A5088787388- Advanced NMR Techniques and Applications
- Advanced MRI Techniques and Applications
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Electron Spin Resonance Studies
- Amino Acid Enzymes and Metabolism
- Medical Imaging Techniques and Applications
- Mitochondrial Function and Pathology
- Atomic and Subatomic Physics Research
- Angiogenesis and VEGF in Cancer
- Metabolomics and Mass Spectrometry Studies
- Multiple Sclerosis Research Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Solid-state spectroscopy and crystallography
- Cancer Cells and Metastasis
- Polyomavirus and related diseases
- Advanced Neuroimaging Techniques and Applications
- Adipose Tissue and Metabolism
- Functional Brain Connectivity Studies
- Enzyme Structure and Function
- Neuroinflammation and Neurodegeneration Mechanisms
- Barrier Structure and Function Studies
- Neuroscience and Neuropharmacology Research
- Cerebrovascular and genetic disorders
- Lanthanide and Transition Metal Complexes
University of California System
2015-2025
University of California, San Francisco
2016-2025
American Physical Therapy Association
2017-2025
Bioengineering Center
2025
University of California, Berkeley
2019-2025
Laboratoire d’Imagerie Biomédicale
2014
Universidad Católica de Santa Fe
2014
Neurological Surgery
2010-2013
Centre National de la Recherche Scientifique
2006-2013
UCSF Helen Diller Family Comprehensive Cancer Center
2013
Neurons require large amounts of energy, but whether they can perform glycolysis or to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through and rely on supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, generated mice with postnatal deletion either dominant neuronal transporter (GLUT3cKO) neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 other hippocampal neurons. GLUT3cKO PKM1cKO...
Abstract Purpose: To identify mediators of glioblastoma antiangiogenic therapy resistance and target these in xenografts. Experimental Design: We conducted microarray analysis comparing bevacizumab-resistant glioblastomas (BRG) with pretreatment tumors from the same patients. established novel xenograft models to candidate mediator(s). Results: BRG revealed upregulation versus receptor tyrosine kinase c-Met, which underwent further investigation because its prior biologic plausibility as a...
Mutations of the isocitrate dehydrogenase 1 and 2 gene (IDH1/2) were initially thought to enhance cancer cell survival proliferation by promoting Warburg effect. However, recent experimental data have shown that production 2-hydroxyglutarate IDH mutant cells promotes hypoxia-inducible factor (HIF)1α degradation and, doing so, may unexpected metabolic effects. We used human glioma tissues derived brain tumor stem (BTSCs) study expression HIF1α target genes in (mt) wild-type (wt) tumors....
Abstract Numerous mechanism-based anticancer drugs that target the phosphatidylinositol 3-kinase (PI3K) pathway are in clinical trials. However, it remains challenging to assess responses by traditional imaging methods. Here, we show for first time efficacy of hyperpolarized 13C magnetic resonance spectroscopy (MRS) detecting effect PI3K inhibition monitoring [1-13C]lactate levels produced from [1-13C]pyruvate through lactate dehydrogenase (LDH) activity. In GS-2 glioblastoma cells, LY294002...
Traumatic brain injury (TBI) is of particular concern for the aging community since there both increased incidence TBI and decreased functional recovery in this population. In addition, strongest environmental risk factor development Alzheimer’s disease other dementia-related neurodegenerative disorders. Critical changes that affect cognition take place over time following initial insult. Our previous work identified immune system activation as a key contributor to cognitive deficits...
Mutant isocitrate dehydrogenase 1 (IDH1) catalyzes the production of 2-hydroxyglutarate but also elicits additional metabolic changes. Levels both glutamate and pyruvate (PDH) activity have been shown to be affected in U87 glioblastoma cells or normal human astrocyte (NHA) expressing mutant IDH1, as compared with wild-type IDH1. In this study, we show how these phenomena are linked through effects IDH1 mutation, which reprograms metabolism. Reduced PDH NHA was associated relative increases...
The phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is activated in more than88% glioblastomas (GBM). New drugs targeting this are currently clinical trials. However, noninvasive assessment treatment response remains challenging. By using magnetic resonance spectroscopy (MRS), PI3K/Akt/mTOR inhibition was monitored 3 GBM cell lines (GS-2, GBM8, and GBM6; each with a distinct activating mutation) through the measurement 2 mechanistically...
Abstract Mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among most prevalent in low-grade glioma and secondary glioblastoma, represent an early pathogenic event, associated with epigenetically driven modulations metabolism. Of particular interest is recently uncovered relationship between IDH1 mutation decreased activity branched-chain amino acid transaminase (BCAT1) enzyme. Noninvasive imaging methods that can assess BCAT1 could therefore improve detection mutant tumors aid...
Significance Cells from the innate immune system, namely microglia and macrophages (mononuclear phagocytes, MPs), play a central role in progression of neurological disorders such as multiple sclerosis. Such cells can contribute to lesion formations (proinflammatory) or participate remyelinating processes (neuroprotective). When differentiated proinflammatory phenotype, MPs experience metabolic reprogramming leading increased glycolysis production lactate. In this study we showed that new...
Background Mutations in isocitrate dehydrogenase (IDH) 1 have been reported over 70% of low-grade gliomas and secondary glioblastomas. IDH1 is the enzyme that catalyzes oxidative decarboxylation to α-ketoglutarate while mutant conversion into 2-hydroxyglutarate. These mutations are associated with accumulation 2-hydroxyglutarate within tumor believed be one earliest events development gliomas. The goal this work was determine whether mutation leads additional magnetic resonance spectroscopy...
Over 70% of low-grade gliomas carry a heterozygous R132H mutation in the gene coding for isocitrate dehydrogenase 1 (IDH1). This confers enzyme with novel ability to convert α-ketoglutarate 2-hydroxyglutarate, ultimately leading tumorigenesis. The major source 2-hydroxyglutarate production is glutamine, which, cancer, also tricarboxylic acid cycle (TCA) anaplerosis. An alternate anaplerosis pyruvate flux via carboxylase (PC), which common pathway normal astrocytes. goal this study was...
Recent findings show that exposure to temozolomide (TMZ), a DNA-damaging drug used treat glioblastoma (GBM), can suppress the conversion of pyruvate lactate. To understand mechanistic basis for this effect and its potential utility as TMZ response biomarker, we compared isogenic GBM cell populations differing only in expression DNA repair protein methyltransferase (MGMT), TMZ-sensitivity determinant, after vitro vivo. Hyperpolarized [1-((13))C]-pyruvate-based MRI was monitor temporal effects...
Metabolic imaging of brain tumors using 13C Magnetic Resonance Spectroscopy (MRS) hyperpolarized [1-13C] pyruvate is a promising neuroimaging strategy which, after decade preclinical success in glioblastoma (GBM) models, now entering clinical trials multiple centers. Typically, the presence GBM has been associated with elevated lactate produced from pyruvate, and response to therapy drop lactate. However, date, lower grade gliomas had not investigated this approach. The most prevalent...
Neurovascular coupling (NVC), a vital physiological process that rapidly and precisely directs localized blood flow to the most active regions of brain, is accomplished in part by vast network cerebral capillaries acting as sensory web capable detecting increases neuronal activity orchestrating dilation upstream parenchymal arterioles. Here, we report Col4a1 mutant mouse model small vessel disease (cSVD) with age-dependent defects capillary-to-arteriole dilation, functional hyperemia memory....
The positron emission tomography (PET) tracer 2-deoxy-2-[18F]fluoroglucose ([18F]FDG) is widely used to study diseases where glucose metabolism dysregulated, including cancer and neurodegenerative disorders. Here we investigate the hypothesis that 2-position deuterium-enriched analogue 2-deoxy-2-[2H2]-d-glucose (2-DG-d2) can also map uptake using deuterium metabolic imaging (DMI) without ionizing radiation. To accomplish this, a spectrally selective multiband radiofrequency pulse balanced...
Traumatic brain injury (TBI) has long been identified as a precipitating risk factor for higher-order cognitive deficits associated with the frontal and prefrontal cortices (PFC). In addition, mild repetitive TBI (rTBI), in particular, is being steadily recognized to increase of neurodegenerative disease. Thus, further understanding how rTBI changes pathophysiology lead impairment warranted. The current models lack knowledge regarding chronic functions underlying neuronal physiology,...
Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of impairments associated with TBI pathogenesis. We investigated whether 13C MRSI hyperpolarized (HP) [1-13C] pyruvate, a non-invasive imaging method, could detect changes controlled cortical (CCI) mice (n = 57). Our results show that HP lactate-to-pyruvate ratios were increased the injured cortex at...
The current standard of care for glioblastoma (GBM) is surgical resection, radiotherapy, and treatment with temozolomide (TMZ). However, resistance to therapies recurrence are common. To improve survival, agents that target the PI3K signaling pathway, which activated in approximately 88% GBM, currently clinical trials. A challenge such tumor shrinkage not always observed. New imaging methods therefore needed monitor response therapy predict survival. goal this study was determine whether...
Traumatic brain injury (TBI) is a major public health problem. Despite considerable research deciphering pathophysiology, precision therapies remain elusive. Here, we present large-scale data sharing and machine intelligence approaches to leverage TBI complexity. The Open Data Commons for (ODC-TBI) community-centered repository emphasizing Findable, Accessible, Interoperable, Reusable publication with persistent identifiers. Importantly, the ODC-TBI implements of individual subject data,...