Michael Sofroniew, M.D., Ph.D.

Research

Our work is directed at achieving a better understanding of the cell biology of the response to injury in the adult central nervous system. We are particularly interested in the roles played by specific cell types (e.g. astroglia) and specific molecules (e.g. growth factors and cytokines) in mediating neuroprotection, regulating inflammation and determining the capacity for regeneration. Our studies are based largely on systems-level analysis in transgenic mouse models. Specific techniques employed include microsurgery, tissue culture, grafting (also from precursor cells and genetically modified cells), immunohistochemistry, tract-tracing, quantitative morphometry, and various molecular biological techniques associated with generating, maintaining, and evaluating transgenic mice.

Publications

Anderson Mark A, Burda Joshua E, Ren Yilong, Ao Yan, O’Shea Timothy M, Kawaguchi Riki, Coppola Giovanni, Khakh Baljit S, Deming Timothy J, Sofroniew Michael V Astrocyte scar formation aids central nervous system axon regeneration Nature, 2016; 532(7598): 195-200.

Khakh Baljit S, Sofroniew Michael V Diversity of astrocyte functions and phenotypes in neural circuits Nature neuroscience, 2015; 18(7): 942-52. Sofroniew Michael V Astrocyte barriers to neurotoxic inflammation Nature reviews. Neuroscience, 2015; 16(5): 249-63.

Tong Xiaoping, Ao Yan, Faas Guido C, Nwaobi Sinifunanya E, Xu Ji, Haustein Martin D, Anderson Mark A, Mody Istvan, Olsen Michelle L, Sofroniew Michael V, Khakh Baljit S Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice Nature neuroscience, 2014; 17(5): 694-703.

Burda Joshua E, Sofroniew Michael V Reactive gliosis and the multicellular response to CNS damage and disease Neuron, 2014; 81(2): 229-48.

Shigetomi Eiji, Bushong Eric A, Haustein Martin D, Tong Xiaoping, Jackson-Weaver Olan, Kracun Sebastian, Xu Ji, Sofroniew Michael V, Ellisman Mark H, Khakh Baljit S Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses The Journal of general physiology, 2013; 141(5): 633-47.

Song Bingbing, Song Jinsuk, Zhang Shanshan, Anderson Mark A, Ao Yan, Yang Chu-Ya, Deming Timothy J, Sofroniew Michael V Sustained local delivery of bioactive nerve growth factor in the central nervous system via tunable diblock copolypeptide hydrogel depots Biomaterials, 2012; 33(35): 9105-16.

Nobuta Hiroko, Ghiani Cristina A, Paez Pablo M, Spreuer Vilma, Dong Hongmei, Korsak Rose A, Manukyan Armine, Li Jiaxi, Vinters Harry V, Huang Eric J, Rowitch David H, Sofroniew Michael V, Campagnoni Anthony T, de Vellis Jean, Waschek James A STAT3-mediated astrogliosis protects myelin development in neonatal brain injury Annals of neurology, 2012; 72(5): 750-65.

Hamby Mary E, Coppola Giovanni, Ao Yan, Geschwind Daniel H, Khakh Baljit S, Sofroniew Michael V Inflammatory mediators alter the astrocyte transcriptome and calcium signaling elicited by multiple G-protein-coupled receptors The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(42): 14489-510.

Argaw Azeb Tadesse, Asp Linnea, Zhang Jingya, Navrazhina Kristina, Pham Trinh, Mariani John N, Mahase Sean, Dutta Dipankar J, Seto Jeremy, Kramer Elisabeth G, Ferrara Napoleone, Sofroniew Michael V, John Gareth R Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease The Journal of clinical investigation, 2012; 122(7): 2454-68.

Cushman Jesse D, Maldonado Jose, Kwon Eunice E, Garcia A Denise, Fan Guoping, Imura Tetsuya, Sofroniew Michael V, Fanselow Michael S Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories Frontiers in behavioral neuroscience, 2012; 6(3): 3.

Verkhratsky Alexei, Sofroniew Michael V, Messing Albee, deLanerolle Nihal C, Rempe David, Rodríguez José Julio, Nedergaard Maiken Neurological diseases as primary gliopathies: a reassessment of neurocentrism ASN neuro, 2012; 4(3): .

Sofroniew Michael V Transgenic techniques for cell ablation or molecular deletion to investigate functions of astrocytes and other GFAP-expressing cell types Methods in molecular biology (Clifton, N.J.), 2012; 814(3): 531-44.

Tao Jifang, Wu Hao, Lin Quan, Wei Weizheng, Lu Xiao-Hong, Cantle Jeffrey P, Ao Yan, Olsen Richard W, Yang X William, Mody Istvan, Sofroniew Michael V, Sun Yi E Deletion of astroglial Dicer causes non-cell-autonomous neuronal dysfunction and degeneration The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(22): 8306-19.

Wang Xiaohong, Imura Tetsuya, Sofroniew Michael V, Fushiki Shinji Loss of adenomatous polyposis coli in Bergmann glia disrupts their unique architecture and leads to cell nonautonomous neurodegeneration of cerebellar Purkinje neurons Glia, 2011; 59(6): 857-68.

Spence Rory D, Hamby Mary E, Umeda Elizabeth, Itoh Noriko, Du Sienmi, Wisdom Amy J, Cao Yuan, Bondar Galyna, Lam Jeannie, Ao Yan, Sandoval Francisco, Suriany Silvie, Sofroniew Michael V, Voskuhl Rhonda R Neuroprotection mediated through estrogen receptor-alpha in astrocytes Proceedings of the National Academy of Sciences of the United States of America, 2011; 108(21): 8867-72.

Sofroniew Michael V Neuromyelitis optica: circulating autoantibodies provoke astrocyte-mediated neural dysfunction Neurology, 2011; 76(14): 1202-3.

Imura Tetsuya, Wang Xiaohong, Noda Tetsuo, Sofroniew Michael V, Fushiki Shinji Adenomatous polyposis coli is essential for both neuronal differentiation and maintenance of adult neural stem cells in subventricular zone and hippocampus Stem cells (Dayton, Ohio), 2010; 28(11): 2053-64.

Crawford Daniel K, Mangiardi Mario, Song Bingbing, Patel Rhusheet, Du Sienmi, Sofroniew Michael V, Voskuhl Rhonda R, Tiwari-Woodruff Seema K Oestrogen receptor beta ligand: a novel treatment to enhance endogenous functional remyelination Brain : a journal of neurology, 2010; 133(10): 2999-3016.

Hamby Mary E, Sofroniew Michael V Reactive astrocytes as therapeutic targets for CNS disorders Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2010; 7(4): 494-506.

Shigetomi Eiji, Kracun Sebastian, Sofroniew Michael V, Khakh Baljit S A genetically targeted optical sensor to monitor calcium signals in astrocyte processes Nature neuroscience, 2010; 13(6): 759-66.

Sarafian Theodore A, Montes Cindy, Imura Tetsuya, Qi Jingwei, Coppola Giovanni, Geschwind Daniel H, Sofroniew Michael V Disruption of astrocyte STAT3 signaling decreases mitochondrial function and increases oxidative stress in vitro PloS one, 2010; 5(3): e9532.

Sofroniew Michael V, Vinters Harry V Astrocytes: biology and pathology Acta neuropathologica, 2010; 119(1): 7-35. Sofroniew Michael V Molecular dissection of reactive astrogliosis and glial scar formation Trends in neurosciences, 2009; 32(12): 638-47.

Gregorian Caroline, Nakashima Jonathan, Dry Sarah M, Nghiemphu P Leia, Smith Kate Barzan, Ao Yan, Dang Julie, Lawson Gregory, Mellinghoff Ingo K, Mischel Paul S, Phelps Michael, Parada Luis F, Liu Xin, Sofroniew Michael V, Eilber Fritz C, Wu Hong PTEN dosage is essential for neurofibroma development and malignant transformation Proceedings of the National Academy of Sciences of the United States of America, 2009; 106(46): 19479-84.

Courtine Grégoire, Gerasimenko Yury, van den Brand Rubia, Yew Aileen, Musienko Pavel, Zhong Hui, Song Bingbing, Ao Yan, Ichiyama Ronaldo M, Lavrov Igor, Roy Roland R, Sofroniew Michael V, Edgerton V Reggie Transformation of nonfunctional spinal circuits into functional states after the loss of brain input Nature neuroscience, 2009; 12(10): 1333-42.

Voskuhl Rhonda R, Peterson R Scott, Song Bingbing, Ao Yan, Morales Laurie Beth J, Tiwari-Woodruff Seema, Sofroniew Michael V Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(37): 11511-22.

Yang Chu-Ya, Song Bingbing, Ao Yan, Nowak Andrew P, Abelowitz Ryan B, Korsak Rose A, Havton Leif A, Deming Timothy J, Sofroniew Michael V Biocompatibility of amphiphilic diblock copolypeptide hydrogels in the central nervous system Biomaterials, 2009; 30(15): 2881-98.

Gregorian Caroline, Nakashima Jonathan, Le Belle Janel, Ohab John, Kim Rachel, Liu Annie, Smith Kate Barzan, Groszer Matthias, Garcia A Denise, Sofroniew Michael V, Carmichael S Thomas, Kornblum Harley I, Liu Xin, Wu Hong Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(6): 1874-86.

Herrmann Julia E, Imura Tetsuya, Song Bingbing, Qi Jingwei, Ao Yan, Nguyen Thu K, Korsak Rose A, Takeda Kiyoshi, Akira Shizuo, Sofroniew Michael V STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008; 28(28): 7231-43.

Lepore Angelo C, Dejea Christine, Carmen Jessica, Rauck Britta, Kerr Douglas A, Sofroniew Michael V, Maragakis Nicholas J Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration Experimental neurology, 2008; 211(2): 423-32.

Shigetomi Eiji, Bowser David N, Sofroniew Michael V, Khakh Baljit S Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008; 28(26): 6659-63.

Otis Thomas S, Sofroniew Michael V Glia get excited Nature neuroscience, 2008; 11(4): 379-80.

Courtine Gregoire, Song Bingbing, Roy Roland R, Zhong Hui, Herrmann Julia E, Ao Yan, Qi Jingwei, Edgerton V Reggie, Sofroniew Michael V Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury Nature medicine, 2008; 14(1): 69-74.

Savidge Tor C, Sofroniew Michael V, Neunlist Michel Starring roles for astroglia in barrier pathologies of gut and brain Laboratory investigation; a journal of technical methods and pathology, 2007; 87(8): 731-6.

Savidge Tor C, Newman Paul, Pothoulakis Charalabos, Ruhl Anne, Neunlist Michel, Bourreille Arnaud, Hurst Roger, Sofroniew Michael V Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione Gastroenterology, 2007; 132(4): 1344-58.

Saxe Michael D, Malleret Gaël, Vronskaya Svetlana, Mendez Indira, Garcia A Denise, Sofroniew Michael V, Kandel Eric R, Hen René Paradoxical influence of hippocampal neurogenesis on working memory Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(11): 4642-6.

Saxe Michael D, Battaglia Fortunato, Wang Jing-Wen, Malleret Gael, David Denis J, Monckton James E, Garcia A Denise R, Sofroniew Michael V, Kandel Eric R, Santarelli Luca, Hen René, Drew Michael R Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus Proceedings of the National Academy of Sciences of the United States of America, 2006; 103(46): 17501-6.

Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV. Essential protective roles of reactive astrocytes in traumatic brain injury, Brain, 2006; 129(Pt 10): 2761-72.

Imura Tetsuya, Nakano Ichiro, Kornblum Harley I, Sofroniew Michael V Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes Glia, 2006; 53(3): 277-93.

Sofroniew Michael V Reactive astrocytes in neural repair and protection The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 2005; 11(5): 400-7.

Nakano Ichiro, Paucar Andres A, Bajpai Ruchi, Dougherty Joseph D, Zewail Amani, Kelly Theresa K, Kim Kevin J, Ou Jing, Groszer Matthias, Imura Tetsuya, Freije William A, Nelson Stanley F, Sofroniew Michael V, Wu Hong, Liu Xin, Terskikh Alexey V, Geschwind Daniel H, Kornblum Harley I Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation The Journal of cell biology, 2005; 170(3): 413-27.

Garcia A Denise R, Doan Ngan B, Imura Tetsuya, Bush Toby G, Sofroniew Michael V GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain Nature neuroscience, 2004; 7(11): 1233-41.

Faulkner Jill R, Herrmann Julia E, Woo Michael J, Tansey Keith E, Doan Ngan B, Sofroniew Michael V Reactive astrocytes protect tissue and preserve function after spinal cord injury The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004; 24(9): 2143-55.

Morshead Cindi M, Garcia A Denize, Sofroniew Michael V, van Der Kooy Derek The ablation of glial fibrillary acidic protein-positive cells from the adult central nervous system results in the loss of forebrain neural stem cells but not retinal stem cells The European journal of neuroscience, 2003; 18(1): 76-84.

Imura Tetsuya, Kornblum Harley I, Sofroniew Michael V The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003; 23(7): 2824-32.

Sofroniew, MV Howe, CL Mobley, WC Nerve growth factor signaling, neuroprotection, and neural repair Annual review of neuroscience. , 2001; 24: 1217-81.

Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice, Neuron, 1999; 23(2): 297-308.

Lam, HH Bhardwaj, A O’Connell, MT Hanley, DF Traystman, RJ Sofroniew, MV Nerve growth factor rapidly suppresses basal, NMDA-evoked, and AMPA-evoked nitric oxide synthase activity in rat hippocampus in vivo Proceedings of the National Academy of Sciences of the United States of America. , 1998; 95(18): 10926-31.

Kimonedes, V.G., Svendsen, C.N., Sofroniew, M.V. and Herbert, J. Dehydroepiandrosterone (DHEA) protects hippocampal neurons against NMDA-induced neurotoxicity, , 1998; Proc. Natl. Acad. Sci. USA 95: 1852-1857 .

Bush, TG Savidge, TC Freeman, TC Cox, HJ Campbell, EA Mucke, L Johnson, MH Sofroniew, MV Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice Cell. , 1998; 93(2): 189-201.