Skip to main content

Publications

Research Publications

Bryan III MR, Tian X, Tseng JH, Evangelista BA, Ragusa JV, Bryan AF, Trotman W, Irwin D, Cohen TJ. Development and characterization of novel anti-acetylated tau monoclonal antibodies to probe pathogenic tau species in Alzheimer’s disease. Acta Neuropathol Commun. 2024 Oct 12;12(1):163. doi: 10.1186/s40478-024-01865-1. PMID: 39396065; PMCID: PMC11470691.

Necarsulmer JC, Simon JM, Evangelista BA, Chen Y, Tian X, Nafees S, Marquez AB, Jiang H, Wang P, Ajit D, Nikolova VD, Harper KM, Ezzell JA, Lin FC, Beltran AS, Moy SS, Cohen TJ. RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy. Elife. 2023 Oct 11;12. doi: 10.7554/eLife.85921. PubMed PMID: 37819053; PubMed Central PMCID: PMC10567115.

Opland CK, Bryan MR, Harris B, McGillion-Moore J, Tian X, Chen Y, Itano MS, Diering GH, Meeker RB, Cohen TJ. Activity-dependent tau cleavage by caspase-3 promotes neuronal dysfunction and synaptotoxicity. iScience. 2023 Jun 16;26(6):106905. doi: 10.1016/j.isci.2023.106905. eCollection 2023 Jun 16. PubMed PMID: 37305696; PubMed Central PMCID: PMC10251131.

Evangelista BA, Cahalan SR, Ragusa JV, Mordant A, Necarsulmer JC, Perna RJ, Ajit T, White K, Barker NK, Tian X, Cohen S, Meeker R, Herring LE, Cohen TJ. Tandem detergent-extraction and immunoprecipitation of proteinopathy: Scalable enrichment of ALS-associated TDP-43 aggregates. iScience. 2023 May 19;26(5):106645. doi: 10.1016/j.isci.2023.106645. eCollection 2023 May 19. PubMed PMID: 37182104; PubMed Central PMCID: PMC10173608.

Wander CM, Li YD, Bao H, Asrican B, Luo YJ, Sullivan HA, Chao TH, Zhang WT, Chéry SL, Tart DS, Chen ZK, Shih YI, Wickersham IR, Cohen TJ, Song J. Compensatory remodeling of a septo-hippocampal GABAergic network in the triple transgenic Alzheimer’s mouse model. J Transl Med. 2023 Apr 15;21(1):258. doi: 10.1186/s12967-023-04078-7. PubMed PMID: 37061718; PubMed Central PMCID: PMC10105965.

Wander CM, Tsujimoto THM, Ervin JF, Wang C, Maranto SM, Bhat V, Dallmeier JD, Wang SJ, Lin FC, Scott WK, Holtzman DM, Cohen TJ. Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease. Acta Neuropathol Commun. 2022 Aug 8;10(1):110. doi: 10.1186/s40478-022-01409-5. PubMed PMID: 35941704; PubMed Central PMCID: PMC9361643.

Tabassum Z, Tseng JH, Isemann C, Tian X, Chen Y, Herring LE, Cohen TJ. Identification of a reciprocal negative feedback loop between tau-modifying proteins MARK2 kinase and CBP acetyltransferase. J Biol Chem. 2022 Jun;298(6):101977. doi: 10.1016/j.jbc.2022.101977. Epub 2022 Apr 22. PubMed PMID: 35469920; PubMed Central PMCID: PMC9136110.

Quiroga IY, Cruikshank AE, Bond ML, Reed KSM, Evangelista BA, Tseng JH, Ragusa JV, Meeker RB, Won H, Cohen S, Cohen TJ, Phanstiel DH. Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems. J Neuroinflammation. 2022 Apr 23;19(1):99. doi: 10.1186/s12974-022-02459-1. PubMed PMID: 35459147; PubMed Central PMCID: PMC9034485.

Tseng JH, Ajit A, Tabassum Z, Patel N, Tian X, Chen Y, Prevatte AW, Ling K, Rigo F, Meeker RB, Herring LE, Cohen TJ. Tau seeds are subject to aberrant modifications resulting in distinct signatures. Cell Rep. 2021 Apr 27;35(4):109037. doi: 10.1016/j.celrep.2021.109037. PubMed PMID: 33910013; PubMed Central PMCID: PMC8135111.

Trzeciakiewicz H, Ajit D, Tseng JH, Chen Y, Ajit A, Tabassum Z, Lobrovich R, Peterson C, Riddick NV, Itano MS, Tripathy A, Moy SS, Lee VMY, Trojanowski JQ, Irwin DJ, Cohen TJ. An HDAC6-dependent surveillance mechanism suppresses tau-mediated neurodegeneration and cognitive decline. Nat Commun. 2020 Nov 2;11(1):5522. doi: 10.1038/s41467-020-19317-4. PubMed PMID: 33139698; PubMed Central PMCID: PMC7606452.

Wander CM, Tseng JH, Song S, Al Housseiny HA, Tart DS, Ajit A, Ian Shih YY, Lobrovich R, Song J, Meeker RB, Irwin DJ, Cohen TJ. The Accumulation of Tau-Immunoreactive Hippocampal Granules and Corpora Amylacea Implicates Reactive Glia in Tau Pathogenesis during Aging. iScience. 2020 Jul 24;23(7):101255. doi: 10.1016/j.isci.2020.101255. Epub 2020 Jun 10. PubMed PMID: 32585593; PubMed Central PMCID: PMC7322077.

Ajit D, Trzeciakiewicz H, Tseng JH, Wander CM, Chen Y, Ajit A, King DP, Cohen TJ. A unique tau conformation generated by an acetylation-mimic substitution modulates P301S-dependent tau pathology and hyperphosphorylation. J Biol Chem. 2019 Nov 8;294(45):16698-16711. doi: 10.1074/jbc.RA119.009674. Epub 2019 Sep 22. PubMed PMID: 31543505; PubMed Central PMCID: PMC6851325.

Chen Y, Cohen TJ. Aggregation of the nucleic acid-binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation. J Biol Chem. 2019 Mar 8;294(10):3696-3706. doi: 10.1074/jbc.RA118.006351. Epub 2019 Jan 10. PubMed PMID: 30630951; PubMed Central PMCID: PMC6416430.

Tseng JH, Xie L, Song S, Xie Y, Allen L, Ajit D, Hong JS, Chen X, Meeker RB, Cohen TJ. The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology. Cell Rep. 2017 Aug 29;20(9):2169-2183. doi: 10.1016/j.celrep.2017.07.082. PubMed PMID: 28854366; PubMed Central PMCID: PMC5578720.

Wang P, Wander CM, Yuan CX, Bereman MS, Cohen TJ. Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program. Nat Commun. 2017 Jul 19;8(1):82. doi: 10.1038/s41467-017-00088-4. PubMed PMID: 28724966; PubMed Central PMCID: PMC5517419.

Trzeciakiewicz H, Tseng JH, Wander CM, Madden V, Tripathy A, Yuan CX, Cohen TJ. A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy. Sci Rep. 2017 Mar 13;7:44102. doi: 10.1038/srep44102. PubMed PMID: 28287136; PubMed Central PMCID: PMC5347034.

Hwang AW, Trzeciakiewicz H, Friedmann D, Yuan CX, Marmorstein R, Lee VM, Cohen TJ. Conserved Lysine Acetylation within the Microtubule-Binding Domain Regulates MAP2/Tau Family Members. PLoS One. 2016;11(12):e0168913. doi: 10.1371/journal.pone.0168913. eCollection 2016. PubMed PMID: 28002468; PubMed Central PMCID: PMC5176320.

Cohen TJ, Constance BH, Hwang AW, James M, Yuan CX. Intrinsic Tau Acetylation Is Coupled to Auto-Proteolytic Tau Fragmentation. PLoS One. 2016;11(7):e0158470. doi: 10.1371/journal.pone.0158470. eCollection 2016. PubMed PMID: 27383765; PubMed Central PMCID: PMC4934699.

Cohen TJ, Choi MC, Kapur M, Lira VA, Yan Z, Yao TP. HDAC4 regulates muscle fiber type-specific gene expression programs. Mol Cells. 2015 Apr;38(4):343-8. doi: 10.14348/molcells.2015.2278. Epub 2015 Feb 25. PubMed PMID: 25728750; PubMed Central PMCID: PMC4400309.

Cohen TJ, Hwang AW, Restrepo CR, Yuan CX, Trojanowski JQ, Lee VM. An acetylation switch controls TDP-43 function and aggregation propensity. Nat Commun. 2015 Jan 5;6:5845. doi: 10.1038/ncomms6845. PubMed PMID: 25556531; PubMed Central PMCID: PMC4407365.

Irwin DJ, Cohen TJ, Grossman M, Arnold SE, McCarty-Wood E, Van Deerlin VM, Lee VM, Trojanowski JQ.  Acetylated tau neuropathology in sporadic and hereditary tauopathies.  Am J Pathol. 2013 Aug;183(2):344-51. doi: 10.1016/j.ajpath.2013.04.025. PMID: 23885714

Todd J. Cohen, Dave Friedmann, Andrew W. Hwang, Ronen Marmorstein and Virginia M.Y. Lee: The microtubule-associated tau protein has intrinsic acetyltransferase activity.  Nature Structural & Molecular Biology. doi: 10.1038/nsmb.2555, Apr 2013.

Choi Moon-Chang*, Cohen Todd J*, Barrientos Tomasa, Wang Bin, Li Ming, Simmons Bryan J, Yang Jeong Soo, Cox Gregory A, Zhao Yingming, Yao Tso-Pang: A direct HDAC4-MAP kinase crosstalk activates muscle atrophy program. Molecular Cell 47(1): 122-32, Jul 2012. PMCID: PMC3398192

Irwin David J, Cohen Todd J, Grossman Murray, Arnold Steven E, Xie Sharon X, Lee Virginia M-Y, Trojanowski John Q: Acetylated tau, a novel pathological signature in Alzheimer’s disease and other tauopathies. Brain : a journal of neurology 135(Pt 3): 807-18, Mar 2012. PMCID: PMC3286338

Cohen Todd J, Hwang Andrew W, Unger Travis, Trojanowski John Q, Lee Virginia M Y: Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking. The EMBO journal31(5): 1241-52, Mar 2012. PMCID: PMC3297986

Cohen Todd J, Guo Jing L, Hurtado David E, Kwong Linda K, Mills Ian P, Trojanowski John Q, Lee Virginia M Y: The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nature Communications 2: 252, 2011. Research Article. PMCID: PMC3120096

Kozhemyakina Elena, Cohen Todd, Yao Tso-Pang, Lassar Andrew B: Parathyroid hormone-related peptide represses chondrocyte hypertrophy through a protein phosphatase 2A/histone deacetylase 4/MEF2 pathway. Molecular and Cellular Biology 29(21): 5751-62, Nov 2009. PMCID: PMC2772746

Cohen Todd J, Barrientos Tomasa, Hartman Zachary C, Garvey Sean M, Cox Gregory A, Yao Tso-Pang: The deacetylase HDAC4 controls myocyte enhancing factor-2-dependent structural gene expression in response to neural activity. FASEB journal 23(1): 99-106, Jan 2009. PMCID: PMC2626618

Cohen T J, Mallory M J, Strich R, Yao T-P: Hos2p/Set3p deacetylase complex signals secretory stress through the Mpk1p cell integrity pathway. Eukaryotic Cell 7(7): 1191-9, Jul 2008. PMCID: PMC2446675

Cohen Todd J, Waddell David S, Barrientos Tomasa, Lu Zhonghua, Feng Guoping, Cox Gregory A, Bodine Sue C, Yao Tso-Pang: The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming.The Journal of Biological Chemistry 282(46): 33752-9, Nov 2007.

Bolger Timothy A, Zhao Xuan, Cohen Todd J, Tsai Chih-Cheng, Yao Tso-Pang: The neurodegenerative disease protein ataxin-1 antagonizes the neuronal survival function of myocyte enhancer factor-2. The Journal of Biological Chemistry 282(40): 29186-92, Oct 2007.

Cohen Todd J, Lee Kun, Rutkowski Lisa H, Strich Randy: Ask10p mediates the oxidative stress-induced destruction of the Saccharomyces cerevisiae C-type cyclin Ume3p/Srb11p. Eukaryotic Cell 2(5): 962-70, Oct 2003. PMCID: PMC219367

Reviews:

Tseng JH, Cohen TJ. The emerging nontraditional roles for tau in the brain. Cytoskeleton (Hoboken). 2024 Jan;81(1):89-94. doi: 10.1002/cm.21811. Epub 2023 Dec 8. PubMed PMID: 38063261; PubMed Central PMCID: PMC11068308.

Cohen Todd J, Lee Virginia M Y, Trojanowski John Q: TDP-43 functions and pathogenic mechanisms implicated in TDP-43 proteinopathies. Trends in molecular medicine 17(11): 659-67, Nov 2011. PMCID: PMC3202652

Kovacs Jeffrey J, Cohen Todd J, Yao Tso-Pang: Chaperoning steroid hormone signaling via reversible acetylation. Nuclear receptor signaling 3: e004, 2005. PMCID: PMC1402214

Cohen Todd, Yao Tso-Pang: AcK-knowledge reversible acetylation. Science’s STKE : signal transduction knowledge environment 2004(245): pe42, Aug 2004.               

Book Chapters

Simmons Bryan J, Cohen Todd J, Bedlack Richard, Yao Tso-Pang: HDACs in skeletal muscle remodeling and neuromuscular disease. Handbook of experimental pharmacology 206: 79-101, 2011.

Bolger T.A., Cohen T., Yao T.P: HATs and HDACs. Gene Expression and Regulation (ed. J. Ma), a Current Scientific Frontiers Book. Higher Education Press (Beijing) & Springer, 2005.

Honors and Awards

2012-2017            K99/R00 NIH Pathway to Independence Award           

2009-2011            Association for Frontotemporal Dementias (AFTD) Laden Family Postdoctoral Fellowship

2003-2008            Robert J. Fitzgerald scholar for academic achievements

Teaching Record

Research Teaching/Mentorship:   As a postdoctoral fellow and research associate, I have trained and managed 2 undergraduate students and 4 laboratory technicians that were directly under my supervision. These trainees contributed directly to our research program including scholarly activities such as weekly presentations, figure and manuscript preparations, and organization of grant proposals. 

Reflective Statement

My studies are focused on dissecting the molecular mechanisms underlying neurodegenerative diseases.  We have recently identified specific post-translational modifications, including lysine acetylation, that critically regulate TDP-43 and tau proteins, two major diseased proteins that abnormally accumulate in the brains and spinal cord of Amytotrophic Lateral Sclerosis (ALS) patients as well as various forms of dementia including Alzheimer’s disease (AD).  This work has uncovered new molecular mechanisms that control protein homeostasis in the brain, thus pointing to new avenues for possible therapeutic intervention.   Future work will build off of these basic principles to explore how such post-translational modifications cause protein misfolding and neurodegeneration, which could have significant translational impact.  As an educator, I will teach and mentor students and trainees in molecular, cellular, and biochemical aspects of neurodegerative disease with particular focus on identifying compounds capable of preventing protein aggregation.  I will approach these topics with the creativity and rigor required to make important scientific discoveries and ultimately contribute to the identification of therapies for our aging human population.