Integrative Epigenomics in Hematologic Malignancies

Rationale:

Aberrant transcriptional programming is a hallmark of cancer, and is dependent on the deregulated action of transcription factors and chromatin modifying proteins. The phenotype of a given tumor is dependent on the collective information contained within the DNA sequence and epigenetic settings associated with the genome. We hypothesize that integrative analysis of epigenetic and genetic settings in cancer cells can provide a rational basis for more accurately modeling the critical biological pathways involved in mediating the malignant phenotype of tumors in individual patients. We also predict that epigenomic integrative analysis can be used to determine the identity of chromatin and transcription factors that contribute mechanistically to aberrant transcriptional programming in given tumors, and that this information can be used for designing therapeutic strategies.

Goals:

To develop tools for integrative analysis of epigenomic and genetic characteristics of primary human cancer cells.
To determine the natural heterogeneity of human tumor types based on the distribution and patterning of their epigenetic and genetic characteristics
To identify the biochemical and biological basis of tumor phenotypes based on their epigenomic signatures
To design personalized targeted therapy approaches for treating patients with specific epigenetic signatures.


Projects:

Integrative epigenomics to improve the classification and therapeutic stratification of acute myeloid leukemias.
The contribution of epigenetic programming to the phenotype and response to epigenetic drug therapy in hematologic malignancies.
The contribution of epigenomic programming to disease progression and propensity to relapse in AML and myelodysplasia.
Integrative epigenomics to identify molecular pathways involved in lymphomagenesis.
Combining computational biology and biostatistics for the development of integrative epigenomics analysis methodologies.

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