Areas of Interest
Research in the Bielas lab is aimed at understanding the epigenetic and molecular mechanisms of stem cell multipotency, self-renewal and neurogenesis required to build a brain. We develop these project from our human genetic studies aimed at identifying the genetic basis of neurodevelopmental disorders. A major challenge to investigating cell and molecular mechanisms of neurodevelopmental disorders has been the lack of affected tissue. To address this problem we use human brain organoid cultures, differentiated from human pluripotent stem cells (hPSCs) and transgenic mice as model systems. Our goal is to elucidate the pathology of clinically important neurological disorders and novel features of human brain development.
Published Articles or Reviews
KC R , Srivastava A, Wilkowski JM , Burke DT , Bielas SL. Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation-detection. Sci Rep. 2016 Aug 25;6:32048.
Harding B, Moccia A, Soukarieh O, Drunat S, Chitty L, Verloes A, Gressens P, El Ghouzzi V, Joriot S, Passemard S, Martins A, Di Cunto F, Bielas SL. Mutations in Citron-Kinase cause recessive micro-lissencephaly with multinucleated neurons. Am J Hum Genet. 2016 Aug 4;99(2):511-20.
Li H, Bielas SL, Zaki MS, Ismail S, Farfara D, Um K, Rosti RO, Scott EC, Tu S, Chi NC, Gabriel S, Gunel M, Gleeson JG. Biallelic mutations in the kinase domain of citron link mitotic cytokinesis to human primary microcephaly. Am J Hum Genet. 2016 Aug 4;99(2):501-10.
Hebbarm M, Prasada H, Bhowmik AD, Trujillano D, Shukla A, Chakraborti S, Kandaswamy KK, Rolfs A, Kamath N, Dalal A, Bielas S, Girisha KM. Homozygous deletion of exons 2 and 3 of NPC2 associated with Niemann-Pick disease type C. Am J Med Genet A. 2016 Sep;170(9):2486-9.
Shukla A, Upadhyai P, Shah J, Neethukrishna K, Bielas S, Girisha KM. Autosomal recessive spinocerebellar ataxia 20: Report of a new patient and review of literature. Eur J of Med Genet. 2016 Nov 29. 2016.
Srivastava A, KC R, Tsan YC, Liao R, Su F, Cao X, Hannibal MC, Keegan CE, Chinnaiyan AM, Martin DM, Bielas SL. De Novo dominant ASXL3 mutations alter H2A deubiquitination and transcription in Bainbridge-Ropers syndrome. Hum. Mol. Genet. Dec 8, 2015.
Baek ST, Kerjan G, Bielas SL, Lee JE, Fenstermaker AG, Novarino G, Gleeson JG. Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous microRNA dysregulation. Neuron. 2014 Jun 18;82(6):1255-62.
Lee JH, Silhavy JL, Lee JE, Al-Gazali L, Thomas S, Davis EE, Bielas SL, Hill KJ, Iannicelli M, Brancati F, Gabriel SB, Russ C, Logan CV, Sharif SM, Bennett CP, Abe M, Hildebrandt F, Diplas BH, Attié-Bitach T, Katsanis N, Rajab A, Koul R, Sztriha L, Waters ER, Ferro-Novick S, Woods CG, Johnson CA, Valente EM, Zaki MS, Gleeson JG. Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science. 2012 Feb 24;335(6071):966-9.
Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, Lehle L, Hombauer H, Adamowicz M, Swiezewska E, De Brouwer AP, Blümel P, Sykut-Cegielska J, Houliston S, Swistun D, Ali BR, Dobyns WB, Babovic-Vuksanovic D, van Bokhoven H, Wevers RA, Raetz CR, Freeze HH, Morava E, Al-Gazali L, Gleeson JG. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010 Jul 23;142(2):203-17.
Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti RO, Kayserili H, Swistun D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field SJ, Gayral S, Jacoby M, Schurmans S, Dallapiccola B, Majerus PW, Valente EM, Gleeson JG. Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat Genet. 2009 Sep;41(9):1032-6.
Bielas SL, Serneo FF, Chechlacz M, Deerinck TJ, Perkins GA, Allen PB, Ellisman MH, Gleeson JG. Spinophilin facilitates dephosphorylation of doublecortin by PP1 to mediate microtubule bundling at the axonal wrist. Cell. 2007 May 4;129(3):579-91.