Mark Labow, PhD
(Co-Mentor: Michael Schebesta, PhD)
Chemical Biology & Therapeutics
Cambridge, Massachusetts, United States
Functional genomics approaches have become powerful tools for comprehensive identification of regulators of key physiologic and pathologic processes. Our group has focused on combining new technologies and biology to discover a number of novel genes regulating signal transduction downstream of the second messengers calcium and cAMP. Currently our group is focused on utilizing genome-scale functional screening approaches to understand mechanisms regulating the transcription and translation of toxic microsatellite-repeat containing RNAs that cause a variety of devastating neurodegenerative and neuromuscular diseases. Such large microsatellite expansions produce RNAs that can affect RNA metabolism by acting as sinks for RNA-binding proteins, inhibiting RNA splicing or microRNA production. Most recently such RNAs have also been shown to engage in a unique form of ATG-independent translation that requires secondary structure endowed by the repeats, resulting in production of highly toxic mono- and di-peptide polyproteins. Little is known about how levels of repeat RNAs or their translation are regulated. Our group is developing systems to study the metabolism and effects of these repeat RNAs as well as utilizing iPS technologies to scale production of terminally-differentiated cells affected in disease.
TMEM203 is a novel regulator of intracellular calcium homeostasis and is required for spermatogenesis.
Shambharkar P, Bittinger MA, Latario B, Xiong Z, Bandyopadhyay S, Davis V, Lin V, Yang Y, Valdez R, Labow MA.
PLoS One. 2015 May 21;10(5):e0127480.
The tyrosine kinase BMX is an essential mediator of inflammatory arthritis in a kinase-independent manner.
Gottar-Guillier M, Dodeller F, Huesken D, Iourgenko V, Mickanin C, Labow M, Gaveriaux S, Kinzel B, Mueller M, Alitalo K, Littlewood-Evans A, Cenni B.
J Immunol, 2011, May 15;186(10):6014-23.
Activation of cAMP response element-mediated gene expression by regulated nuclear transport of TORC proteins.
Bittinger MA, McWhinnie E, Meltzer J, Iourgenko V, Latario B, Liu X, Chen CH, Song C, Garza D, Labow M.
Curr Biol. 2004 Dec 14;14(23):2156-61.
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