A5055105366- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- Cholesterol and Lipid Metabolism
- RNA Research and Splicing
- Retinoids in leukemia and cellular processes
- SARS-CoV-2 and COVID-19 Research
- Estrogen and related hormone effects
- RNA Interference and Gene Delivery
- Peroxisome Proliferator-Activated Receptors
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Circular RNAs in diseases
- Sirtuins and Resveratrol in Medicine
- Computational Drug Discovery Methods
- Advanced biosensing and bioanalysis techniques
- Reproductive System and Pregnancy
- Cancer-related Molecular Pathways
- COVID-19 Clinical Research Studies
- Steroid Chemistry and Biochemistry
- Wnt/β-catenin signaling in development and cancer
- Lipid metabolism and biosynthesis
Massachusetts General Hospital
2012-2023
Harvard University
2012-2023
University of California, Berkeley
1998-2022
Innovative Genomics Institute
2021-2022
Center for Cancer Research
2016-2021
Harvard University Press
2004-2011
Molecular Oncology (United States)
2008
Institute of Cell Biology
2008
Howard Hughes Medical Institute
1991-2002
Lawrence Berkeley National Laboratory
2002
Proper coordination of cholesterol biosynthesis and trafficking is essential to human health. The sterol regulatory element-binding proteins (SREBPs) are key transcription regulators genes involved in uptake. We show here that microRNAs (miR-33a/b) embedded within introns the SREBP target adenosine triphosphate-binding cassette transporter A1 (ABCA1), an important regulator high-density lipoprotein (HDL) synthesis reverse transport, for posttranscriptional repression. Antisense inhibition...
Retinoic acid, thyroid hormone, and vitamin D receptors preferentially activate target genes through response elements that consist of direct repeat arrangements a core recognition motif consensus sequence AGGTCA. We present evidence the preference for arises from two fundamental differences steroid hormone receptors. First, retinoic are demonstrated to form heterodimers with retinoid X These interactions mediated by carboxy-terminal dimerization interface, heterodimer specified actions...
The sterol regulatory element-binding protein (SREBP) transcription factor family is a critical regulator of lipid and homeostasis in eukaryotes. In mammals, SREBPs are highly active the fed state to promote expression lipogenic cholesterogenic genes facilitate fat storage. During fasting, SREBP-dependent lipid/cholesterol synthesis rapidly diminished mouse liver; however, mechanism has remained incompletely understood. Moreover, evolutionary conservation fasting regulation programs gene...
Abstract Circulating tumor cells (CTC) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from patients with melanoma coordinately upregulate lipogenesis and iron homeostasis pathways. These correlated both intrinsic acquired resistance BRAF inhibitors across clonal cultures of BRAF-mutant CTCs. The regulator SREBP2 directly induces transcription carrier Transferrin (TF), reducing intracellular pools,...
SARS-CoV-2 is a betacoronavirus with single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Although population average structure models of were recently reported, there little experimental data on native structural ensembles, and most structures lack functional characterization. Here we report secondary heterogeneity entire in two lines infected cells at single nucleotide resolution. Our results reveal alternative conformations across critical...
The human cofactor complexes ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1 activation) mediate activator-dependent transcription in vitro. Although these share several common subunits, their structural functional relationships remain unknown. Here, we report that affinity-purified consists of two distinct multisubunit complexes: a larger complex, denoted ARC-L, smaller coactivator, CRSP. Reconstituted vitro with biochemically separated ARC-L reveals differential...
The promoter selectivity factor Sp1 often cooperates with other enhancer-binding proteins to activate transcription. To study the molecular underpinnings of these regulatory events, we have reconstituted in vitro synergy observed vivo between and sterol-regulated SREBP-1a at low density lipoprotein receptor ( LDLR ) promoter. Using a highly purified human transcription system, found that chromatin, TAFs, novel SREBP-binding coactivator activity, which includes CBP, are all required mediate...