NIBR
POSTDOCTORAL PROGRAM

Bilaba BilicanBilada Bilican, PhD
Neuroscience
Cambridge, Massachusetts, United States


Research into mechanisms of neurological disorders have long been hampered by the relative lack of accessibility of human neuronal and glial cells of the nervous system. My group’s main focus is to overcome this limitation by developing human pluripotent stem cell (hPSC) models of neurological disorders. In particular, we are interested in using human neurons and glia to better understand the cell-autonomous and non-cell autonomous mechanisms of neurodegeneration. To this end, we develop novel differentiation protocols to generate disease-relevant cell types and use CRISPR/CAS9 genome engineering in human pluripotent stem cells to generate reporters to study disease-associated protein dynamics at physiological protein levels. Furthermore, we established a scalable automated differentiation platform to generate human cortical excitatory neurons from control, disease-associated, and engineered hPSCs for high-throughput disease phenotyping. We are leveraging these technologies along with close collaborations with computational biology, genomics, proteomics, and chemical biology screening teams to gain insights into disease biology, identify small molecules that modify cellular phenotypes, and explore new targets.

Our current aim is to develop two research areas further: (i) building regulatable protein aggregation models in human neurons using CRISPR/CAS9 genome engineering technology to study mechanisms of templated protein aggregation, spread, and toxicity, (ii) establishing a scalable methodology to generate human microglia to investigate contribution of microglia to psychiatric and neurodegenerative disorders. Ultimately, these two approaches will enable us to investigate molecular pathobiology of neurodegeneration in physiologically-relevant cellular models.

Selected Publications

Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models.
Barmada SJ, Serio A, Arjun A, Bilican B, Daub A, Ando DM, Tsvetkov A, Pleiss M, Li X, Peisach D, Shaw C, Chandran S, Finkbeiner S.
Nat Chem Biol. 2014 Aug;10(8):677-85.

Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy.
Serio A, Bilican B, Barmada SJ, Ando DM, Zhao C, Siller R, Burr K, Haghi G, Story D, Nishimura AL, Carrasco MA, Phatnani HP, Shum C, Wilmut I, Maniatis T, Shaw CE, Finkbeiner S, Chandran S.
Proc Natl Acad Sci USA. 2013 Mar 19;110(12):4697-702.

Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability.
Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S.
Proc Natl Acad Sci USA. 2012 Apr 10;109(15):5803-8.

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