Name: PINS: "Integrative Modeling of Human Brain Development and Neurodevelopment Disorders"
Start: 2021-04-01T16:00:00-04:00
End: 2021-04-01T17:00:00-04:00

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Bennett Novitch, Ph.D.

Professor and Ethel Scheibel Chair in Neuroscience

Department of Neurobiology

Broad Stem Cell Research Center

David Geffen School of Medicine at UCLA

Abstract:

The remarkable information processing capacity of the human brain is thought to derive from its enormous mass, cellular density, and structural complexity. Defects in brain growth and organization result in a host of neurodevelopmental disorders, neuropsychiatric diseases, and intellectual disabilities. A key step towards understanding the normal and abnormal functions of the brain thus lies in defining the mechanisms that control brain growth and neural circuit activities. Experimentally studying human brain development is inherently challenging. However, recent studies have demonstrated that some aspects of brain growth can be modeled through the directed differentiation of human pluripotent stem cells into 3-dimensional structures commonly referred to as organoids. While significant progress has been made, many challenges remain including consistency and reproducibility in organoid production and formal demonstrations of the extent to which brain organoids accurately recapitulate human development and disease in vivo. In my presentation, I will describe our work developing reliable organoid platforms, illustrate the similarities the developing human brain in vivo, and discuss our ongoing efforts to model neurodevelopmental disorders such as microcephaly, autism spectrum disorders, and epilepsy.

References Cited:

Watanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh B, Coppola G, Pearson CA, Yamauchi K, Gong D, Dai X, Damoiseaux R, Aliyari R, Liebscher S, Schenke-Layland K, Caneda C, Huang EJ, Zhang Y, Cheng G, Geschwind DH, Golshani P, Sun R, Novitch BG. Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection. Cell Rep. 2017; 21(2):517-532. https://doi.org/10.1016/j.celrep.2017.09.047.

Samarasinghe RA, Miranda OA, Buth JE, Mitchell S, Ferando I, Watanabe M, Allison TF, Kurdian A, Fotion NN, Gandal MJ, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. Identification of neural oscillations and epileptiform changes in human brain organoids. bioRxiv. 2021,820183. https://doi.org/10.1101/820183.

Watanabe M, Haney JR, Vishlaghi N, Turcios F, Buth JE, Gu W, Collier AJ, Miranda OA, Chen D, Sabri S, Clark AT, Plath K, Christofk HR, Gandal MJ, Novitch BG. TGFβ superfamily signaling regulates the state of human stem cell pluripotency and competency to create telencephalic organoids. bioRxiv, 2019; 875773. https://doi.org/10.1101/2019.12.13.875773.

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