BETTER UNDERSTANDING THE MECHANISMS OF NEURODEGENERATIVE DISEASE

PUBLICATIONS           

            Research Publications:

1.     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

2.    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.

3.     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

4.       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

5.   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

6.     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

7.   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

8.     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

9.     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

10.  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.

11.  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.

12.  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:

1.     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

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

 

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

            Book Chapters

1.   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.

2.     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.