A5065677103- Cardiomyopathy and Myosin Studies
- Estrogen and related hormone effects
- Breast Cancer Treatment Studies
- Hedgehog Signaling Pathway Studies
- Ion channel regulation and function
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Mast cells and histamine
- Virus-based gene therapy research
- Cancer Treatment and Pharmacology
- Renal and related cancers
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Cardiovascular Effects of Exercise
- Epigenetics and DNA Methylation
- Growth Hormone and Insulin-like Growth Factors
- Cancer Risks and Factors
- RNA Research and Splicing
- Congenital Ear and Nasal Anomalies
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Business Strategy and Innovation
- Viral Infections and Immunology Research
- Cancer Diagnosis and Treatment
Michigan State University
2020-2024
Dartmouth College
2001-2024
Northwell Health
2023-2024
ORCID
2023-2024
Stanford University
2023-2024
Corewell Health
2023-2024
University of North Carolina at Chapel Hill
2019-2023
Nottingham University Hospitals NHS Trust
1986-2022
Center for Autism and Related Disorders
2020-2021
University of Arizona
2014-2019
Previous research has linked stress with adverse health change; however, the immunologic mechanisms mediating these changes remain poorly understood. To test whether "stress" was associated alterations in cell-mediated immunity, we examined correlations of self-reported life change (LCS) and psychiatric symptoms natural killer cell activity (NKCA) among 114 healthy undergraduate volunteers. Although bivariate correlation between LCS NKCA not significant, subjects reporting few psychologic...
Developing neurons must regulate morphology, intrinsic excitability, and synaptogenesis to form neural circuits. When these processes go awry, disorders, including autism spectrum disorder (ASD) or epilepsy, may result. The phosphatase Pten is mutated in some patients having ASD seizures, suggesting that its mutation disrupts neurological function part through increasing neuronal activity. Supporting this idea, knock-out of mice can cause macrocephaly, behavioral changes similar ASD,...
Significance The cardiac thin filament (CTF) is a complex and highly dynamic multiprotein that regulates heart function at the molecular level. Mutations in proteins comprise cause cardiomyopathic remodeling due, part, to dysregulation of Ca 2+ binding. Many known mutations multiple occur significant physical distance from binding domain; thus, elucidation mechanisms has been challenging. We have developed now apply an atomistic model CTF this question obtained insight both provides disease...
The practise of Immediate Breast Reconstruction (IBR) following mastectomy for primary breast cancer is being increasingly adopted. Here the impact IBR on disease progression and survival was assessed treatment invasive cancer. 1697 consecutive patients received surgical operable between January 1996 December 2007. Overall, 691 (41%) whom 136 (20%) underwent (82 Latissimus Dorsi, 54 Subpectoral). effect overall survival, local distant recurrence analysed in all studied also separately within...
Retroviruses expressing a fluorescent protein, Cas9, and small guide RNA are used to mimic nonsense PTEN mutations from autism patients in developing mouse neurons. We compare the cellular phenotype elicited by CRISPR-Cas9 those using shRNA or Cre/Lox technologies find that knockdown knockout (KO) produced corresponding moderate severe neuronal hypertrophy all cells. In contrast, Cas9 approach missense Pten mutations, resulting mix of KO-equivalent hypertrophic wild type-like phenotypes....
A key role of chromatin kinases is to phosphorylate histone tails during mitosis spatiotemporally regulate cell division. Vaccinia-related kinase 1 (VRK1) a serine-threonine that phosphorylates H3 threonine 3 (H3T3) along with other chromatin-based targets. While structural studies have defined how several classes histone-modifying enzymes bind and function on nucleosomes, the mechanism engagement by largely unclear. Here, we paired cryo-electron microscopy biochemical cellular assays...
Ion channels are key determinants of membrane excitability. The actin cytoskeleton has a central role in morphology, migration, intracellular transport, and signaling. In this article, we show that the actin-binding protein cortactin regulates potassium channel Kv1.2 thereby provides direct link between dynamics previous reports, showed tyrosine phosphorylation-mediated suppression ionic current occurs by endocytosis protein. Pull-down assays using recombinant-purified demonstrated their...
The potassium channel Kv1.2 α-subunit is expressed in cerebellar Purkinje cell (PC) dendrites where its pharmacological inhibition increases excitability (Khavandgar et al., 2005). also basket (BC) axon terminals (Sheng 1994), blockade BC of PCs (Southan and Robertson, 1998a). Secretin receptors are both PC (for review, see (Yuan 2011). effect secretin on not yet known, but, like inhibitors, potently inhibitory input to (Yung 2001). This suggests may act part by suppressing Kv1.2....
Kv1.2 is a member of the Shaker family voltage-sensitive potassium channels and contributes to regulation membrane excitability. The electrophysiological activity undergoes tyrosine kinase-dependent suppression in process involving RhoA. We report that RhoA elicits ionic current by modulating channel endocytosis. This occurs through two distinct pathways, one clathrin-dependent other cholesterol-dependent. Activation Rho kinase (ROCK) via lysophosphatidic acid (LPA) receptor endocytosis...
The progression of genetically inherited cardiomyopathies from an altered protein structure to clinical presentation disease is not well understood. One the main roadblocks mechanistic insight remains a lack high-resolution structural information about multiprotein complexes within cardiac sarcomere. example tropomyosin (Tm) overlap region thin filament that crucial for function To address this central question, we devised coupled experimental and computational modalities characterize...
Autism spectrum disorder (ASD) manifests early in childhood. While genetic variants increase risk for ASD, a growing body of literature has established that utero chemical exposures also contribute to ASD risk. These chemicals include air-based pollutants like diesel particulate matter (DPM). A combination single-cell and direct transcriptomics DPM-exposed human-induced pluripotent stem cell-derived cerebral organoids revealed toxicogenomic effects DPM exposure during fetal brain...
Abstract This study investigates a series of factors, all recordable by the time presentation distant metastases from primary breast cancer and relates these to survival after initiation endocrine therapies. One hundred ninety-one patients have received therapy as initial treatment for metastases. In both histological grade oestrogen receptor (ER) status tumour tissue; lymph node stage menopausal at mastectomy disease-free interval sites are available analysis. Four factors been found...
Replication defective lentiviruses or retroviruses are capable of stably integrating transgenes into the genome an infected host cell.This technique has been widely used to encode fluorescent proteins, opto-or chemo-genetic controllers cell activity, heterologous expression human genes in model organisms.These viruses have also successfully deliver recombinases relevant target sites transgenic animals, even small hairpin micro RNAs order manipulate gene expression.While these techniques...
This report reveals the electrophysiological mechanisms of a movement disorder animal model with monoallelic Gnao1 loss. study illustrates role Gα o protein in regulating GABA release mouse cerebellum. could also facilitate discovery new drugs or drug repurposing for GNAO1-associated disorders. Moreover, since GNAO1 shares pathways other genes related to disorders, developing treatment disorders further pharmacological intervention monogenic
RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. While the role of genes have been well studied in cancer, less is known about their function during neurodevelopment. There are many that work concert to regulate signaling, suggesting if common brain phenotypes could be discovered they a broad impact on other disorders caused by distinct genes. We assessed cellular molecular consequences hyperactivating pathway using two cell type previously implicated...