Bellen Lab

Paul Marcogliese

Paul Marcogliese

BS and BA, Carleton University, Canada
PhD, University of Ottawa, Canada (David Park)

Research Interests

I am interested in the molecular and cellular mechanisms underlying neurological disease. While the etiology of diseases like Autism Spectrum Disorder (ASD) and Parkinson's disease is complex, the study and identification genes responsible for rare disorders can offer insight into more common conditions. To support the discovery and characterization of novel genes involved in a variety of ill-defined neurological conditions, I am part of the Model Organism Screening Center (MOSC) under the umbrella of the Undiagnosed Diseases Network (UDN). The UDN uses next-generation sequencing (whole-genome and whole-exome) to identify candidate causative gene variant(s) in patients. To support the molecular diagnosis, we use a range of techniques in Drosophila to assess the functional consequences of the patient variant in vivo. Additionally, rapid generation of Drosophila with strong loss of function alleles in these genes provides a phenotyping and screening platform for subsequent mechanistic studies and drug testing. Currently my work is largely focused on elucidating the mechanism underlying IRF2BPL-related neuroregression and associated ASD. Using flies, mice and patient cells, I am employing a multi-systems approach to better understand the function of IRF2BPL.


Marcogliese PC*, Deal SL*, Andrews J*, Harnish JM*, Bhavana VH, Graves HK, Jangam S, Luo X, Liu N, Bei D, Chao YH, Hull B, Lee PT, Pan H, Longley CM, Chao HT, Chung H, Haelterman NA, Kanca O, Manivannan SN, Rossetti LZ, Gerard A, Schwaibold EMC, Guerrini R, Vetro A, England E, Murali CN, Barakat TS, van Dooren MF, Wilke M, van Slegtenhorst M, Lesca G, Sabatier I, Chatron N, Brownstein CA, Madden JA, Agrawal PB, Keller R, Pavinato L, Brusco A, Rosenfeld JA, Marom R, Wangler MF, Yamamoto S (2021) Drosophila functional screening of de novo variants in autism uncovers deleterious variants and facilitates discovery of rare neurodevelopmental diseases. bioRxiv 424813: *Contributed equally. Download PDF.   
Rossetti LZ, Bekheirnia MR, Lewis AM, Mefford HC, Golden-Grant K, Briere LC, Sweetser DA, Walker MA, Kravets E, Stevenson DA, Bruenner G, Sebastian J, Knapo J, Rosenfeld JA, Marcogliese PC, Undiagnosed Diseases Network, Wangler MF (2020) Missense variants in CTNNB1 can be associated with vitreoretinopathy-Seven new cases of CTNNB1-associated neurodevelopmental disorder including a previously unreported retinal phenotype. Molecular Genetics & Genomic Medicine e1542:ePub ahead of print.  [Abstract]
Ravenscroft TA, Janssens J, Lee PT, Tepe B, Marcogliese PC, Makhzami S, Holmes T, Aerts S, Bellen HJ (2020) Drosophila voltage-gated sodium channels are only expressed in active neurons and are localized to distal axonal initial segment-like domains. Journal of Neuroscience 40:7999-8024.  [Abstract]
Dutta D, Briere LC, Kanca O, Marcogliese PC, Walker MA, High FA, Vanderver A, Krier J, Carmichael N, Callahan C, Taft RJ, Simons C, Helman G, Undiagnosed Diseases Network, Wangler MF, Yamamoto S, Sweetser DA, Bellen HJ (2020)  De novo mutations in TOMM70, a receptor of the mitochondrial import translocase, cause neurological impairment. Human Molecular Genetics :Epub ahead of print.  [Abstract]
Chung HL, Mao X, Wang H, Park YJ, Marcogliese PC, Rosenfels JA, Burrage LC, Liu P, Murdock DR, Yamamoto S, Wangler MF, Undiagnosed Diseases Network, Chao HT, Long H, Feng L, Bacino CA, Bellen HJ, Xiao B (2020) De novo variants in CDK19 are associated with a new syndrome with intellectual disability and epileptic encephalopathy. American Journal of Human Genetics 106:717-725.  [Abstract]
Chung HL, Wangler MF, Marcogliese PC, Jo J, Ravenscroft TA, Zuo Z, Duraine L, Sadeghzadeh S, Li-Kroeger D, Schmidt RE, Pestronk A, Rosenfeld JA, Burrage L, Herndon MJ, Chen S, Undiagnosed Diseases Network, Shillington A, Vawter-Lee M, Hopkin R, Rodriguez-Smith J, Henrickson M, Lee B, Moser AB, Jones RO, Watkins P, Yoo T, Mar S, Choi M, Bucelli RC, Yamamoto S, Lee HK, Prada CE, Chae JH, Vogel TP, Bellen HJ (2020) Loss or gain of function mutations in ACOX1 cause axonal loss via different mechanisms. Neuron 106:589-606.  [Abstract]
Guo H*, Bettella E*, Marcogliese PC*, Zhao R, Andrews JC, Nowakowski TJ, Gillentine MA, Hoekzema K, Wang T, Wu H, Jangam S, Liu C, Ni H, Willemsen MH, van Bon BW, Rinne T, Stevens SJC, Kleefstra T, Brunner HG, Yntema HG, Long M, Zhao W, Hu Z, Colson C, Richard N, Schwartz CE, Romano C, Castiglia L, Bottitta M, Dhar SU, Erwin DJ, Emrick L, Keren B, Afenjar A, Zhu B, Bai B, Stankiewicz P, Herman K; University of Washington Center for Mendelian Genomics, Mercimek-Andrews S, Juusola J, Wilfert AB, Abou Jamra R, Büttner B, Mefford HC, Muir AM, Scheffer IE, Regan BM, Malone S, Gecz J, Cobben J, Weiss MM, Waisfisz Q, Bijlsma EK, Hoffer MJV, Ruivenkamp CAL, Sartori S, Xia F, Rosenfeld JA, Bernier RA, Wangler MF, Yamamoto S, Xia K, Stegmann APA, Bellen HJ, Murgia A, Eichler EE (2019) Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders. Nature Communications 10:4679. (*equal contribution) [Abstract]
Ansar M, Chung HL, Al-Otaibi A, Elagabani MN, Ravenscroft TA, Paracha SA, Scholz R, Abdel Magid T, Sarwar MT, Shah SF, Qaisar AA, Makrythanasis P, Marcogliese PC, Kamsteeg EJ, Falconnet E, Ranza E, Santoni FA, Aldhalaan H, Al-Asmari A, Faqeih EA, Ahmed J, Kornau HC, Bellen HJ, Antonarakis SE (2019) Bi-allelic variants in IQSEC1 cause intellectual disability, developmental delay and short stature. American Journal of Human Genetics 105:907-920.  [Abstract]
Shutinoski B, Hakimi M, Harmsen IE, Lunn M, Rocha J, Lengacher N, Zhou YY, Khan J, Nguyen A, Hake-Volling Q, El-Kodsi D, Li J, Alikashani A, Beauchamp C, Majithia J, Coombs K, Shimshek D, Marcogliese PC, Park DS, Rioux JD, Philpott DJ, Woulfe JM, Hayley S, Sad S, Tomlinson JJ, Brown EG, Schlossmacher MG (2019) Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner. Science Translational Medicine 11:eaas9292.  [Abstract]
Yang J, Kim KS, Iyirhiaro GO, Marcogliese PC, Callaghan SM, Qu D, Kim WJ, Slack RS, Park DS (2019) DJ-1 modulates the unfolded protein response and cell death via upregulation of ATF4 following ER stress. Cell Death & Disease 10:135.  [Abstract]
Lin G, Wang L, Marcogliese PC, Bellen HJ (2018) Sphingolipids in the pathogenesis of Parkinson's disease and parkinsonism. Trends in Endocrinology & Metabolism 30:106-117.  [Abstract]
Marcogliese PC*, Shashi V*, Spillmann RC, Stong N, Rosenfeld JA, Koenig MK, Martínez-Agosto JA, Herzog M, Chen AH, Dickson PI, Lin HJ, Vera MU, Salamon N, Graham JM Jr, Ortiz D, Infante E, Steyaert W, Dermaut B, Poppe B, Chung HL, Zuo Z, Lee PT, Kanca O, Xia F, Yang Y, Smith EC, Jasien J, Kansagra S, Spiridigliozzi G, El-Dairi M, Lark R, Riley K, Koeberl DD, Golden-Grant K; Program for Undiagnosed Diseases (UD-PrOZA); Undiagnosed Diseases Network, Yamamoto S, Wangler MF, Mirzaa G, Hemelsoet D, Lee B, Nelson SF, Goldstein DB, Bellen HJ, Pena LDM (2018) IRF2BPL is associated with neurological phenotypes. American Journal of Human Genetics 103:245-260. (*equal contribution) [Abstract]
Kim KS*, Marcogliese PC*, Yang J, Callaghan S, Resende V, Abdel-Messih E, Marras C, Visanji NP, Huang J, Schlossmacher MG, Trinkle-Mulcahy L, Slack RS, Lang AE, Canadian Lrrk2 in Inflammation Team (CLINT), Park DS (2018) Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson's disease. Proceedings of the National Academy of Sciences USA 115:E5164-E5173. (*equal contribution) [Abstract]
Marcogliese PC, Wangler MF (2018) Drosophila as a model for human diseases. eLS 1:22 Jan 2018. [Article] 
Marcogliese PC, Abuaish S, Kabbach G, Abdel-Messih E, Seang S, Li G, Slack RS, Haque ME, Venderova K, Park DS (2017) LRRK2(I2020T) functional genetic interactors that modify eye degeneration and dopaminergic cell loss in DrosophilaHuman Molecular Genetics 26:1247-1257.  [Abstract]
Qu D, Hage A, Don-Carolis K, Huang E, Joselin A, Safarpour F, Marcogliese PC, Rousseaux MW, Hewitt SJ, Huang T, Im DS, Callaghan S, Dewar-Darch D, Figeys D, Slack RS, Park DS (2015) BAG2 gene-mediated regulation of PINK1 protein is critical for mitochondrial translocation of PARKIN and neuronal survival. Journal of Biological Chemistry 290:30441-30452.  [Abstract]
Sanchez G, Varaschin RK, Büeler H, Marcogliese PC, Park DS, Trudeau LE (2014) Unaltered striatal dopamine release levels in young Parkin knockout, Pink1 knockout, DJ-1 knockout and LRRK2 R1441G transgenic mice. PLoS One 9:e94826.  [Abstract]
Rousseaux MW, Marcogliese PC, Qu D, Hewitt SJ, Seang S, Kim RH, Slack RS, Schlossmacher MG, Lagace DC, Mak TW, Park DS (2012) Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proceedings of the National Academy of Sciences USA 109:15918-15923.  [Abstract]
Aleyasin H, Rousseaux MW, Marcogliese PC, Hewitt SJ, Irrcher I, Joselin AP, Parsanejad M, Kim RH, Rizzu P, Callaghan SM, Slack RS, Mak TW, Park DS (2010) DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. Proceedings of the National Academy of Sciences USA 107:3186-3191.  [Abstract]

Last Modified 3-31-21 by Jodie Hebert

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