A5043450539- Hippo pathway signaling and YAP/TAZ
- Amyotrophic Lateral Sclerosis Research
- Nerve injury and regeneration
- Wnt/β-catenin signaling in development and cancer
- Parkinson's Disease Mechanisms and Treatments
- Histone Deacetylase Inhibitors Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Lipid metabolism and biosynthesis
- Neurogenesis and neuroplasticity mechanisms
- biodegradable polymer synthesis and properties
- Prenatal Substance Exposure Effects
- FOXO transcription factor regulation
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Pulmonary Hypertension Research and Treatments
- Synthetic Organic Chemistry Methods
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Ubiquitin and proteasome pathways
- Autism Spectrum Disorder Research
Massachusetts General Hospital
2015-2020
MaineGeneral Medical Center
2016-2018
Harvard University
2016
Boston Children's Hospital
2014
The Hippo signaling pathway has been implicated in mammalian organ size regulation and tumor suppression. Specifically, the plays a critical role regulating activity of transcriptional coactivator Yes-associated protein (YAP), which modulates proliferative program. Recent investigations have demonstrated that while this is activated quiescent livers, its inhibition leads to liver overgrowth tumorigenesis. However, during natural process regeneration remains unknown. Here we investigated...
Abstract The Hippo signaling pathway is involved in organ size regulation and tumor suppression. Although inhibition of leads to tumorigenesis, activation may play a role neurodegeneration. Specifically, the upstream regulator, mammalian sterile 20 (STE20)-like kinase 1 (MST1), reduces activity transcriptional co-activator Yes-Associated Protein (YAP), thereby mediating oxidative stress-induced neuronal death. Here, we investigated possible this Huntington’s disease (HD) pathogenesis. Our...
Pediatric hepatocellular carcinoma (HCC) is a rare tumor which associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown play role in hepatocyte proliferation development HCC animal models. Therefore, we sought examine activity YAP expression components non-neoplastic liver tissue from 7 pediatric patients moderately differentiated HCC. None had...
Abstract Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated an increase microgliosis astrogliosis lumbar spinal cord SOD1 G93A transgenic mice before onset symptoms, a response which correlated with disease progression. Importantly, early stage homeostatic microglia enhanced motor neuron survival, while pro-inflammatory were toxic to neurons mice. Recent...
The hPFN1G118V mouse model, overexpressing mutant human profilin1 linked to a rare form of ALS, was comprehensively characterized assess its suitability for preclinical drug testing. Using large cohort nearly 250 transgenic and wild-type mice in longitudinal study, we combined behavioral, electrophysiological, neuropathological assessments define the chronology pathological events inherent subject variability. early stage disease this model by elevated plasma neurofilament light chain...
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease caused by loss of motor neurons. ALS patients experience rapid deterioration in muscle function with an average lifespan 3–5 years after diagnosis. Currently, the most effective therapeutic only extends few months, thus highlighting need for new and improved therapies. Neurotrophic factors (NTFs) are important neuronal development, maintenance, survival. NTF treatment has previously shown efficacy pre-clinical models....
The exact mechanisms underlying neuroinflammation and how they contribute to amyotrophic lateral sclerosis (ALS) pathogenesis remain unclear. One possibility is the secretion of neurotoxic factors, such as lipocalin-2 (LCN2), that lead neuronal death.LCN2 levels were measured in human postmortem tissue using Western blot, quantitative real time polymerase chain reaction, immunofluorescence, plasma by enzyme-linked immunosorbent assay. SH-SY5Y cells used test pro-inflammatory effects...
Prenatal cocaine exposure remains a major public health concern because of its adverse effects on cognitive function. Although the molecular mechanisms underlying impairment are not fully understood, brain-derived neurotrophic factor (BDNF) signaling via receptor tyrosine kinase B (TrkB) is emerging as potential candidate. We used mouse model to examine impact ongoing BDNF expression in dorsal forebrain embryonic day 15 (E15) well long-term prenatal BDNF-TrkB frontal cortex early postnatal...
X-linked Dystonia-Parkinsonism (XDP) is a neurodegenerative disease linked to an insertion of SINE-VNTR-Alu (SVA)-type retrotransposon within intron TAF1 . This SVA induces aberrant splicing and partial retention, thereby decreasing levels the full-length transcript. Here we sought determine if these altered transcriptional dynamics caused by are also accompanied local changes in histone acetylation, given that modifications influence gene expression. Because protein may itself exhibit...
There is an unmet need for mechanism-based biomarkers and effective disease modifying treatments in amyotrophic lateral sclerosis (ALS). Previous findings have provided evidence that histone deacetylases (HDAC) are altered ALS, providing a rationale testing HDAC inhibitors as therapeutic option.We measured class I II protein transcript levels together with acetylation of downstream substrates by using Western blotting postmortem tissue ALS controls. [11 C]Martinostat, novel positron emission...
Prenatal cocaine exposure remains a major public health concern because of its adverse impact on cognitive function in children and adults. We report that prenatal produces significant deficits reversal learning, key component flexibility, mouse model. used an olfactory learning paradigm found the prenatally cocaine-exposed mice showed marked failure to learn reversed paradigm. Because brain-derived neurotrophic factor (BDNF) is regulator functions, increases expression BDNF phosphorylated...
Abstract Purpose: Currently, there is no effective chemotherapy for the treatment of hepatocellular carcinoma (HCC). Both HCC and hepatoblastoma (HB) remain lethal in their metastatic forms. Therefore, understanding molecular mechanisms tumor survival proliferation critical developing novel therapies. Our lab has shown that YAP, a transcription factor, involved liver regeneration. Specifically, increases nuclear YAP have been coupled with expression genes important cell proliferation. We...