Director and Senior Scientist, Vollum Institute
Marc Freeman is director of the Vollum Institute. He earned his B.S. in Biology from Eastern Connecticut State University in 1993. He carried out his doctoral training in the laboratory of John Carlson at Yale University, where he studied Drosophila olfaction. Freeman trained as a postdoctoral associate with Chris Doe at the University of Oregon from 1999–2004, studying Drosophila embryonic neurogenesis. He started his laboratory in the Department of Neurobiology at The University of Massachusetts Medical School in 2004. Freeman was selected as a Smith Family New Investigator (2004), an Alfred P. Sloan Research Fellow (2005), and a Howard Hughes Medical Institute Early Career Scientist (2009–2013). He was an HHMI Investigator from 2013 to 2016, until he moved to the Vollum Institute in 2016.
Summary of current research
The complexity of the nervous system in even simple organisms presents neuroscientists with a number of fascinating puzzles. How are such staggeringly complex neural circuits assembled and refined? How does information flow through these networks to drive behavior? Once assembled, how is the brain supported metabolically and maintained over the lifetime of the animal? Glial cells evolved to enhance neuronal physiology, and it is now clear that glia perform a remarkably diverse array of functions that are essential for normal neural circuit assembly, function, plasticity and maintenance. In short, almost everything that neurons do in the nervous system depends on extensive cell-cell signaling between neurons and glia. Despite their importance in nearly all aspects of nervous system physiology, we understand very little about glial biology in any organism. Glial cells are also the primary responders to neuronal injury and become activated during neurodegeneration. How glia sense perturbed neural physiology remains unclear, and whether they are simply responding to or helping drive disease is an open question. Our goal is to achieve a deep mechanistic understanding of glial cell biology and neuron-glia signaling in the healthy and diseased nervous system. Our hope is that this information will help unravel fundamental principles of nervous system physiology and help determine how these processes go awry in disease.
Sambashivan S, Freeman MR. (2021) SARM1 signaling mechanisms in the injured nervous system. Curr. Opin. Neurobiol. 69:247-255.
Lin TH, Bis-Brewer DM, Sheehan AE, Townsend LN, Maddison DC, Züchner S, Smith GA, Freeman MR. (2021) TSG101 negatively regulates mitochondrial biogenesis in axons. Proc. Natl. Acad. Sci. USA 118(20):e2018770118.
Ackerman SD, Perez-Catalan NA, Freeman MR, Doe CQ. (2021) Astrocytes close a motor circuit critical period. Nature 592:414-420.
Hsu JM, Kang Y, Corty MM, Mathieson D, Peters OM, Freeman MR. (2021) Injury-induced inhibition of bystander neurons requires dSarm and signaling from glia. Neuron 109:473-487.e5.
Ma Z, Freeman MR. (2020) TrpML-mediated astrocyte microdomain Ca2+ transients regulate astrocyte-tracheal interactions. eLife 9:e58952.
Chen J, Poskanzer KE, Freeman MR, Monk KR. (2020) Live-imaging of astrocyte morphogenesis and function in zebrafish neural circuits. Nature Neurosci. 23:1297-1306.
Gu P, Gong J, Shang Y, Wang F, Ruppell KT, Ma Z, Sheehan AE, Freeman MR, Xiang Y. (2019) Polymodal nociception in Drosophila requires alternative splicing of TrpA1. Curr. Biol. 29:3961-3973.e6.
Smith GA, Lin TH, Sheehan AE, Van der Goes van Naters W, Neukomm LJ, Graves HK, Bis-Brewer DM, Züchner S, Freeman MR. (2019) Glutathione S-transferase regulates mitochondrial populations in axons through increased glutathione oxidation. Neuron 103:52-65.e6.
Cho S, Muthukumar AK, Stork T, Coutinho-Budd JC, Freeman MR. (2018) Focal adhesion molecules regulate astrocyte morphology and glutamate transporters to suppress seizure-like behavior. Proc. Natl. Acad. Sci. USA 115:11316-11321.
Peters OM, Lewis EA, Osterloh JM, Weiss A, Salameh JS, Metterville J, Brown RH, Freeman MR. (2018) Loss of Sarm1 does not suppress motor neuron degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. Hum. Mol. Genet. 27:3761-3771.
Neukomm LJ, Burdett TC, Seeds AM, Hampel S, Coutinho-Budd JC, Farley JE, Wong J, Karadeniz YB, Osterloh JM, Sheehan AE, Freeman MR. (2017) Axon death pathways converge on Axundead to promote functional and structural axon disassembly. Neuron 95:78-91.e5.
Ma Z, Stork T, Bergles DE, Freeman MR. (2016) Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour. Nature 539:428-432.
Sreedharan J, Neukomm LJ, Brown RH, Freeman MR. (2015) Age-dependent TDP-43-mediated motor neuron degeneration requires GSK3, hat-trick, and xmas-2. Curr. Biol. 25:2130-2136.
Stork T, Sheehan A, Tasdemir-Yilmaz OE, Freeman MR. (2014) Neuron-glia interactions through the Heartless FGF receptor signaling pathway mediate morphogenesis of Drosophila astrocytes. Neuron 83:388-403.
Neukomm LJ, Burdett TC, Gonzalez MA, Züchner S, Freeman MR. (2014) Rapid in vivo forward genetic approach for identifying axon death genes in Drosophila. Proc. Natl. Acad. Sci. USA 111:9965-9970.
Tasdemir-Yilmaz OE, Freeman MR. (2014) Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Genes & Dev. 28:20-33.
Osterloh JM, Yang J, Rooney TM, Fox AN, Adalbert R, Powell EH, Sheehan AE, Avery MA, Hackett R, Logan MA, MacDonald JM, Ziegenfuss JS, Milde S, Hou YJ, Nathan C, Ding A, Brown RH Jr, Conforti L, Coleman M, Tessier-Lavigne M, Züchner S, Freeman MR. (2012) dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science 337:481-484.
Avery MA, Rooney TM, Pandya JD, Wishart TM, Gillingwater TH, Geddes JW, Sullivan PG, Freeman MR. (2012) WldS prevents axon degeneration through increased mitochondrial flux and enhanced mitochondrial Ca2+ buffering. Curr. Biol. 22:596-600.
Ziegenfuss JS, Biswas R, Avery MA, Hong K, Sheehan AE, Yeung YG, Stanley ER, Freeman MR. (2008) Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature 453:935-939.
MacDonald JM, Beach MG, Porpiglia E, Sheehan AE, Watts RJ, Freeman MR. (2006) The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 50:869-881.