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Bushra Raj, Ph.D.
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Assistant Professor of Cell and Developmental Biology
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Department: Cell and Developmental Biology
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Biomedical Research Building II/III
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31 421 Curie Blvd
Philadelphia, PA 19104
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13 Office 1109
31 421 Curie Blvd
Philadelphia, PA 19104
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Office: 215-898-4466
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Education:
21 a B.Sc. 1f (Molecular Genetics) c
36 University of Toronto, Canada, 2008.
21 a Ph.D. 1f (Molecular Genetics) c
36 University of Toronto, Canada, 2015.
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Permanent link21 a B.Sc. 1f (Molecular Genetics) c
36 University of Toronto, Canada, 2008.
21 a Ph.D. 1f (Molecular Genetics) c
36 University of Toronto, Canada, 2015.
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3f Gene regulatory code and dynamics of neural development
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10 Keywords
a3 neurogenesis, single-cell genomics, transcriptomics, brain development, cell specification, CRISPR/Cas, bioinformatics, lineage tracing, imaging, chromatin
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18 Research Details
4a3 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 insights into neurogenesis.
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Description of Research Expertise
23 Research Interests3f Gene regulatory code and dynamics of neural development
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10 Keywords
a3 neurogenesis, single-cell genomics, transcriptomics, brain development, cell specification, CRISPR/Cas, bioinformatics, lineage tracing, imaging, chromatin
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18 Research Details
4a3 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 insights into neurogenesis.
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106 Siniscalco AM, Perera RP, Greenslade JE, Veeravenkatasubramanian H, Masters A, Doll HM, Raj B.: Barcoding Notch signaling in the developing brain. Development 151: dev203102, December 2024.
8b Raj B.: Tracing developmental lineages. Nat Methods December 2023.
c3 Raj, B., Farrell, J.A., McKenna, A., Leslie, J.L., Schier, A.F.: Emergence of neuronal diversity during vertebrate brain development. Neuron 36 108(6): 1058-1074, December 2020.
11f 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.
1c2 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.
135 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.
ec 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 4c vertebrates. Science 349(6250): 868-73, August 2015.
f0 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.
f6 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., b7 Geschwind, D., Blencowe, B.J.: A highly conserved program of neuronal microexons is misregulated in autistic brain. Cell 159(7): 1511-23, December 2014.
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Selected Publications
b9 Raj B.: Single-Cell Profiling of Lineages and Cell Types in the Vertebrate Brain. Methods Mol Biol January 2025.106 Siniscalco AM, Perera RP, Greenslade JE, Veeravenkatasubramanian H, Masters A, Doll HM, Raj B.: Barcoding Notch signaling in the developing brain. Development 151: dev203102, December 2024.
8b Raj B.: Tracing developmental lineages. Nat Methods December 2023.
c3 Raj, B., Farrell, J.A., McKenna, A., Leslie, J.L., Schier, A.F.: Emergence of neuronal diversity during vertebrate brain development. Neuron 36 108(6): 1058-1074, December 2020.
11f 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.
1c2 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.
135 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.
ec 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 4c vertebrates. Science 349(6250): 868-73, August 2015.
f0 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.
f6 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., b7 Geschwind, D., Blencowe, B.J.: A highly conserved program of neuronal microexons is misregulated in autistic brain. Cell 159(7): 1511-23, December 2014.
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