Bogdan K. Beirowski MD, PhD
Bogdan K. Beirowski
MD, PhD
Assistant Professor of Biochemistry, Principal Investigator at the Institute for Myelin and Glia Exploration
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Apoptosis and cell death; Bioinformatics; Metabolism; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Neurobiology
Professional Summary:
My laboratory studies the cell-autonomous and non-cell-autonomous mechanisms of axon degeneration, a process akin to programmed cell death. In other words, we are attempting to elucidate what causes axon breakdown from within neurons and which external (glial) events trigger axon loss. Degeneration of axons is a hallmark in many neurodegenerative conditions, including those associated with abnormal glia. We have great hope that understanding why and how axons degenerate may lead to more efficient neuroprotective therapies tailored specifically to support axons and their surrounding glia.
Axons are the longest cellular projections of neurons relaying electrical and biochemical signals in nerves and white-matter tracts of the nervous system. As such, they are critical for neuronal wiring and transport of neuronal maintenance signals. Because of their incredible length and energetic demand (human motor neurons can be one meter long), however, axons are very vulnerable and at continuous risk of damage. Axons do not exist in isolation but are inextricably and intimately associated with their enwrapping glia (Schwann cells and oligodendrocytes) to form a unique axon-glia unit.
The most relevant neurological symptoms in a number of debilitating neurodegenerative conditions are due to compromised axon integrity. Thus, neuroprotective therapies promoting axon stability have great potential for more effective treatment. Recent studies indicate that axonal degeneration, at least in experimental settings, is an active and highly regulated process akin to programmed cell death (‘axonal auto-destruction’). Moreover, it is increasingly realized that axonal maintenance relies not only on neuron-derived provisions but also on trophic support from their enwrapping glia. The mechanism for this non-cell-autonomous support function remains unknown, but emerging evidence indicates that it is distinct from the glial role in insulating axons with myelin.
We are pursuing the intriguing question of whether abolished support by aberrant delivery of metabolites and other trophic factors from glia into axons is mechanistically linked to the induction of axonal auto-destruction. This concept is supported by our recent finding that metabolic dysregulation exclusively in Schwann cells is sufficient to trigger axon breakdown.
Education and Training:
- PhD, Molecular Biology, University of Cambridge (2010)
- Medicine, University of Cologne (2005)
Employment:
- Assistant Professor, Department of Biochemistry, Hunter James Kelly Research Institute (2016-present)
- Post Doctoral Fellow, Department of Genetics, Washington University School of Medicine (2010–2016)
Grants and Sponsored Research:
- August 2021–June 2026
Energizing and protecting axons through metabolic coupling to Schwann cells.
NIH, NINDS
Role: Co-Investigator
$376,139 - February 2020–December 2024
Elucidating the trophic support of long axons by metabolic signaling in oligodendrocytes
NINDS
Role: Principal Investigator
$1,929,160 - June 2021–June 2022
An innovative instrument cluster for the integrative behavioral analysis of mouse mutants with perturbed neuronal connectivity
NIH, ORIP
Role: Principal Investigator
$173,221 - August 2018–January 2022
Deciphering metabolic support of axons by LKB1 signaling in Schwann cells
Muscular Dystrophy Association
Role: Principal Investigator
$300,000 - August 2012–July 2015
Modeling Axon Loss in CMT by Disruption of Schwann Cell Metabolic Regulation
Muscular Dystrophy Association
Role: Principal Investigator
$180,000
Journal Articles:
- Beirowski B, Wong KM, Babetto E, Milbrandt J, Beirowski BK. (2017) mTORC1 promotes proliferation of immature Schwann cells and myelin growth of differentiated Schwann cells. Proc Natl Acad Sci U S A (Jan), 114(21): 4261-4270.
- Beirowski B, Babetto E, Golden JP, Chen YJ, Yang K, Gross RW, Patti GJ, Milbrandt J. (2014) Metabolic regulator LKB1 is crucial for Schwann cell-mediated axon maintenance. Nat Neurosci (Oct), 17(10): 1351-1361.
- Beirowski B. (2013) Concepts for regulation of axon integrity by enwrapping glia. Front Cell Neurosci (Dec), 7: 256-256.
- Babetto E, Beirowski B, Russler EV, Milbrandt J, DiAntonio A, Beirowski BK. (2013) The Phr1 ubiquitin ligase promotes injury-induced axon self-destruction. Cell Rep (May), 3(5): 1422-1429.
- Babetto E, Beirowski B, Janeckova L, Brown R, Gilley J, Thomson D, Ribchester RR, Coleman MP, Beirowski BK. (2010) Targeting NMNAT1 to axons and synapses transforms its neuroprotective potency in vivo. J Neurosci (Oct), 30(40): 13291-13304.
- Beirowski B, Babetto E, Coleman MP, Martin KR, Beirowski BK. (2008) The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model. Eur J Neurosci (Sep), 28(6): 1166-1179.
- Della-Flora Nunes G, Wilson ER, Marziali LN, Hurley E, Silvestri N, He B, O. (2021) Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells. Nature communications (Jun), 12(1): 3285. doi:10.1038/s41467-021-23552-8
- Babetto E, Wong KM, Beirowski B. (2020) A glycolytic shift in Schwann cells supports injured axons. Nature neuroscience (Oct), 23(10): 1215-1228.
- Beirowski B. (2020) Measuring Bioenergetic Signatures of Peripheral Nerve Segments by Extracellular Flux Analysis. Methods in molecular biology (Clifton, N.J.) (Jan), 2143: 191-203.
- Beirowski B, Beirowski BK. (2019) The LKB1-AMPK and mTORC1 Metabolic Signaling Networks in Schwann Cells Control Axon Integrity and Myelination: Assembling and upholding nerves by metabolic signaling in Schwann cells. Bioessays (Jan), 41(1): 1800075-1800075.
- Wong KM, Beirowski B, Beirowski BK. (2018) Multiple lines of inhibitory feedback on AKT kinase in Schwann cells lacking TSC1/2 hint at distinct functions of mTORC1 and AKT in nerve development. Commun Integr Biol (Feb), 11(1): 1433441-1433441.
- Beirowski B, Wong KM, Beirowski BK. (2017) mTORC1 promotes Schwann cell cycling and myelinogenesis. Cell Cycle (Sep), 16(18): 1637-1638.
- Wong KM, Babetto E, Beirowski B, Beirowski BK. (2017) Axon degeneration: make the Schwann cell great again. Neural Regen Res (Apr), 12(4): 518-524.
- Beirowski B, Babetto E, Wrabetz L, Beirowski BK. (2016) Axon degeneration: Linking axonal bioenergetics to myelin. J Cell Biol (Nov), 215(4): 437-440.
- Shin JE, Cho Y, Beirowski B, Milbrandt J, Cavalli V, DiAntonio A, Beirowski BK. (2012) Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron (Jun), 74(6): 1015-1022.
- Beirowski J, Inghelbrecht S, Arien A, Gieseler H. (2012) Freeze-drying of nanosuspensions, part 3: investigation of factors compromising storage stability of highly concentrated drug nanosuspensions. Journal of pharmaceutical sciences (Jan), 101(1): 354-62.
- Beirowski J, Inghelbrecht S, Arien A, Gieseler H. (2011) Freeze drying of nanosuspensions, 2: the role of the critical formulation temperature on stability of drug nanosuspensions and its practical implication on process design. Journal of pharmaceutical sciences (Oct), 100(10): 4471-81.
- Beirowski B, Gustin J, Armour SM, Yamamoto H, Viader A, North BJ, Michán S, Baloh RH, Golden JP, Schmidt RE, Sinclair DA, Auwerx J, Milbrandt J, Beirowski BK. (2011) Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc Natl Acad Sci U S A (Oct), 108(43): 952-961.
- Beirowski J, Inghelbrecht S, Arien A, Gieseler H. (2011) Freeze-drying of nanosuspensions, 1: freezing rate versus formulation design as critical factors to preserve the original particle size distribution. Journal of pharmaceutical sciences (May), 100(5): 1958-68.
- Gross O, Girgert R, Beirowski B, Kretzler M, Kang HG, Kruegel J, Miosge N, Busse AC, Segerer S, Vogel WF, Müller GA, Weber M. (2010) Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease. Matrix biology : journal of the International Society for Matrix Biology (Jun), 29(5): 346-56.
- Beirowski B, Nógrádi A, Babetto E, Garcia-Alias G, Coleman MP, Beirowski BK. (2010) Mechanisms of axonal spheroid formation in central nervous system Wallerian degeneration. J Neuropathol Exp Neurol (May), 69(5): 455-472.
- Beirowski B, Morreale G, Conforti L, Mazzola F, Di Stefano M, Wilbrey A, Babetto E, Janeckova L, Magni G, Coleman MP, Beirowski BK. (2010) WldS can delay Wallerian degeneration in mice when interaction with valosin-containing protein is weakened. Neuroscience (Mar), 166(1): 201-211.
- Conforti L, Wilbrey A, Morreale G, Janeckova L, Beirowski B, Adalbert R, Mazzola F, Di Stefano M, Hartley R, Babetto E, Smith T, Gilley J, Billington RA, Genazzani AA, Ribchester RR, Magni G, Coleman M, Beirowski BK. (2009) Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice. J Cell Biol (Feb), 184(4): 491-500.
- Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, Janeckova L, Magni G, Ribchester RR, Coleman MP, Beirowski BK. (2009) Non-nuclear Wld(S) determines its neuroprotective efficacy for axons and synapses in vivo. J Neurosci (Jan), 29(3): 653-668.
- Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, Janeckova L, Magni G, Ribchester RR, Coleman MP. (2009) Non-nuclear WldS determines its neuroprotective efficacy for axons and synapses. J Neurosci (Jan), 29(3): 653-668.
- Wilbrey AL, Haley JE, Wishart TM, Conforti L, Morreale G, Beirowski B, Babetto E, Adalbert R, Gillingwater TH, Smith T, Wyllie DJ, Ribchester RR, Coleman MP, Beirowski BK. (2008) VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, Wld(S). Mol Cell Neurosci (Jul), 38(3): 325-340.
- Koepke ML, Weber M, Schulze-Lohoff E, Beirowski B, Segerer S, Gross O. (2007) Nephroprotective effect of the HMG-CoA-reductase inhibitor cerivastatin in a mouse model of progressive renal fibrosis in Alport syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Apr), 22(4): 1062-9.
- Conforti L, Fang G, Beirowski B, Wang MS, Sorci L, Asress S, Adalbert R, Silva A, Bridge K, Huang XP, Magni G, Glass JD, Coleman MP, Beirowski BK. (2007) NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration. Cell Death Differ (Jan), 14(1): 116-127.
- Beirowski B, Weber M, Gross O. (2006) Chronic renal failure and shortened lifespan in COL4A3+/- mice: an animal model for thin basement membrane nephropathy. Journal of the American Society of Nephrology : JASN (Jul), 17(7): 1986-94.
- Laser H, Conforti L, Morreale G, Mack TG, Heyer M, Haley JE, Wishart TM, Beirowski B, Walker SA, Haase G, Celik A, Adalbert R, Wagner D, Grumme D, Ribchester RR, Plomann M, Coleman MP, Beirowski BK. (2006) The slow Wallerian degeneration protein, WldS, binds directly to VCP/p97 and partially redistributes it within the nucleus. Mol Biol Cell (Mar), 17(3): 1075-1084.
- Gross O, Koepke ML, Beirowski B, Schulze-Lohoff E, Segerer S, Weber M. (2005) Nephroprotection by antifibrotic and anti-inflammatory effects of the vasopeptidase inhibitor AVE7688. Kidney international (Aug), 68(2): 456-63.
- Coleman MP, Adalbert R, Beirowski B. (2005) Neuroprotective strategies in MS: lessons from C57BL/Wld(S) mice. J Neurol Sci (Jun), 233(1-2): 133-138.
- Beirowski B, Adalbert R, Wagner D, Grumme DS, Addicks K, Ribchester RR, Coleman MP, Beirowski BK. (2005) The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves. BMC Neurosci (Feb), 6: 6-6.
- Mi W, Beirowski B, Gillingwater TH, Adalbert R, Wagner D, Grumme D, Osaka H, Conforti L, Arnhold S, Addicks K, Wada K, Ribchester RR, Coleman MP, Beirowski BK. (2005) The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice. Brain (Feb), 128(Pt 2): 405-416.
- Adalbert R, Gillingwater TH, Haley JE, Bridge K, Beirowski B, Berek L, Wagner D, Grumme D, Thomson D, Celik A, Addicks K, Ribchester RR, Coleman MP. (2005) A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses. The European journal of neuroscience (Jan), 21(1): 271-7.
- Gross O, Beirowski B, Harvey SJ, McFadden C, Chen D, Tam S, Thorner PS, Smyth N, Addicks K, Bloch W, Ninomiya Y, Sado Y, Weber M, Vogel WF. (2004) DDR1-deficient mice show localized subepithelial GBM thickening with focal loss of slit diaphragms and proteinuria. Kidney international (Jul), 66(1): 102-11.
- Gross O, Schulze-Lohoff E, Koepke ML, Beirowski B, Addicks K, Bloch W, Smyth N, Weber M. (2004) Antifibrotic, nephroprotective potential of ACE inhibitor vs AT1 antagonist in a murine model of renal fibrosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Jul), 19(7): 1716-23.
- Beirowski B, Berek L, Adalbert R, Wagner D, Grumme DS, Addicks K, Ribchester RR, Coleman MP, Beirowski BK. (2004) Quantitative and qualitative analysis of Wallerian degeneration using restricted axonal labelling in YFP-H mice. J Neurosci Methods (Mar), 134(1): 23-35.
- Gross O, Beirowski B, Koepke ML, Kuck J, Reiner M, Addicks K, Smyth N, Schulze-Lohoff E, Weber M. (2003) Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney international (Feb), 63(2): 438-46.
- Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Fernando FS, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP, Beirowski BK. (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci (Dec), 4(12): 1199-1206.
Professional Memberships:
- Federation of European Neuroscience Societies (FENS); Membership (2009–present)
- German Neuroscience Society (NWG); Membership (2009–present)
Presentations:
- "Regulation of axon stability by metabolic coupling to Schwann cells" seminar, Charcot-Marie-Tooth Association (2021)
- "Regulation of axon integrity by axoglial metabolic coupling" El Club de la glía, Facultad de Medicina, Universidad de Buenos Aires – Argentinia (2021)
- "Regulation of axon stability by axoglial metabolic coupling" seminar, Weill Cornell Medicine, Burke Neurological Institute (2021)
- "Regulation of axon integrity by axoglial metabolic coupling" Peripheral Nerve Society (PNS) Annual Meeting (2021)
- "Regulation of axon stability by axoglial metabolic coupling" Biogen Discovery Seminar, Biogen (2021)
- "Regulation of axon stability by axoglial metabolic coupling" Seminar, Philips University of Marburg (2021)
Service Activities:
- Department of Defense (DoD) Regeneration and Remyelination-1 (RR-1) peer review panel FY21 Multiple Sclerosis Research Program (MSRP); Grant Reviewer (2021)
- NIH grant review study section ‚Biomedical Imaging and Metabolism Instrumentation S10 Grant Programs‘; Grant Reviewer (2021)
- Frontiers in Neuroscience; Associate Editor (2021–present)
- Nutrients; Editorial Board Member (2020–present)
- ; PhD Program in the Biomedical Sciences (PPBS) Admissions Committee member, secondary (2018–2019)
- ; Collegiate Science & Technology Entry Program (CSTEP) Summer Research Program for underrepresented students, poster judge for CSTEP Annual Symposium (2018)
- ; Review Committee member (chaired by Kenneth Tramposch), University IMPACT LIFE SCIENCES grant program (2017–2018)
- Neural Regeneration Research; Editorial Board Member (2017–present)
- ; Department of Biochemistry Faculty Council member (2015–present)
- Ad hoc reviewer for 'Nature', 'Nature Neuroscience', 'Nature Aging', 'Nature Communications', 'Journal of Experimetal Medicine', 'Cell Reports', 'eLife', ‚PLOS Biology‘, 'Science Signaling', 'Neurotherapeutics', 'Neurobiology of Disease', 'Glia', 'BMC Biology', 'Journal of Neuroscience' (approx. 20 reviewed manuscripts since 2007), 'Molecular Neurobiology', 'Frontiers in Neuroscience', 'Journal of Neurochemistry', 'Nutrients', 'Molecular and Cellular Neuroscience', 'Biomolecules', 'Experimental Neurology', 'Brain Communications', Neuropharmacology', 'Scientific Reports', 'Neural Regeneration Research', 'International Journal for Molecular Sciences', 'Neuroendocrinology', 'PLOS One', 'Journal of Biomolecular Structure and Dynamics', 'Journal of Anatomy', 'Molecular Biology Reports', 'ISRN Neuroscience', 'BBA Molecular Basis of Disease', 'FEBS Letters', 'Neuroscience Letters'. 'JoVE', 'Current Drug Research Reviews' (2007–present)