A5028646004- Mitochondrial Function and Pathology
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Advanced Fluorescence Microscopy Techniques
- Photosynthetic Processes and Mechanisms
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- bioluminescence and chemiluminescence research
- Bioinformatics and Genomic Networks
- Chromatin Remodeling and Cancer
- CRISPR and Genetic Engineering
- Light effects on plants
- stochastic dynamics and bifurcation
- Circadian rhythm and melatonin
- Photoreceptor and optogenetics research
- RNA Interference and Gene Delivery
- Gene Regulatory Network Analysis
- Folate and B Vitamins Research
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
Massachusetts General Hospital
2020-2024
Howard Hughes Medical Institute
2020-2024
Broad Institute
2017-2023
Center for Systems Biology
2020-2023
Harvard University
2020-2023
University of California, San Francisco
2013-2017
Cardiovascular Institute Hospital
2015
Massachusetts Institute of Technology
2007-2010
IIT@MIT
2010
Transcriptional positive-feedback loops are widely associated with bistability, characterized by two stable expression states that allow cells to respond analog signals in a digital manner. Using synthetic system budding yeast, we show positive feedback involving promoter multiple transcription factor (TF) binding sites can induce steady-state bimodal response without cooperative of the TF. Deterministic models this do not predict bistability. Rather, requires short-lived TF and stochastic...
Abstract The SLC25 carrier family consists of 53 transporters that shuttle nutrients and co-factors across mitochondrial membranes. is highly redundant their transport activities coupled to metabolic state. Here, we use a pooled, dual CRISPR screening strategy knocks out pairs in four states — glucose, galactose, OXPHOS inhibition, absence pyruvate designed unmask the inter-dependence these genes. In total, screen 63 genes states, corresponding 2016 single pair-wise genetic perturbations. We...
Significance By harnessing the unique interactions between infrared fluorescent protein and its chromophore, we have designed an fluorogenic protease reporter (iProtease). A is ideal for imaging activity in vivo, whereas a FRET-based limited by poor signal requirement of image processing. The iProtease scaffold may be used as core module to design reporters various proteases with specific activity. This technology will aide important applications, including monitoring dissecting signaling...
There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence cultured cells and extends lifespan yeast, nematodes, fruit flies. Here, we asked whether chronic beneficial mammalian aging. We utilized Ercc1 Δ/- mouse model accelerated aging given these mice are born developmentally normal but exhibit anatomic, physiological, biochemical features across multiple organs. Importantly, they a shortened...
We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation their fibroblasts showed elevated oxygen consumption and decreased mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in ATP5F1B, which encodes β subunit ATP synthase (also called complex V). In yeast, mutations affecting same region loosen coupling between proton motive force synthesis, resulting high rates respiration....
A reversible green fluorogenic protein-fragment complementation assay was developed based on the crystal structure of UnaG, a recently discovered fluorescent protein. In living mammalian cells, nonfluorescent fragments complemented and rapidly became upon rapamycin-induced FKBP Frb protein interaction, lost fluorescence when interaction inhibited. This reporter, named uPPI [UnaG-based protein-protein (PPI) reporter], uses bilirubin (BR) as chromophore requires no exogenous cofactor. BR is an...
Abstract Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing metabolomics to identify candidate molecular effectors activated these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, unfolded protein response, lipid peroxide scavenging be increased in HCC. A CRISPR–Cas9 knockout screen a new HCC model reveals which pathways are...
Our current understanding of mitochondrial organelle physiology has benefited from two broad approaches: classically, cuvette-based measurements with suspensions isolated mitochondria, in which bioenergetic parameters are monitored acutely response to respiratory chain substrates and inhibitors
Oxygen plays a key role in supporting life on our planet. It is particularly important higher eukaryotes where it boosts bioenergetics as thermodynamically favorable terminal electron acceptor and has roles cell signaling development. Many human diseases stem from either insufficient or excessive oxygen. Despite its fundamental importance, we lack methods with which to manipulate the supply of oxygen high spatiotemporal resolution cells organisms. Here, introduce genetic system, SupplemeNtal...
Abstract The SLC25 carrier family consists of 53 transporters that shuttle nutrients and co-factors across mitochondrial membranes 1-3 . is highly redundant their transport activities coupled to metabolic state. Here, we introduce a pooled, dual CRISPR screening strategy knocks out pairs in four states — glucose, galactose, OXPHOS inhibition, absence pyruvate designed unmask the inter-dependence these genes. In total, screened 63 genes states, corresponding 2016 single pair-wise genetic...
The SARS-CoV-2 coronavirus has caused worldwide disruption through the COVID-19 pandemic, providing a sobering reminder of profound impact viruses can have on human well-being. Understanding virus life cycles and interactions with host cells lays groundwork for exploring therapeutic strategies against virus-related diseases. Fluorescence microscopy plays vital role in imaging, offering high spatiotemporal resolution, sensitivity, spectroscopic versatility. In this opinion piece, we first...
<p>Supplementary Figure 1: Mitochondrial and nuclear DNA alterations in an HCC cohort. Related to 1. Supplementary 2: Transcriptomic landscape of HCC. 2. 3: Metabolic signatures 3. 4: Authentic models 4. 5: CRISPR screen identifies vulnerability GPX4 loss 5. 6: NCI-HCC xenografts are sensitive ferroptosis. 6. 7: Differential effects OXPHOS inhibition on 7.</p>
<p>Supplementary Figure 1: Mitochondrial and nuclear DNA alterations in an HCC cohort. Related to 1. Supplementary 2: Transcriptomic landscape of HCC. 2. 3: Metabolic signatures 3. 4: Authentic models 4. 5: CRISPR screen identifies vulnerability GPX4 loss 5. 6: NCI-HCC xenografts are sensitive ferroptosis. 6. 7: Differential effects OXPHOS inhibition on 7.</p>
<p>Supplementary Table 1 describes the HCC clinical cohort</p>
<p>Supplementary Table 1 describes the HCC clinical cohort</p>