Neurological disease: it's not just about genes anymore

Date: 

Tuesday, 7 July, 2020

He took his Phd at TIGEM in Italy, in the lab of Sandro Banfi, working in the microRNA field. He developed two important predictors: HOCTAR (Genome Research, 2009) and CoMeTa (Genome Research, 2012), whose prediction accuracy reaches nearly 100%. CoMeTa was the first tool to infer the biological pathways of each human miRNA based on the identification of its set of target genes. HOCTAR led to the discovery of the function of miR-128, which controls the master gene TFEB (Science, 2009).

After the PhD he started to become interested in neuroscience and joined the laboratory of Prof. Huda Zoghbi at the Baylor College of Medicine for his postdoc. Here he studied the regulation of the epigenetic factor MECP2 during neurodevelopment (Genes & Development, 2013) and the post-translational modification of Ataxin1, a protein involved in neurodegenerative disease (Cell, 2015 and Cell, 2018).

He is now assistant Professor at the Columbia University and his lab focuses on the following aspects:

- RNA-binding proteins and non-coding RNA regulatory networks in neurological disorders
- Establishment and maintenance of RNA homeostasis in the brain
- Development of RNA therapeutic approaches to neurological diseases
- Protein dosage and neurological disorders

https://www.genetics.cumc.columbia.edu/profile/vincenzo-gennarino-phd

Selected publications:

Gennarino VA, Palmer EE, McDonell LM, Wang L, Adamski CJ, Koire A, See L, Chen CA, Schaaf CP, Rosenfeld JA, Panzer JA, Moog U, Hao S, Bye A, Kirk EP, Stankiewicz P, Breman AM, McBride A, Kandula T, Dubbs HA, Macintosh R, Cardamone M, Zhu Y, Ying K, Dias KR, Cho MT, Henderson LB, Baskin B, Morris P, Tao J, Cowley MJ, Dinger ME, Roscioli T, Caluseriu O, Suchowersky O, Sachdev RL, Lichtarge O, Tang J, Boycott KM, Holder JL, and Zoghbi HY.
A mild PUM1 mutation is associated with adult-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures.
Cell, 2018 Feb 22;172(5):924-936e.11.

Gennarino VA, Alcott CA, Chen CA, Chaudhury A, Rosenfeld JA, Parikh S, Wheless JW, Roeder ER, Horovitz DDG, Roney EK, Smith JL, Cheung SW, Li W, Nailson JR, Schaaf CP, Zoghbi HY.
NUDT21-spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance via alternative polyadenylation.
eLife, 2015 Aug 27;4. doi: 10.7554/eLife.10782.

Gennarino VA, Singh RK, White JJ, De Maio A, Han K, Kim JY, Jafar-Nejad P, di Ronza A, Kang H, Sayegh LS, Cooper TA, Orr HT, Sillitoe RV and Zoghbi HY.
Pumilio1 Haploinsufficiency Leads to SCA1-like Neurodegeneration by Increasing Wild-Type Ataxin1 Levels.
Cell, 2015 Mar 12;160(6):1087-98.

Han K, Gennarino VA, Lee Y, Pang K, Hashimoto-Torii K, Choufani S, Raju CS, Oldham MC, Weksberg R, Rakic P, Liu Z, and Zoghbi HY.
Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p.
Genes & Development, 2013 Mar 1;27(5):485-90.

Gennarino VA, D'angelo G, Dharmalingam G, Fernandez S, Russolillo G, Sanges R, Mutarelli M, Belcastro V, Ballabio A, Verde P, Sardiello M, Banfi S.
Identification of microRNA-regulated gene networks by expression analysis of target genes.
Genome Research, 2012 Jun;22(6):1163-72. Epub 2012 Feb 24.

Gennarino VA, Sardiello M, Avellino R, Meola N, Maselli V, Anand S, Cutillo L, Ballabio A and Banfi S.
MicroRNA target prediction by expression analysis of host genes.
Genome Research, 2009 Mar;19(3):481-90.