Like tau acetylation and phosphorylation in Alzheimer’s Disease, TDP-43 modifications similarly promote aberrant pathology seen in diseased brain and spinal cord of ALS and FTLD-TDP patients. Understanding such post-translational mechanisms could lead to better therapeutic avenues to pursue for ALS, FTD and other diseases characterized by TDP-43 pathology.
Although distinct, many of these diseases share common underlying pathogenic mechanisms. We seek to uncover the molecular pathways that promote protein aggregation and the formation of amyloid deposits that cause neurodegeneration and cognitive impairments.
Using a combination of biochemistry, genetics, and cell biology, we have identified several post-translational mechanisms including lysine acetylation, phosphorylation, and cysteine disulfide modifications that critically regulate many disease-associated proteins in the brain including the tau protein in AD and the TDP-43 protein present in ALS and FTLD patients. We have pioneered the concept that lysine acetylation, in particular, is an unanticipated, yet critical modification that promotes the evolution and maturation of pathological aggregates in a spectrum of neurodegenerative diseases.
This raises the intriguing possibility of modification-targeted therapeutics to combat normal ageing mechanisms and a broad range of neurodegenerative diseases. Ultimately, by uncovering the mechanistic details that regulate normal and aberrant protein functions in the diseased brain, can we begin to uncover the molecular platform for future drug-based therapies against these debilitating diseases.
Relevance:
Although clinically and pathologically distinct, the disorders shown below share a common underlying pathogenic mechanism in which normally soluble proteins become abnormally sequestered into protein aggregates that can exert toxic loss and gain of functions in a tissue-specific manner.
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Ping Wang, Connor Wander, Chao-Xing Yuan, Michael Bereman, and Todd Cohen
With many more to come!
Celebrating publications is a tradition in the scientific community. In Todd Cohen’s words, “Research isn’t all that gratifying. You work for years in the lab about something nobody knows about and finally submit a paper… months later it hopefully gets accepted. You have to take the opportunity to celebrate”. (Or he said something similar).
There are no upcoming events at this time.
Welcome to the new website for Todd Cohen’s Lab at UNC Chapel Hill! We will be incrementally moving our online presence to this web address. You can find our old googlesites website here.
This is the digital home for Todd Cohen’s lab in the Department of Neurology at UNC Chapel Hill, not to be confused with Jessica Cohen’s Lab from Psychology and Neuroscience!
Learn more about the research being done in the Todd Cohen Lab at UNC Chapel Hill here.
This website will provide us with a unique platform for discussion and public interaction. The forum section of the website is under construction, but check back soon! Any burning questions for Todd Cohen’s Lab at UNC can be asked here.
Stay tuned for more updates! Any feedback is appreciated as well! Leave a comment below and tell us what you think.
Connor graduated from Virginia Tech with a B.S. in Biology and Biochemistry in 2014, and joined the lab as a technician for two years. He then joined the Cohen and Song Labs as a graduate student where he studied astrocytes and inhibitory networks in Alzheimer’s Disease. Connor runs a science communication podcast and website, Straight from a Scientist (SFS). Currently, Connor studies model systems for cerebrovascular disease in the context of plasma biology at Alkahest, Inc in San Carlos, CA. Outside of the lab, he enjoys hiking, swimming, graphic design, gaming, Brazilian Jiu Jitsu, paintball and caring for his bearded dragons.
Hanna is a fifth year PhD candidate and NSF-GRFP fellow. She received a B.S. in Biochemistry (and minor in Spanish Language) from Oakland University in Michigan, where she was an undergraduate research assistant in Dr. Sanela Martic’s biochemistry laboratory investigating the misfolding and aggregation of the tau protein. After, she joined the Biological and Biomedical Sciences Program, the department of Biochemistry and Biophysics, and the Cohen lab at the University of North Carolina at Chapel Hill. She has been investigating many facets of tau protein biochemistry.
Vanya is an undergraduate student at UNC Chapel Hill majoring in Neuroscience and minoring in Medical Anthropology. She hopes to practice medicine and continue studying neurodegenerative disease in the future. Throughout her time in the Cohen lab, she has examined corpora amylacea in the hippocampus in regard to Alzheimer’s Disease and is currently observing how environmental factors affect ALS pathology. Outside of lab, Vanya enjoys reading, baking, and hiking.
Carli is a fourth-year Ph.D. candidate in the Neuroscience curriculum. Before coming to UNC for graduate studies, Carli received a B.S. in Cellular and Molecular Biology at California State University, Northridge. She worked with Dr. Randy Cohen studying the neurodegeneration of Purkinje cells from excitotoxicity by GABA receptor activation in an ataxic rat model. After graduating in May 2015, Carli joined Dr. Daniel Geschwind’s lab at UCLA as a staff research associate where she investigated the effects of overexpression of specific genes known to be involved in neurogenesis such as NGN2, FGFR2, and SOX5 in primary human neural progenitor cells. Now in Todd Cohen’s lab at UNC Chapel Hill, Carli is evaluating the role of a particular post translational modification, tau cleavage by caspases, and its implications to Alzheimer’s disease. Outside of the lab, she enjoys baking, hanging out with her cat, running, eating cheese and making craft cocktails.
