Faculty

Bushra Raj, Ph.D.

Assistant Professor of Cell and Developmental Biology

Department: Cell and Developmental Biology

Graduate Group Affiliations

Contact information

Biomedical Research Building II/III
Office 1109
421 Curie Blvd
Philadelphia, PA 19104

Office: 215-898-4466

Email:
bushra.raj@pennmedicine.upenn.edu

Education:
B.Sc. (Molecular Genetics)
University of Toronto, Canada, 2008.
Ph.D. (Molecular Genetics)
University of Toronto, Canada, 2015.

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Description of Research Expertise

Research Interests
Gene regulatory code and dynamics of neural development

Keywords
neurogenesis, single-cell genomics, transcriptomics, brain development, cell specification, CRISPR/Cas, bioinformatics, lineage tracing, imaging

Research Details
Neurogenesis in the brain comprises many steps from proliferation of progenitors to differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. My lab is investigating transcriptional changes and genetic programs that contribute to the origins and fate of diverse neural cell types during zebrafish brain development. We are leveraging single-cell genomics, fate mapping and imaging approaches to characterize how neural progenitors undergo shifts in cell states across early and late stages of development at the transcript and chromatin levels. Additionally, we are coupling these datasets with Cas9-induced somatic mutations to ask how these changes impact progenitor identity, heterogeneity and lineage competency during early stages of brain organogenesis. Furthermore, we are investigating the molecular trajectories that underlie cell specification and differentiation and testing candidate regulators using knockout strategies. Collectively, our approach is expected to yield global and local views of neurogenesis.

Selected Publications

Raj, B., Farrell, J.A., McKenna, A., Leslie, J.L., Schier, A.F.: Emergence of neuronal diversity during vertebrate brain development. Neuron 108(6): 1058-1074, December 2020.

Gonatopoulos-Pournatzis, T., Wu, M., Braunschweig, U., Roth, J., Han, H., Best, A.J., Raj, B., Aregger, M., O'Hanlon, D., Ellis, J.D., Calarco, J.A., Moffat, J., Gingras, A.C., Blencowe, B.J.: Genome-wide CRISPR-Cas9 Interrogation of Splicing Networks Reveals a Mechanism for Recognition of Autism-Misregulated Neuronal Microexons. Molecular Cell 72(3): 510-524, November 2018.

Raj, B., Gagnon, J.A., Schier, A.F.: Large-scale reconstruction of cell lineages using single-cell readout of transcriptomes and CRISPR-Cas9 barcodes by scGESTALT. Nature Protocols 13(11): 2685-2713, November 2018.

Raj, B., Wagner, D.E., McKenna, A., Pandey, S., Klein, A.M., Shendure, J., Gagnon, J.A., Schier, A.F.: Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain. Nature Biotechnology 36(5): 442-50, June 2018.

Gueroussov, S., Gonatopoulos-Pournatzis, T., Irimia, M., Raj, B., Yuan-Lin, Z., Gingras, A.-C., Blencowe, B.J. : An alternative splicing event amplifies evolutionary differences between vertebrates. Science 349(6250): 868-73, August 2015.

Raj, B. and Blencowe, B.J.: Alternative splicing in the mammalian nervous system: recent insights into mechanisms and functional roles. Neuron 87(1): 14-27, July 2015.

Irimia, M., Weatheritt, R.J., Ellis, J., Parikshak, N.N., Gonatopoulos-Pournatzis, T., Babor, M., Quesnel-Vallières, M., Tapial, J., Raj, B., O’Hanlon, D., Barrios-Rodiles, M., Wrana, J.L., Roth, F., Geschwind, D., Blencowe, B.J.: A highly conserved program of neuronal microexons is misregulated in autistic brain. Cell 159(7): 1511-23, December 2014.

Raj, B., Irimia, M., Braunschweig, U., Sterne-Weiler, T., O’Hanlon, D., Yuan-Lin, Z., Chen, G.I., Easton, L., Ule, J., Gingras, A.-C., Eyras, E. and Blencowe, B.J.: Global regulatory mechanism underlying the activation of an exon network required for neurogenesis. Molecular Cell 56(1): 90-103, October 2014.

Raj, B., O’Hanlon, D., Vessey, J.P., Pan, Q., Ray, D., Buckley, N.J., Miller, F.D., and Blencowe, B.J.: Cross-regulation between an alternative splicing regulator and a transcription repressor controls neurogenesis. Molecular Cell 43(5): 843-50, September 2011.

Calarco, J.A., Superina, S., O’Hanlon, D., Gabut, M., Raj, B., Pan, Q., Skalska, U., Clarke, L., Gelinas, D., van der Kooy, D., Zhen, M., Ciruna, B., and Blencowe, B.J.: Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell 138(5): 898-910, September 2009.