Chair, Biomedical Sciences
The combined long-term objectives of our research are to better understand the molecular, genetic, and cellular mechanisms causing neurodevelopmental and neurological disorders. Overall, my research interests lie primarily in the study of disorders of brain development and neurological disease, and specifically involve the following areas of investigation:
1) functional analyses of AHI1 and CSPP1, two novel genes which we mapped and cloned in individuals with Joubert syndrome (Ferland et al., Nature Genetics, 2004; Doering et al., J. Comp. Neurol., 2008; Hsiao et al., Hum. Mol. Genet., 2009; Westfall et al., J. Neurosci., 2010; Tuz et al., J. Biol. Chem., 2013; Tuz et al., Am. J. Hum. Genet., 2014; Bourgeois and Ferland, Dev. Biol., 2019; Munoz and Ferland, J. Cell Sci., 2019; Hsiao et al., J. Neurosci., 2021),
2) formation and function of the primary non-motile cilia in development and disease (Hsiao et al., Hum. Mol. Genet., 2009; Westfall et al., J. Neurosci., 2010; Hsiao et al., Cilia, 2012; Tuz et al., J. Biol. Chem., 2013; Tuz et al., Am. J. Hum. Genet., 2014; Hua and Ferland, Cilia, 2017; Hua and Feland, Cell. Mol. Life Sci., 2018; Hua and Ferland, Bioessays, 2018; Bourgeois and Ferland, Dev. Biol., 2019; Munoz and Ferland, J. Cell Sci., 2019; Hsiao et al., J. Neurosci., 2021),
3) genetic and neuroanatomical mechanisms of seizure threshold, seizure propagation, epileptogenesis, and Sudden Unexplained Death in Epilepsy (SUDEP) (Ferland et al., G3 Genes, Genom. Genet, 2017; Ferland, 2017; Loscher, Ferland, and Ferraro, Epilepsy and Behavior, 2017; Kadiyala et al., J. Neurosci., 2016; Kadiyala et al., Epil. Res., 2015; Kadiyala et al., PLoS ONE, 2014; Papandrea et al., Exp. Neurol., 2009; Papandrea et al., Epil. Res., 2009; Ferland et al, 1998a,b,c, 1999, 2002a,b, 2003).
Harvard Medical School & Howard Hughes Medical Institute (Boston, Massachusetts)
Hsiao YC, Muñoz-Estrada J, Tuz K, Ferland RJ. The transition zone protein AHI1 regulates neuronal ciliary trafficking of MCHR1 and its downstream signaling pathway. J. Neurosci., 41(17):3932-3943, 2021.
- Article was chosen as 1 of two Featured Articles in the Journal of Neuroscience (with accompanying write-up)
Srinivasan A, Srinivasan A, Ferland RJ. AutoSholl allows for automation of Sholl analysis independent of user tracing. J Neurosci Methods, 331:1-6, 2020. Source code & compiled version of the algorithm are available at: https://github.com/ferlandlab/AutoSholl
Bourgeois JR and Ferland RJ. Loss of the neurodevelopmental Joubert syndrome causing protein, Ahi1, causes motor and muscle development delays independent of central nervous system involvement. Developmental Biology, 448(1): 36-47, 2019.
- This work was highlighted in F1000Prime, 5 Dec, 2018.
Kaskow BJ, Buttrick TS, Klein H-U, White C, Bourgeois JR, Ferland RJ, Patsopoulos N, Bradshaw EM, De Jager PL, Elyaman W. Multiple sclerosis AHI1 genetic risk promotes IFNγ+ CD4+ T cells. Neurology: Neuroimmunology & Neuroinflammation, 5 (1): 1-10 (e414), 2018.
Srinivasan A, Muñoz-Estrada J, Bourgeois JR, Nalwalk J, Pumiglia K, Sheen V, Ferland RJ. BranchAnalysis2D/3D automates morphometry analyses of branching structures. J Neurosci Methods, 294:1-6, 2018. Source code & compiled version of the algorithm are available at: https://github.com/ferlandlab/BranchAnalysis2D-3D
Ferland RJ, Smith J, Papandrea D, Gracias J, Haines L, Kadiyala SB, O'Brien B, Kang EY, Beyer B, Herron BJ. Multidimensional genetic analysis of repeated seizures in the hybrid mouse diversity panel reveals a novel epileptogenesis susceptibility locus. G3 Genes Genom. Genet., 7(8): 2545-2558, 2017.
Kadiyala SB, Yannix JQ, Nalwalk JW, Papandrea D, Beyer BS, Herron BJ, Ferland RJ. Eight flurothyl-induced generalized seizures lead to the rapid evolution of spontaneous seizures in mice: a model of epileptogenesis with seizure remission. J. Neurosci., 36(28): 7485-7496, 2016.
Kadiyala SB, Papandrea D, Tuz K, Anderson TM, Jayakumara S, Herron BJ, Ferland RJ. Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity. Epilepsy Res., 109:183-196, 2015.
Hu J, Lu J, Lian G, Ferland RJ, Dettenhofer M, Sheen VL. Formin 1 and Filamin B physically interact to coordinate chondrocyte proliferation and differentiation in the growth plate. Hum. Mol. Genet., 23(17):4663-4673, 2014.
Tuz K, Bachmann-Gagescu R, O'Day DR, Hua K, Isabella CR, Phelps IG, Stolarski AE, O'Roak BJ, Dempsey JC, Lourenco C, Alswaid A, Bönnemann CG, Medne L, Nampoothiri S, Stark Z, Leventer RJ, Topçu M, Cansu A, Jagadeesh S, Done S, Ishak GE, Glass IA, Shendure J, Neuhauss SC, Haldeman-Englert CR, Doherty D, Ferland RJ. Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. Am. J. Hum. Genet., 94(1): 62–72, 2014.
Tuz K, Hsiao YC, Juarez O, Shi B, Harmon EY, Phelps IG, Lennartz MR, Glass IA, Doherty D, Ferland RJ. The Joubert syndrome associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions. J. Biol. Chem., 288(19):13676-94, 2013.
Bhoiwala DL, Koleilat I, Qian J, Beyer B, Hushmendy SF, Mathew A, Bhoiwala DL, Ferland RJ, Crawford DR. Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment. Neurol. Res., 35(1):79-89, 2013.
Zhang J, Neal J, Lian G, Shi B, Ferland RJ, Sheen VL. Brefeldin A-inhibited guanine exchange factor 2 regulates Filamin A phosphorylation and neuronal migration. J. Neurosci., 32(36):12619-12629, 2012.
Lian G, Lu J, Hu J, Zhang J, Cross SH, Ferland RJ, Sheen VL. Filamin A Regulates Neural Progenitor Proliferation and Brain Size through Wee1-Dependent Cdk1 Phosphorylation. J. Neurosci., 32(22):7672-84, 2012.
Westfall (Doering) JE, Hoyt C, Liu Q, Hsiao Y-C, Pierce EA, Page-McCaw PS, Ferland RJ. Retinal degeneration and failure of photoreceptor outer segment formation in mice with targeted deletion of the Joubert syndrome gene, Ahi1. J. Neurosci., 30(26):8759-8768, 2010.
Hsiao Y-C, Tong ZJ, Westfall (Doering) JE, Ault JG, Page-McCaw PS, Ferland RJ. Ahi1, whose human ortholog is mutated in Joubert syndrome, is required for proper localization of Rab8a, ciliogenesis, and vesicular trafficking. Hum. Mol. Genet., 18(20):3926-3941, 2009.
Ferland RJ, Batiz LF, Neal J, Lian G, Bundock E, Lu J, Hsiao Y-C, Diamond R, Mei D, Banham A, Brown PJ, Vanderburg CR, Joseph J, Hecht JL, Folkerth R, Guerrini R, Walsh CA, Rodriguez EM, Sheen VL. Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia. Hum. Mol. Genet., 18(3):497-516, 2009.
Morrow EM, Yoo S-Y, Flavell SW, Kim T-K, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A, Al-Saad S, Ware J, Joseph RM, Greenblatt R, Gleason D, Ertelt JA, Apse KA, Bodell A, Partlow JN, Barry B, Yao H, Markianos K, Ferland RJ, Greenberg ME, Walsh CA. Identifying autism loci and genes by tracing recent shared ancestry. Science, 321:218-223, 2008.
- This work was highlighted in F1000 Prime, 31 Jul 2008.
Doering JE, Kane K, Hsiao Y-C, Yao C, Shi B, Slowik A, Dhagat B, Scott D, Ault JG, Page-McCaw PS, Ferland RJ. Species differences in the expression of AHI1, a protein implicated in the neurodevelopmental disorder Joubert syndrome, with preferential accumulation to stigmoid bodies. J. Comp. Neurol., 511:238-256, 2008.
Ferland RJ, Eyaid W, Collura RV, Tully LD, Hill RS, Al-Nouri D, Al-Rumayyan A, Topcu M, Gascon G, Bodell A, Shugart YY, Ruvolo M, and Walsh CA. Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert Syndrome. Nature Genet., 36:1008-1013, 2004.
Other scholarly activity
Löscher W, Ferland RJ, Ferraro TN. Strain effects on expression of seizures and epilepsy. In: Models of Seizure and Epilepsy, 2nd edition, Cambridge: Academic Press (2017) pp. 21-38. ISBN 9780128040669
Hua K, Bourgeois JR, Ferland RJ. Joubert syndrome. In: Reference Module in Neuroscience and Biobehavioral Psychology, Elsevier (2017) pp. 1-8. ISBN 9780128093245
Ferland RJ, Walsh CA. The genetics of Joubert syndrome: Insights into the development of the posterior midline of the brain. In: Squire, LR (Ed.) Encyclopedia of Neuroscience. San Diego: Academic Press (2009) pp. 249-256.
Applegate CD, Burchfiel JL, Ferland RJ, Nierenberg J. The role of rhinencephalic networks in the late stages of kindling. In: Corcoran, M and Moshe, S (Eds.) Kindling 5. New York: Raven Press (1998) pp. 151-165.
Ferland RJ and Guerrini R. Nodular heterotopia is built upon layers. Neurology, 73: 742-743, 2009.
Ferland R and Hua K. Referee Report For: Murine Cep290 phenotypes are modified by genetic backgrounds and provide an impetus for investigating disease modifier alleles [version 1; referees: 2 approved] F1000Research 2015, 4:590 (doi: 10.5256/f1000research.7495.r10185)
Hua K and Ferland RJ. Primary cilia: the story of the hair-like organelle that signals just became more complicated. Atlas of science, 2019. https://atlasofscience.org/primary-cilia-the-story-of-the-hair-like-organelle-that-signals-just-became-more-complicated/