, and remyelination. We defined aGPCRs as key regulators of both PNS and CNS myelination by demonstrating that the aGPCR GPR126 is required in Schwann cells for many stages of Schwann cell development, while the aGPCR GPR56 controls oligodendrocyte precursor proliferation. Our work has also defined new ligands for GPR126 and activation paradigms for the aGPCR class. We are currently working to dissect the mechanisms by which GPR126 and GPR56 control myelinating glial cell development and myelin repair using zebrafish and mouse models.
Beyond GPR126 and GPR56, there are 31 other aGPCRs in the human genome—we are working to define the aGPCR repertoire required in myelinating glia during development and repair, how these aGPCRs are activated and how they signal in glia, and whether we can target aGPCRs to promote remyelination.
Myelin is an evolutionary innovation of vertebrates; thus, zebrafish represents the simplest model system to elucidate the genetic and molecular mechanisms that regulate myelination. We recently completed a large-scale forward genetic screen and uncovered 28 new mutants with myelin defects in both the CNS and PNS. We are currently working to determine how these genes function in Schwann cells and oligodendrocytes using zebrafish and mouse models, and we expect that these studies will enhance our understanding of these critically important cells while pointing the way to novel therapeutics to promote regeneration in the nervous system.
In other studies, we are pursuing modifier screens to search in an unbiased way for modulators of GPR126 activity. We are performing small molecule and genetic screens to find compounds and mutations that can enhance or suppress hypomorphic gpr126 mutant phenotypes.
Herbert AL, Fu MM, Drerup CM, Gray RS, Harty BL, Ackerman SD, O'Reilly-Pol T, Johnson SL, Nechiporuk AV, Barres BA, Monk KR. (2017) Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo. Proc. Natl. Acad. Sci. USA 114:E9153-E9162.
Sanchez NE, Harty BL, O'Reilly-Pol T, Ackerman SD, Herbert AL, Holmgren M, Johnson SL, Gray RS, Monk KR. (2017) Whole genome sequencing-based mapping and candidate identification of mutations from fixed zebrafish tissue. G3: Genes, Genomes, Genetics 7:3415-3425.
Mogha A, Harty BL, Carlin D, Joseph J, Sanchez NE, Suter U, Piao X, Cavalli V, Monk KR. (2016) Gpr126/Adgrg6 has Schwann cell autonomous and nonautonomous functions in peripheral nerve injury and repair. J. Neurosci. 36:12351-12367.
Petersen SC, Luo R, Liebscher I, Giera S, Jeong SJ, Mogha A, Ghidinelli M, Feltri ML, Schöneberg T, Piao X, Monk KR. (2015) The adhesion GPCR GPR126 has distinct, domain-dependent functions in Schwann cell development mediated by interaction with Laminin-211. Neuron 85:755-769.
Ackerman SD, Garcia C, Piao X, Gutmann DH, Monk KR (2015) The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA. Nature Commun. 6:6122.