After spinal cord injury (SCI), a break in neural-immune homeostasis slows healing and causes damage, both in the injured spinal cord and in tissues found throughout the body. These complications impair neurological recovery and also increase morbidity and mortality. Discovery themes in the Popovich lab seek to overcome these adverse effects of aberrant neuro-immune crosstalk caused by SCI. Select publications from these research themes are below. 

 

Theme 1: What causes myeloid cells to both help and harm the injured spinal cord?

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• Brennan, F.H., Li, Y., Wang, C., Ma, A., Guo, Q., Li, Y., Pukos, N., Campbell, W.A., Witcher, K.G., Guan, Z., Kigerl, K.A., Hall, J.C.E, Godbout, J.P., Fischer, A.J., McTigue, D.M., He, Z., Ma, Q. and Popovich, P.G. Microglia coordinate cellular interactions during spinal cord repair in mice. Nature Communications. 2022 13, 4096

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• Madalena, K.M., Brennan, F.H., Popovich, P.G. 2022. Genetic deletion of the glucocorticoid receptor in Cx3cr1+ myeloid cells is neuroprotective and improves motor recovery after spinal cord injury. Experimental Neurology. 2022 355, 114114

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• Freria CM, Brennan FH, Sweet DR, Guan Z, Hall JC, Kigerl KA, Nemeth DP, Liu X, Lacroix S, Quan N, Popovich PG. Serial Systemic Injections of Endotoxin (LPS) Elicit Neuroprotective Spinal Cord Microglia through IL-1-Dependent Cross Talk with Endothelial Cells. J Neurosci. 2020 Nov 18;40(47):9103-9120. 

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• Gensel JC, Wang Y, Guan Z, Beckwith KA, Braun KJ, Wei P, McTigue DM, Popovich PG. Toll-Like Receptors and Dectin-1, a C-Type Lectin Receptor, Trigger Divergent Functions in CNS Macrophages. J Neurosci. 2015 Jul 8;35(27):9966-76. 

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• Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009 Oct 28;29(43):13435-44.

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Theme 2: Why does SCI cause pathology in organs found throughout the body?

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Sub-theme 1: Understanding spinal autonomic circuit plasticity after SCI​

• Brennan, F.H., Swarts, E.A., Kigerl, K.A., Mifflin K.A., Guan, Z, Noble, B.T., Wang, Y, Witcher, K.G., Godbout, J.P., Popovich, P.G. Microglia promote maladaptive plasticity in autonomic circuitry after spinal cord injury in mice. Sci Transl Med. 2024 Jun 12;16(751):eadi3259. doi: 10.1126/scitranslmed.adi3259. Epub 2024 Jun 12. PMID: 38865485

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• Noble, B.T., Brennan, F.H., Wang, Y., Guan, Z., Mo, X, Schwab, J.M., and Popovich, P.G. Thoracic VGlut2+ spinal interneurons regulate structural and functional plasticity of sympathetic networks after high-level spinal cord injury. J Neurosci. 2022 42(17):3659-3675   

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• ​Brennan FH, Noble BT, Wang Y, Guan Z, Davis H, Mo X, Harris C, Eroglu C, Ferguson AR, Popovich PG. Acute post-injury blockade of α2δ-1 calcium channel subunits prevents pathological autonomic plasticity after spinal cord injury. Cell Reports. 2021 Jan 26;34(4):108667.

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• Ueno M, Ueno-Nakamura Y, Niehaus J, Popovich PG, Yoshida Y. Silencing spinal interneurons inhibits immune suppressive autonomic reflexes caused by spinal cord injury. Nature Neuroscience. 2016 Jun;19(6):784-7.

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Sub-theme 2: SCI-induced suppression of systemic and tissue-specific immunity

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• Rodgers, K.A., Kigerl K.A., Schwab J.M., Popovich P.G. Immune dysfunction after spinal cord injury - A review of autonomic and neuroendocrine mechanisms. Curr Opin Pharmacol. 2022 Jun;64:102230. 

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• Mifflin, K.A., Brennan F.H., Guan, Z., Kigerl, K.A., Filous, A., Schwab J.M., Popovich, P.G. Spinal cord injury impairs lung immunity in mice. Journal of Immunology, 2022 209(1):157-170.

 

• Carpenter RS, Marbourg JM, Brennan FH, Mifflin KA, Hall JCE, Jiang RR, Mo XM, Karunasiri M, Burke MH, Dorrance AM, Popovich PG. Spinal cord injury causes chronic bone marrow failure. Nature Communications. 2020 Jul 24;11(1):3702.

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• Noble BT, Brennan FH, Popovich PG. The spleen as a neuroimmune interface after spinal cord injury. J Neuroimmunol. 2018 Aug 15;321:1-11.

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• Marbourg JM, Bratasz A, Mo X, Popovich PG. Spinal Cord Injury Suppresses Cutaneous Inflammation: Implications for Peripheral Wound Healing. J Neurotrauma. 2017 Mar 15;34(6):1149-1155. 

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• Zhang Y, Guan Z, Reader B, Shawler T, Mandrekar-Colucci S, Huang K, Weil Z, Bratasz A, Wells J, Powell ND, Sheridan JF, Whitacre CC, Rabchevsky AG, Nash MS, Popovich PG. Autonomic dysreflexia causes chronic immune suppression after spinal cord injury. J Neurosci. 2013 Aug 7;33(32):12970-81.

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• Lucin, KM, Sanders, VM, Jones, TB, Malarkey, WB, Popovich PG. Impaired antibody synthesis after spinal cord injury is level dependent and is due to sympathetic nervous system dysregulation. Exp Neurol. 2007 Sep 207(1):75-84.

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Sub-theme 3: SCI effects on the gut microbiota

• Du J, Zayed AA, Kigerl KA, Zane K, Sullivan MB, Popovich PG.Spinal Cord Injury Changes the Structure and Functional Potential of Gut Bacterial and Viral Communities. mSystems. 2021 May 11;6(3):e01356-20.

 

• Kigerl KA, Zane K, Adams K, Sullivan MB, Popovich PG. ​The spinal cord-gut- immune axis as a master regulator of health and neurological function after spinal cord injury. Exp Neurol. 2020 Jan;323:113085. 

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• Kigerl KA, Mostacada K, Popovich PG. Gut Microbiota Are Disease-Modifying Factors After Traumatic Spinal Cord Injury. Neurotherapeutics. 2018 Jan;15(1):60-67

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• Kigerl KA, Hall JC, Wang L, Mo X, Yu Z, Popovich PG. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016 Nov 14;213(12):2603-2620

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Check out the full list of Popovich Lab research publications here!

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Current Poppers

Lori Hudson, Lab manager

Krissy Kigerl, Research Scientist

Jodie Hall, Research Scientist

Zhen Guan, Technician

Ajay Medipally, Technician​

Katherine Mifflin, Post-doc

Elham AsghariAdib, Post-doc

Kyleigh Rodgers, MD.PhD student

Madeline Howarth, MD.PhD student

Ashley Cyr, BSc. student

Weston Misel, BSc. student

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Popovich Lab PhD and Post-doc Alum

• Faith Brennan, Research Scientist, PhD - currently Assistant Professor at Queen's University, Canada

• Kathryn Madalena, PhD - currently Assistant Scientific Director at ProEd Regulatory

• Pilar Manrique, PhD - currently Research Scientist at MicroViable Therapeutics, Spain

• Yonaida Valentine, PhD student

• Manoj Gottipati, PhD - currently Senior Scientist at Convelo Therapeutics, Cleveland

• Ben Noble, PhD - currently Medical Science Liaison, AbbVie

• Jessica Marbourg, PhD - currently Senior Scientist, AbbVie

• Randall Carpenter, PhD - currently post-doc at Einstein College of Medicine, New York

• Yan Wang, PhD - currently Senior Research Associate, Dept of Neurology, Ohio State University

• Camila Marques de Freria, PhD - currently Assistant Project Scientist, University of California San Diego

• Andrew Gaudet, PhD - currently Assistant Professor, University of Texas at Austin

• Shweta Mandrekar, PhD - currently Medical Science Liaison, Phathom Pharmaceuticals, OH.

• Denise Puga, PhD - currently Human Research Protection Program Coordinator, Texas A&M University

• Yi Zhang, PhD - currently staff scientist, FDA

• John Gensel, PhD - currently Associate Professor, University of Kentucky

• Alicia Hawthorne, PhD - currently Assistant Professor, University of Central Florida

• Jessica Alexander, PhD - currently Global Medical Director, Neurology at Jazz Pharmaceuticals

• Satoshi Nakamura, MD - currently Dept. of Neurosurgery Chair, Isehara Kyodo Hospital, Japan

• Daniel Ankeny, PhD - Anesthesiologist, Massachusetts General Hospital, MA

• Kurt Lucin, PhD - currently Assistant Professor, Eastern Connecticut State University

• Erin McDaniel, MD, PhD - Assistant Professor of Neurology, Yale School of Medicine, CT

• T Bucky Jones, PhD - currently Associate Prof, Midwestern University, AZ

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