Clinical Genomics and Computational Oncology to Study Metastatic Prostate Cancer
(Postdoctoral Research)
Celine's current research interests include: 1) the response and resistance to cancer therapies from genomic profiling of patient tumors, 2) innovative computational approaches for integrating genomic, epigenetic, transcriptomic and clinical data, and 3) tumor evolution and heterogeneity as etiologies of cancer therapy resistance, all ultimately towards the goal of identifying personalized treatment.
She obtained her Ph.D. degree in Bioinformatics and Genomics studying gene regulation and transcription factor binding in differentiation of blood stem cells to red blood cells at Penn State University using ChIP-exo, chromatin immunoprecipitation (ChIP) combined with exonuclease digestion followed by high-throughput sequencing.
Celine is an active member of Center for Cancer Precision Medicine (CCPM) at Dana-Farber, and Cancer Program of Broad Institute of MIT and Harvard. She is interested in bridging the gap between biologists and computer scientists through collaborative research, and also is involved in scientific education and outreach through teaching and mentoring.
She obtained her Ph.D. degree in Bioinformatics and Genomics studying gene regulation and transcription factor binding in differentiation of blood stem cells to red blood cells at Penn State University using ChIP-exo, chromatin immunoprecipitation (ChIP) combined with exonuclease digestion followed by high-throughput sequencing.
Celine is an active member of Center for Cancer Precision Medicine (CCPM) at Dana-Farber, and Cancer Program of Broad Institute of MIT and Harvard. She is interested in bridging the gap between biologists and computer scientists through collaborative research, and also is involved in scientific education and outreach through teaching and mentoring.
Transcriptional Regulation (Graduate Research)
Transcriptional regulation is important in many biological processes, where many transcription factors bind to the DNA and other protein for gene regulation, the control for which genes are turned on and off in the genome. Therefore, knowing the precise binding locations is important to understand the genes that are regulated.
Many Chromatin immunoprecipitation-based methods have been developed to study the binding location of the transcription factor of interest, such as ChIP-seq. However, the low resolution and sensitivity (signal:noise) of the assay limited their conclusions. Indeed the broad binding regions of ChIP-seq, which span over 100bp or even 1kb wide, makes it challenging to decipher the driving motif when numerous motifs are present within the region; it also did not allow us to distinguish the difference in binding pattern and distance between binding locations of co-occupied TFs.
ChIP-exo, which combines chromatin immunoprecipitation (ChIP) with lambda exonuclease digestion followed by high-throughput sequencing, has been developed in our lab to address these challenges. ChIP-exo allows the identification of the precise binding location with low background.
Many Chromatin immunoprecipitation-based methods have been developed to study the binding location of the transcription factor of interest, such as ChIP-seq. However, the low resolution and sensitivity (signal:noise) of the assay limited their conclusions. Indeed the broad binding regions of ChIP-seq, which span over 100bp or even 1kb wide, makes it challenging to decipher the driving motif when numerous motifs are present within the region; it also did not allow us to distinguish the difference in binding pattern and distance between binding locations of co-occupied TFs.
ChIP-exo, which combines chromatin immunoprecipitation (ChIP) with lambda exonuclease digestion followed by high-throughput sequencing, has been developed in our lab to address these challenges. ChIP-exo allows the identification of the precise binding location with low background.
Red Blood Cell Differentiation (Graduate Research)
Transcription factor binding is important even in hematopoiesis, the process that the hematopoietic stem cells (HSCs) undergo self-renewal and differentiation to various blood cell lineages. The differentiation to red blood cells, also referred as erythropoiesis, involves relatively small number of transcription factors (TFs), such as GATA1, SCL/TAL1, LMO2, LDB1, and others, which forms a multi-protein complex. Misregulation of these factors are known to be involved in Acute Myeloid Leukemia (AML).
Celine's work comprehensively mapped the binding locations of GATA1 and TAL1 at ultra-high-resolution using ChIP-exo in G1E (GATA1-/-) mouse erythroid cells at various times point after expression of an ectopic GATA1 (G1E, G1E-ER4 cells).
Celine's work comprehensively mapped the binding locations of GATA1 and TAL1 at ultra-high-resolution using ChIP-exo in G1E (GATA1-/-) mouse erythroid cells at various times point after expression of an ectopic GATA1 (G1E, G1E-ER4 cells).