Prof. Shen is leading a research group working on animal model and human induced pluripotent stem cell (iPSC) models of brain disorders at REMEDI, School of Medicine, NUI Galway. His team has collaborated with Irish clinicians and now generated iPSCs from a total of 88 individuals of healthy controls, and patients with Autistic Spectrum Disorders (ASD), Epilepsy, Fragile X Syndrome (FXS), Amyotrophic Lateral Sclerosis (ALS), Retinitis Pigmentosa (RP), and Long QT syndrome (LQTS), all of which are associated with specific genetic lesions. They are currently differentiating the iPSCs into astrocytes, neurons and cardiomyocytes, and phenotype them to establish human disease models on dish. They also discovered that ULK4 can be a rare risk factor for neurodevelopmental and neuropsychiatric disorders. They are working on the Ulk4 hypomorph mouse model and discovered its role in neuritogenesis, neurogenesis, ciliogenesis and anxiety behavior. Their recent Public - No restrictionations include: 1. Liu M, Fitzgibbon M, Wang Y. Reilly J, Qian X, OBrien T, Clapcote S, Shen S*, Roche M *. Ulk4 regulates GABAergic signaling and anxiety-related behavior. Transl. Psych . (2018) 8:43. 2. Liu M, Xu P, Guan ZL, Qian X, Dockery P, , Fitzgerald U, OBrien T, Shen S*. Ulk4 deficiency leads to hypomyelination in mice. GLIA, 2018 Jan;66(1):175-190. 3. Madill M, McDonagh K, Ma J, Vajda A, McLoughlin P, OBrien T, Hardiman O, Shen S*. Amyotrophic Lateral Sclerosis patient iPSC-derived astrocytes impair autophagy via non-cell autonomous mechanisms. Mol. Brain . 2017 Jun 13;10(1):22. 4. Sotthibundhu A, McDonagh K, Klawiter A, Thompson K, Dockery P, Devine M, Kunath T, OBrien T, Barry F, Shen S*. 2016. Rapamycin Regulates Autophagy and Cell Adhesion in Induced Pluripotent Stem Cells. Stem Cell Res. Ther . 2016 Nov 15;7(1):166. 5. Liu M, Guan Z, Shen Q, Flinter F, Domínguez L, Ahn JW, Collier DA, OBrien T, Shen S*. Ulk4 Regulates Neural Stem Cell Pool. Stem Cells. 2016 Sep;34(9):2318-31. 6. Liu M, Guan ZL, Shen Q, Lalor P, Fitzgerald U, OBrien T, Dockery P, Shen S*. Ulk4 is essential for ciliogenesis and CSF flow. 2016, J Neurosci. 2016 Jul 20;36(29):7589-600. 7. Dominguez L, Schlosser G; Shen S*. 2015. Expression of a novel serinethreonine kinase gene, Ulk4 , in neural progenitors during Xenopus laevis forebrain development. Neuroscience, 2015 Apr 2;290:61-79. 8. Lang B, Pu J, Hunter I, Liu M, Martin-Granados C, Reilly TJ, Gao GD, Guan ZL, Li W, Shi Y, He G, He L, Stefánsson H, St Clair D, Blackwood DH, McCaig CD, Shen S*. 2014 Recurrent deletions of ULK4 in schizophrenia: a novel gene crucial for neuronal elongation, branching and motility J Cell Sci 127:630-40.

Modeling neurological diseases in mice and in human pluripotent stem cells for understanding gene function, disease pathologiesmechanisms and for drug discovery.KEY SCIENTIFIC ACHIEVEMENT AND DELIVERY Brain development and function are orchestrally coordinated by numerous genetic factors, which are required to produce right amount of proteins in the right place at the right time. They are involved in fundamental cellular processes including neural proliferation, neuronal differentiationspecification, migration or brain cell communications. Increasing evidence suggest that most neurological conditions are associated with small effects of multiple genetic factors, via gain-of-function, loss-of-function or dys-regulation. Appropriate modeling of human genetic alterations in cells and animals are essential for understanding gene function in brain development and physiology, for validating genetic cause and observing neuropathogenesis, and for offering disease models to develop effective therapeutic treatment. I have generated and characterized 7 genetically modified mice, which are associated significant scientific discoveries.