Primary AppointmentBiochemistry and Molecular Genetics
Contact InformationEmail: firstname.lastname@example.org
Regulation of stem cell function and tumorigenicity by epigenetic and novel biophysical mechanisms
The broad interest of the Jiang lab is how gene regulation at the chromatin, transcriptional, and post-transcriptional levels controls the stability and plasticity of cell identity, how dysregulation of these mechanisms lead to diseases especially cancer, and how we may develop novel molecules to combat these diseases based on these mechanisms. We are studying the functional role of efficient H3K4 methylation in regulating stem cell fate determination and tumorigenesis. We have shown that Dpy30, one of the core subunits in the Set1/Mll family of H3K4 methyltransferases, plays an important role in the fate determination of embryonic (Jiang et al, Cell 2011) and hematopoietic (Yang et al., Blood 2014; Yang et al., J Exp Med 2016) stem cells. Moreover, our recent studies using our genetically engineered mouse model strongly suggest that cancer cells hijack this epigenetic modulator to drive a gene expression program supporting tumorigenesis, meanwhile creating ?epigenetic vulnerability?. We are currently studying the molecular mechanisms underlying such epigenetic vulnerability and also developing pharmacologic intervention strategies to target this modulator for potential cancer treatment. It remains largely unclear how gene expression is spatiotemporally regulated in cells and how such spatiotemporal control of gene expression impacts physiological and pathological processes. AKAP95 is associated with several human diseases including cancer, but the molecular activities of AKAP95 are poorly defined. Our previous work (Jiang et al., Nat Struct Mol Biol 2013) has identified AKAP95 as a remarkable transcription co-activator. We have recently shown that, surprisingly, AKAP95 is an RNA-binding protein and regulates alternative pre-mRNA splicing by direct interaction with pre-mRNA and hnRNP proteins (Hu et al., Nat Comm 2016). We have recently started to study a novel biophysical mechanism by which AKAP95 and related factors spatiotemporally regulate transcription and splicing to control animal development and diseases. Currently, our research is funded by the NIH, American Society of Hematology, American Cancer Society, and Leukemia & Lymphoma Society.