Skip to main content
Cancer Training Grant Cancer Training Grant
  1. HOME
  2. Current Trainees
  3. Post Docs
  4. Ramya Raviram

Single Cell Epigenomic Analysis of Glioblastoma

Ramya Raviram
Appointment Period: 2016-2019, Grant Year: [31, 32]

Ramya Raviram

Glioblastoma (GBM) is the most common primary brain cancer of adults and one of the most lethal of all human malignancies. The epidermal growth factor receptor (EGFR) is amplified and/or mutated in up to 60% of GBMs, promoting tumor growth and survival through persistent activation of signaling networks and metabolic reprogramming. Our lab showed recently that EGFR activation resulted in altered epigenetic landscape in GBM, suggesting that global epigenetic analysis may provide new therapeutic insights. However, analysis of epigeneomic landscape can be confounded by heterogeneity of tumor samples. To overcome this challenge, I would like to develop single-cell based approaches for epigenomics analysis of GBM. Our lab has recently established a single nucleus ATAC-seq procedure suitable for frozen tissues. This strategy uses a combinatorial barcoding strategy that scales sublinearly and is thus highly cost-effective. As a proof of principle this strategy was applied to mouse forebrains and the major cell-types were digitally identified through clustering analysis of the snATACseq profiles of >2000 nuclei.

During my postdoctoral training, I will use snATAC-seq to investigate the chromatin landscapes at single cell resolution in GBM tumors. Dr. Clark Chen from UCSD Cancer Center has provided GBM tumor samples from five patients and will continue to provide samples for the proposed study. I plan to perform snATAC-seq experiments to identify the regions of open chromatin in individual cells in these biopsy samples. Subsequently, I will conduct computational analysis to identify sub-cell types in each tumor sample. In addition, I will also adopt single cell Hi-C analysis to profile chromatin organization in the tumors. I will then integrate snATAC-Seq and scHi-C with single cell RNA-Seq to gain insight into the epigenetic mechanism of GBM. I expect that results from the proposed study could lead to better diagnostic biomarkers for GBM and potentially novel therapeutic strategies. The research will provide me with opportunities to learn cutting edge genomic techniques and develop new computational methods.

PUBLICATIONS (resulting from this training)

Trainee recently appointed to grant, publications are still in progress.