Bowen Zhou earned his Bachelor of Science in Engineering from Princeton University in 2012, where he studied biofilm resistance in the laboratory of Dr. Mark Brynildsen. He then joined the laboratory of Dr. Gilbert Di Paolo at Columbia University, focusing on lipid biology in neurodegenerative disease. Dr. Zhou subsequently matriculated into the Medical Scientist Training Program at ÐÓ°ÉÊÓƵ, completing his Ph.D. under Dr. Derek Abbott. His doctoral research explored novel inflammatory mechanisms of cell death, particularly in malignant hematologic contexts.
Following medical school, he conducted postdoctoral research with Dr. Alvin Schmaier, investigating the role of tyrosine kinase inhibitors in thrombosis and programmed cell death. He is currently a resident physician in the Clinical Pathology Research Track at University Hospitals Cleveland Medical Center and a Clinical Instructor at ÐÓ°ÉÊÓƵ.
Research Information
Research Projects
The Zhou lab aims to study modern pathways of cell death and inflammation through molecular, genetic, and pharmacologic strategies. Cell death is a universal phenomenon that has been historically categorized as apoptosis and necrosis. Current knowledge recognizes over a dozen molecularly defined pathways of cell death, but clinical and translational application of these pathways has trailed far behind. We are specifically interested in forms of cell death that effect lysis of the cell with concurrent inflammation. This process, termed pyroptosis, relies on activation of self-inhibited pore-forming proteins that oligomerize in membranes after cleavage by caspases and other proteases, in effect collapsing membrane gradients. Our prior work established the central importance of discerning the exact order and type of cell death activation in leukemic cells; a major future direction of the lab is to further investigate these findings in clinical samples.
External Appointments
Publications
https://orcid.org/0000-0003-4421-9787
Zhou B, Abbott DW. Chemical modulation of gasdermin D activity: Therapeutic implications and consequences. Semin Immunol. 2023 Nov;70:101845. doi:10.1016/j.smim.2023.101845. Epub 2023 Oct 8. PMID: 37806032; PMCID: PMC10841450.
Zhou B*, Ryder CB*, Dubyak GR, Abbott DW. Gasdermins and pannexin-1 mediate pathways of chemotherapy-induced cell lysis in hematopoietic malignancies. Sci Signal. 2022 Dec 20;15(765):eabl6781. doi:10.1126/scisignal.abl6781. PMID: 36538593; PMCID: PMC9841445.
Miranda AM, Ashok A, Chan RB, Zhou B, Xu Y, McIntire LB, et al. Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice. Transl Psychiatry. 2022 Mar 29;12(1):129. doi:10.1038/s41398-022-01881-6. PMID: 35351864; PMCID: PMC8964762.
Ryder CB, Kondolf HC, O'Keefe ME, Zhou B, Abbott DW. Chemical modulation of gasdermin-mediated pyroptosis and therapeutic potential. J Mol Biol. 2022 Feb 28;434(4):167183. doi:10.1016/j.jmb.2021.167183. Epub 2021 Aug 3. PMID: 34358546; PMCID: PMC8810912.
Zhou B, Abbott DW. Gasdermin E permits interleukin-1 beta release in distinct sublytic and pyroptotic phases. Cell Rep. 2021 Apr 13;35(2):108998. doi:10.1016/j.celrep.2021.108998. PMID: 33852854; PMCID: PMC8106763.
Liu Z, Wang C, Yang J, Chen Y, Zhou B, Abbott DW, Xiao TS. Caspase-1 engages full-length gasdermin D through two distinct interfaces that mediate caspase recruitment and substrate cleavage. Immunity. 2020 Jul 14;53(1):106–114.e5. doi:10.1016/j.immuni.2020.06.007. PMID: 32553275; PMCID: PMC7382298.
Iaea DB, Spahr ZR, Singh RK, Chan RB, Zhou B, Bareja R, et al. Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Apr;1865(4):158609. doi:10.1016/j.bbalip.2020.158609. PMID: 31917335; PMCID: PMC6996790.
Liu Z, Wang C, Yang J, Zhou B, Yang R, Ramachandran R, et al. Crystal structures of the full-length murine and human gasdermin D reveal mechanisms of autoinhibition, lipid binding, and oligomerization. Immunity. 2019 Jul 16;51(1):43–49.e4. doi:10.1016/j.immuni.2019.04.017. PMID: 31097341; PMCID: PMC6640092.
Niemi JP, Filous AR, DeFrancesco A, Lindborg JA, Malhotra NA, Wilson GN, Zhou B, et al. Injury-induced gp130 cytokine signaling in peripheral ganglia is reduced in diabetes mellitus. Exp Neurol. 2017 Oct;296:1–15. doi:10.1016/j.expneurol.2017.06.020. PMID: 28645526; PMCID: PMC6442943.
Chan RB, Perotte AJ, Zhou B, Liong C, Shorr EJ, Marder KS, et al. Elevated GM3 plasma concentration in idiopathic Parkinson’s disease: A lipidomic analysis. PLoS One. 2017;12(2):e0172348. doi:10.1371/journal.pone.0172348. PMID: 28212433; PMCID: PMC5315374.
Holland P, Knævelsrud H, Søreng K, Mathai BJ, Lystad AH, Pankiv S, et al. HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat Commun. 2016 Dec 22;7:13889. doi:10.1038/ncomms13889. PMID: 28004827; PMCID: PMC5412012.
Marquer C, Tian H, Yi J, Bastien J, Dall’Armi C, Yang-Klingler Y, Zhou B, et al. Arf6 controls retromer traffic and intracellular cholesterol distribution via a phosphoinositide-based mechanism. Nat Commun. 2016 Jun 23;7:11919. doi:10.1038/ncomms11919. PMID: 27336679; PMCID: PMC4931008.
Oliveira TG, Chan RB, Bravo FV, Miranda A, Silva RR, Zhou B, et al. The impact of chronic stress on the rat brain lipidome. Mol Psychiatry. 2016 Jan;21(1):80–88. doi:10.1038/mp.2015.14. PMID: 25754084; PMCID: PMC4565780.
Vevea JD, Garcia EJ, Chan RB, Zhou B, Schultz M, Di Paolo G, et al. Role for lipid droplet biogenesis and microlipophagy in adaptation to lipid imbalance in yeast. Dev Cell. 2015 Dec 7;35(5):584–599. doi:10.1016/j.devcel.2015.11.010. PMID: 26651293; PMCID: PMC4679156.
Gulati S, Ekland EH, Ruggles KV, Chan RB, Jayabalasingham B, Zhou B, et al. Profiling the essential nature of lipid metabolism in asexual blood and gametocyte stages of Plasmodium falciparum. Cell Host Microbe. 2015 Sep 9;18(3):371–381. doi:10.1016/j.chom.2015.08.003. PMID: 26355219; PMCID: PMC4567697.
Kett LR, Stiller B, Bernath MM, Tasset I, Blesa J, Jackson-Lewis V, Chan RB, Zhou B, et al. α-Synuclein-independent histopathological and motor deficits in mice lacking the endolysosomal Parkinsonism protein Atp13a2. J Neurosci. 2015 Apr 8;35(14):5724–5742. doi:10.1523/JNEUROSCI.0632-14.2015. PMID: 25855184; PMCID: PMC4388928