Lab Location: CMM-West, Rm. 345
Lab Phone: 858-534-5858
Lab Composition and Activities: Five graduate students from several programs, and a talented group of enthusiastic (also helpful) postdoctoral fellows and a full time laboratory manager. We have one general laboratory meeting, one graduate student-only meeting, and one personal meeting each week. We also have joint lab meetings with two other labs weekly.
Research Interests: Our central laboratory focus this year is to continue to utilize global genomic approaches to uncover and investigate the “enhancer code” controlled by new, previously unappreciated pathways that integrate the genome-wide response to permit proper development and homeostasis, and that also functions in disease and senescence. We have investigated these events in differentiated cells, neuronal development, stem cells, and cancer. Our biological focus is on molecular mechanisms of the “enhancer code” regulating learning and memory; aggressive prostate and breast cancer, and they underlying events of senescence/aging. Epigenomic events studied include non-histone methylation events and non-coding RNAs. We are investigating these events in development, breast and prostate cancers, and in inflammation-based disease, including degenerative CNS disease and diabetes. The emerging importance of non-coding RNAs and regulation of nuclear architecture is rapidly altering our concepts of homeostasis and disease. Our laboratory is “Seq-ing” (RIP-seq, ChIP-seq, RNA-seq, GRO-seq, CLIP-seq, ChIRP-seq), and a new “FISH-seq”, for open-ended discovery of long-distance genome interactions to uncover new “rules” of regulated gene transcriptional programs and new roles for lncRNAs in biology of normal, cancer neuro-affective disorders and aging cells. Coupling this with chemical library screens, we hope to introduce new types of therapies based on targeting specific gene enhancers, histone protein readers and writers, and lncRNAs for cancers and other diseases. Recent surprising findings have been novel roles of lncRNAs prostate and breast cancer, connection between DNA damage repair/transcription and replication, and unexpected roles of enhancer RNAs.
Current interests include:
- The “enhancer code,” Epigenomics and transcriptional regulatory mechanisms.
- Roles of by ncRNAs in enhancer function in signal-dependent genomic relocation and in establishing subnuclear architecture.
- Mechanisms of signal-induced tumor chromosomal translocations events and new chemical screens for inhibitors for breast and prostate cancer.
- The “enhancer code” or regulation of learning and memory, including Reelin-regulated enhancers.
- Linkage of DNA damage/repair and transcription.
- Retinoic Acid regulation of Pol III-transcribed DNA repeats in maintenance of the stem cell state, in neuronal differentiation and in senescence.
- Molecular mechanisms of prevelant disease associated sequence variations (GWAS) in disease susceptibility loci.
- “Epigenomics” in neuronal differentiation, cancer, diabetes and degenerative brain disease.
- Answering the question when and how enhancers arise and became functional (stem cells to mature cell types).