A5056463824- Neuroscience and Neuropharmacology Research
- Glioma Diagnosis and Treatment
- Alzheimer's disease research and treatments
- Sleep and Wakefulness Research
- Photoreceptor and optogenetics research
- Radiomics and Machine Learning in Medical Imaging
- Receptor Mechanisms and Signaling
- Radiopharmaceutical Chemistry and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Circadian rhythm and melatonin
- Medicinal Plants and Neuroprotection
- Cancer Immunotherapy and Biomarkers
- Hepatocellular Carcinoma Treatment and Prognosis
- Neural dynamics and brain function
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Science, Research, and Medicine
- Immunotherapy and Immune Responses
- Neuroendocrine regulation and behavior
- Sex and Gender in Healthcare
- Mitochondrial Function and Pathology
- Phytochemistry and Biological Activities
- Stress Responses and Cortisol
- CNS Lymphoma Diagnosis and Treatment
- Trace Elements in Health
Dana-Farber Cancer Institute
2023-2024
Center for Neuro-Oncology
2024
Boston University
2023
MaineGeneral Medical Center
2020-2023
Harvard University
2020-2023
Massachusetts General Hospital
2020-2023
Boston College
2020
Abstract Mitochondria contribute to shape intraneuronal Ca 2+ signals. Excessive taken up by mitochondria could lead cell death. Amyloid beta (Aβ) causes cytosolic overload, but the effects of Aβ on mitochondrial levels in Alzheimer’s disease (AD) remain unclear. Using a ratiometric indicator targeted neuronal and intravital multiphoton microscopy, we find increased associated with plaque deposition death transgenic mouse model cerebral β-amyloidosis. Naturally secreted soluble applied onto...
Abstract Alzheimer’s disease (AD) is characterized by progressive memory loss and cognitive decline. These impairments correlate with early alterations in neuronal network activity AD patients. Disruptions the of individual neurons have been reported mouse models amyloidosis. However, impact amyloid pathology on spontaneous distinct types remains unexplored vivo. Here we use vivo calcium imaging multiphoton microscopy to monitor compare excitatory two inhibitory interneurons cortices APP/PS1...
Abstract Background Alzheimer’s disease (AD) patients exhibit memory disruptions and profound sleep disturbances, including disruption of deep non-rapid eye movement (NREM) sleep. Slow-wave activity (SWA) is a major restorative feature NREM important for consolidation. Methods We generated mouse model where GABAergic interneurons could be targeted in the presence APPswe/PS1dE9 (APP) amyloidosis, APP-GAD-Cre mice. An electroencephalography (EEG) / electromyography (EMG) telemetry system was...
Fear is adaptive when the level of response rapidly scales to degree threat. Using a discrimination procedure consisting danger, uncertainty, and safety cues, we have found rapid fear scaling (within 2 s cue presentation) in male rats. Here, examined possible role for nucleus accumbens core (NAcc) acquisition expression scaling. In experiment 1, Long–Evans rats received bilateral sham or neurotoxic NAcc lesions, recovered, underwent discrimination. NAcc-lesioned were generally impaired...
The key pathologic entities driving the destruction of synaptic function and integrity during evolution Alzheimer's disease (AD) remain elusive. Astrocytes are structurally functionally integrated within vascular circuitry use calcium-based physiology to modulate basal transmission, dynamics, neurovascular coupling, which central AD pathogenesis. We used high-resolution multiphoton imaging quantify all endogenous calcium signaling arising spontaneously throughout astrocytic somata, primary...
Patients with Alzheimer's disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute activity, we used multiphoton microscopy optogenetics investigate whether they APP/PS1 mice. The power but not frequency astrocytic calcium...
2016 Background: Ibudilast is a selective inhibitor of macrophage inhibitory factor (MIF) activity, which upregulated in GBM and promotes stem cell growth. It also disrupts the interaction between MIF CD74. When combined with temozolomide (TMZ) preclinical studies, it attenuates immunosuppressive properties myeloid-derived suppressor cells enhances tumor regression. This phase 1b/2a single-center, open-label, dose escalation study evaluating safety, tolerability, efficacy combination TMZ...
Abstract Alzheimer’s disease (AD) is characterized by synaptic loss and neuronal network dysfunction. These deficits are mediated early alterations in firing rates that coincide with amyloid plaque accumulation. Mounting evidence supports inhibitory networks impaired AD, but the mechanisms driving these poorly understood. Here we use vivo multiphoton calcium imaging to determine relationship between accumulation spontaneous activity of excitatory neurons interneurons an APP/PS1 mouse model...
Abstract Alzheimer’s disease (AD) is an incurable neurodegenerative disorder and a major cause of dementia. Some the hallmarks AD include presence amyloid plaques in brain parenchyma, calcium dysregulation within individual neurons, neuroinflammation. A promising therapeutic would reverse or stymie these pathophysiologies animal model AD. We tested effect NB-02, previously known as DA-9803, novel multimodal therapeutic, on deposition, neuronal regulation neuroinflammation 8- to 10-month-old...
Abstract Patients with Alzheimer’s disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute activity, we used multiphoton microscopy optogenetics investigate whether they APP mice. The power but not frequency astrocytic calcium...
Abstract Fear is adaptive when the level of response rapidly scales to degree threat. Using a discrimination procedure consisting danger, uncertainty and safety cues, we have found rapid fear scaling (within two seconds cue presentation) in male rats. Here examined possible role for nucleus accumbens core (NAcc) acquisition expression scaling. In experiment 1, Long Evans rats received bilateral sham or neurotoxic NAcc lesions, recovered underwent discrimination. NAcc-lesioned were generally...
Abstract Glioblastoma is immunologically “cold” and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature response ICI suggested that may improve survival. To increase the power this observation, we performed bulk-RNA seq on resected tumor tissue from an additional 25 patients with treated pembrolizumab. Neoadjuvant was associated suppression cell...
Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature response ICI suggested that may improve survival. To increase the power this observation, we enrolled an additional 25 patients with primary endpoint evaluating cell cycle gene associated performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant...
2056 Background: Somatic mutations in isocitrate dehydrogenase 1 (IDH) are recognized as an important prognostic factor patients with gliomas and associated longer survival. Regardless of initial grade, however, recurrence transformation into higher grade tumors is almost universal. IDH-mutant prone to develop hypermutation after exposure alkylating agents; other solid tumors, may be a predictive biomarker for PD-1 inhibitor response. In this multicenter phase 2, open label, single arm...
Abstract BACKGROUND Astrocytoma, IDH-mutant, WHO grade 4, are classified as a separate entity in the 2021 classification of central nervous system tumors and have been poorly characterized literature. In this study, we report on clinical outcomes large cohort newly diagnosed 4 IDH-mutant astrocytoma. METHODS We retrospectively identified adult patients with astrocytoma, treated for their initial diagnosis at Dana-Farber Cancer Institute Massachusetts General Hospital between 2010 2021....
Abstract BACKGROUND Somatic mutations in isocitrate dehydrogenase 1 (IDH1) are an important prognostic factor patients with gliomas. IDH-mutant gliomas prone to develop hypermutation after exposure alkylating agents; other solid tumors, may be a predictive biomarker for PD-1 inhibitor response. In this study, we hypothesize that specific subgroup of would clinically benefit from nivolumab as measured by overall response rate (ORR), duration (DOR), median progression-free survival (PFS), and...
Abstract BACKGROUND QBS10072S, is a L-type amino acid transporter 1 (LAT-1) targeted alkylating agent that utilizes LAT1 as both transport and targeting mechanism. QBS10072S can cross the blood-brain barrier, exhibits potential for cytotoxicity with mechanism distinct from temozolomide has low off-target effects. being evaluated in Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial (NCT02977780), randomized phase 2 adaptive multi-arm platform trial. METHODS...
Patients with Alzheimer’s disease (AD) exhibit sleep disturbances, specifically deficits in deep non-rapid eye movement (NREM) sleep. Disruption of NREM slow waves occurs early the progression and is recapitulated transgenic mouse models beta-amyloidosis. However, mechanisms underlying slow-wave disruptions remain unknown. Also, it not clear if these disturbances are a cause or effect AD. Because astrocytes contribute to activity, we used multiphoton microscopy optogenetics investigate...
Abstract BACKGROUND PCNSL exhibit B-cell receptor (BCR) pathway activation due to CD79B and MYD88 mutations, concurrently with 9p24.1/PD-L1/PD-L2 copy number alterations. These genetic features suggest complementary approaches of targeting PD1, BCR/BTK (Bruton’s tyrosine kinase) CD20. Pembrolizumab, ibrutinib rituximab have each been used as monotherapy in RR PCNSL. We investigate these agents combination determine tolerability synergistic efficacy. METHODS This is a phase 1b/2 study...
Abstract Background Alzheimer’s disease (AD) is an incurable neurodegenerative disorder and a major cause of dementia. Some the hallmarks AD include presence amyloid plaques in brain parenchyma, calcium dysregulation within individual neurons, neuroinflammation. A promising therapeutic would reverse or stymie these pathophysiologies animal model AD. Methods We tested effect NB-02, previously known as DA-9803, novel multimodal therapeutic, on deposition, neuronal regulation neuroinflammation...