RESEARCH SUMMARY

My lab utilizes a combined approach of molecular genetics, biochemistry, and cell biology to explore mechanisms of neuropathology using mouse models of Huntington Disease, a neurodegenerative disorder caused by expansion of a glutamine-encoding CAG triplet repeat in the Huntingtin gene. The Huntingtin gene is required for normal brain development and maintenance of neuronal function, but its specific actions that contribute to these roles are unknown. We aim to define the mechanisms of neurotoxicity and understand the basis of selective neuropathology, by characterizing the molecular function of Huntingtin under both normal and pathological conditions.

SELECTED PUBLICATIONS

Bowman AB, Lam YC, Jafar-Nejad P, Chen HK, Richman R, Samaco RC, Fryer JD, Kahle JJ, Orr HT, Zoghbi HY. Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. 2007. Nature Genetics. 39(3): 373-379.

*Lam YC, *Bowman AB, Jafar-Nejad P, Lim J, Richman R, Fryer JD, Hyun E, Duvick LA, Orr HT, Botas J, Zoghbi HY. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. 2006. Cell. 127(7): 1335-1347. * denotes co-first authorship.

Helmlinger D, Hardy S, Abou-Sleymane G, Eberlin A, Bowman AB, Gansmuller A, Picaud S, Zoghbi HY, Trottier Y, Tora L, Devys D. Polyglutamine-expanded Ataxin-7 Mediates Aberrant Recruitment of TFTC-type Complexes and Chromatin Decondensation Leading to Photoreceptor Dysfunction in Spinocerebellar Ataxia Type 7. 2006. PLoS Biology. 4(3): e67.

Bowman AB, Yoo SY, Dantuma NP, Zoghbi HY. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation. 2005. Human Molecular Genetics. 14(5): 679-691.

Young JI, Hong EP, Castle JC, Crespo-Barreto J, Bowman AB, Rose MF, Kang D, Richman R, Johnson JM, Berget S, Zoghbi HY. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. 2005. Proceedings of the National Academy of Sciences. 102(49): 17551-17558.

Bowman AB, Levorse JM, Ingram RS, and Tilghman SM. Functional Characterization of a Testis-Specific DNA Binding Activity at the H19/Igf2 Imprinting Control Region. 2003. Molecular and Cellular Biology. 23(22): 8345-8351.

Bowman AB, Kamal A, Ritchings BW, Philp AV, Mcgrail M, Gindhart J, and Goldstein LSB. Kinesin Dependent Axonal Transport is Mediated by the Sunday Driver (SYD) Protein. 2000. Cell. 103: 583-594.