The Candidate proposes a five-year career development and research program under the mentorship of Prof. Andrea Califano. The Candidate's career goal is to build an independent research program at Columbia University focusing on engineering new tools for system-wide interrogation of single cells with direct applications in biomedicine. The research component involves the development of a microfluidic array platform that allows highly parallel optical imaging and RNA capture from single cells. Importantly, the array elements are individually addressable so that RNA libraries from individual cells-of-interest can be extracted for RNA-Seq. This system will allow the Candidate and his collaborators to address key questions about tumor composition and progression in glioblastoma, a common and unusually heterogeneous type of brain tumor. Although the Candidate has a strong technology-oriented background, he requires significant training in order to carry out the biomedical aspects of the proposal. Hence, the career development component focuses on acquiring skills related to 1) tissue handling, dispersing single cell suspensions from tissue, and culturing tissue-derived cells; 2) labeling, FACS, and laser capture of tissue-derived cells; and 3) RNA stabilization/extraction and bioinformatics. In addition, the career development plan includes specific coursework in these areas as well as mentoring in grant-writing and scientific communication and hypothesis development in biomedical research. Columbia has well-established research programs in these areas and substantial shared resources which will be leveraged in various parts of the proposal. This award will facilitate the candidate's transitio as an independent biomedical researcher and the formation of valuable collaborations.
Cellular heterogeneity poses a serious challenge to conventional bulk studies of glioblastoma, a common form of brain tumor that is particularly difficult to treat. By enabling quantification of transcriptomes from the exact individual cells phenotypically characterized in an imaging experiment, this project will significantly enhance our ability to understand these complex systems, analyze clinical samples, and ultimately design more effective treatments.
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|Bush, Erin C; Ray, Forest; Alvarez, Mariano J et al. (2017) PLATE-Seq for genome-wide regulatory network analysis of high-throughput screens. Nat Commun 8:105|
|Yuan, Jinzhou; Sims, Peter A (2016) An Automated Microwell Platform for Large-Scale Single Cell RNA-Seq. Sci Rep 6:33883|
|Hornstein, Nicholas; Torres, Daniela; Das Sharma, Sohani et al. (2016) Ligation-free ribosome profiling of cell type-specific translation in the brain. Genome Biol 17:149|
|Sims, Jennifer S; Grinshpun, Boris; Feng, Yaping et al. (2016) Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire. Proc Natl Acad Sci U S A 113:E3529-37|
|Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K et al. (2016) Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma. Mol Cancer Ther 15:1332-43|
|Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K et al. (2016) Quantitative phosphoproteomics reveals Wee1 kinase as a therapeutic target in a model of proneural glioblastoma. Mol Cancer Ther :|
|Bose, Sayantan; Wan, Zhenmao; Carr, Ambrose et al. (2015) Scalable microfluidics for single-cell RNA printing and sequencing. Genome Biol 16:120|
|Venere, Monica; Horbinski, Craig; Crish, James F et al. (2015) The mitotic kinesin KIF11 is a driver of invasion, proliferation, and self-renewal in glioblastoma. Sci Transl Med 7:304ra143|
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