A5072335433- Social and Educational Sciences
- Epigenetics and DNA Methylation
- Ovarian cancer diagnosis and treatment
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Organ Transplantation Techniques and Outcomes
- Bacterial Genetics and Biotechnology
- MicroRNA in disease regulation
- Supramolecular Self-Assembly in Materials
- Metabolomics and Mass Spectrometry Studies
- Enzyme Structure and Function
- Renal cell carcinoma treatment
- Parkinson's Disease Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Liver Disease and Transplantation
- Crystallization and Solubility Studies
- Cancer Genomics and Diagnostics
- Drug Transport and Resistance Mechanisms
- X-ray Diffraction in Crystallography
- Themes in Literature Analysis
- Amyotrophic Lateral Sclerosis Research
- Crystallography and molecular interactions
- Historical and Archaeological Studies
Umeå University
2011-2024
Brigham and Women's Hospital
2013-2023
Harvard University
2013-2023
Brown University
2021-2022
Rhode Island Hospital
2021-2022
Providence College
2022
Facial Plastics Surgery Associates
2017
Women's Hospital
2015
Clark University
2009-2011
École Polytechnique Fédérale de Lausanne
2007
Highlights•PAX8 can drive murine high-grade serous tumors originating in the fallopian tube•Early alterations Brca, Tp53, and Pten lead to intraepithelial precursor lesions•Genomic analysis of Pax8-driven shows strong correlation with human tumors•High-grade ovarian cancer arise from tubal secretory cellSummaryHigh-grade carcinoma presents significant clinical therapeutic challenges. Although traditional model carcinogenesis has focused on ovary as a tumor initiation site, recent studies...
Alzheimer disease is a neurodegenerative disorder that tightly linked to the self-assembly and amyloid formation of 39–43-residue-long amyloid-β (Aβ) peptide. Considerable evidence suggests correlation between development longer variants peptide, Aβ-(1–42/43). Currently, molecular understanding for this behavior lacking. In present study, we have investigated hydrogen/deuterium exchange Aβ-(1–42) fibrils under physiological conditions, using solution NMR spectroscopy. The obtained...
A procedure for NMR analysis of the human saliva metabolome, that can differentiate dementia patients from matched controls and identify discriminatory metabolites, is described.
Alzheimer's disease is linked to a pathological polymerization of the endogenous amyloid β-peptide (Aβ) that ultimately forms plaques within human brain. We used surface plasmon resonance (SPR) measure kinetic properties Aβ fibril formation under different conditions during process. For all processes, critical concentration free monomers, as defined by dissociation equilibrium constant (KD), required for buildup polymer, example, fibrils. At concentrations below KD, cannot occur. However, KD...
Abstract Purpose: A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at level epigenetic regulation. Experimental Design: We evaluated potential using global loss 5-hydroxymethylcytosine (5-hmC) levels as novel diagnostic and prognostic marker to better assess chemotherapy response outcome high-grade serous tumors (HGSOC), most common deadliest subtype ovarian cancer. Furthermore, we identified...
Detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for lesions and potentially low levels these markers. The current study systematically develops an extracellular-vesicle (EV)-based test detection, specifically focusing on high-grade serous ovarian carcinoma (HGSOC). marker selection based emerging insights into HGSOC pathogenesis, notably that it arises from precursor within fallopian tube. This work thus establishes murine tube (mFT) cells...
The human plasma protein transthyretin (TTR) may form fibrillar deposits that are associated with both inherited and idiopathic amyloidosis. present study utilizes solution nuclear magnetic resonance spectroscopy, in combination hydrogen/deuterium exchange, to determine residue-specific solvent protection factors within the structure of clinically relevant variant, TTRY114C. This novel approach suggests a fibril core comprised six β-strands, A-B-E-F-G-H, which retains native-like...
AD (Alzheimer's disease) is a neurodegenerative disorder characterized by self-assembly and amyloid formation of the 39–43 residue long Aβ (amyloid-β)-peptide. The most abundant species, Aβ(1–40) Aβ(1–42), are both present within senile plaques, but Aβ(1–42) peptides considerably more prone to self-aggregation also essential for development AD. To understand molecular pathological mechanisms behind AD, detailed knowledge structures Aβ-peptides vital. In study we have used quenched...
In membranes of Acholeplasma laidlawii two consecutively acting glucosyltransferases, the (i) α-monoglucosyldiacylglycerol (MGlcDAG) synthase (alMGS) (EC2.4.1.157) and (ii) α-diglucosyl-DAG (DGlcDAG) (alDGS) (EC 2.4.1.208), are involved in maintaining a certain anionic lipid surface charge density constant nonbilayer/bilayer conditions (curvature packing stress), respectively. Cloning alDGS gene revealed related uncharacterized sequence analogs especially several Gram-positive pathogens,...
The complexity and heterogeneity of ovarian cancer cases are difficult to reproduce in
Abstract The neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) share some common molecular deficits including disruption of protein homeostasis leading to disease-specific aggregation. While insoluble aggregates are the defining pathological confirmation diagnosis, patient stratification based on early etiologies may identify distinct subgroups within a clinical diagnosis that would respond differently in therapeutic development programs. We...
Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol its metabolites. Here we describe detail a methodology for the identification quantification of multiple sterols including oxysterols sterol-acids found these fluids. The method is translatable to any laboratory with access liquid chromatography – tandem mass spectrometry. exploits isotope-dilution spectrometry absolute target applicable semi-quantification other which isotope labelled surrogates not available approximate...
Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-beta peptide (Abeta). Divalent metal ions such as Cu(2+) Zn(2+) are known to significantly affect rate morphology Abeta assemblies in vitro also found at elevated levels within cerebral plaques vivo. The present investigation characterized architecture aggregated forms Abeta(1-40) Abeta(1-42) presence or absence either using quenched...
Chloroplast membranes contain a substantial excess of the nonbilayer-prone monogalactosyldiacylglycerol (GalDAG) over biosynthetically consecutive, bilayer-forming digalactosyldiacylglycerol (GalGalDAG), yielding high membrane curvature stress. During phosphate shortage, plants replace phospholipids with GalGalDAG to rescue while maintaining homeostasis. Here we investigate how activity corresponding glycosyltransferase (GT) in Arabidopsis thaliana (atDGD2) depends on local bilayer...
We showed that the genetically engineered carrier-protein albebetin and its biologically active constructs with interferon-α2 octapeptide LKEKKYSP or differentiation factor hexapeptide TGENHR are inherently highly amyloidogenic at physiological pH. The kinetics of fibrillation were monitored by thioflavine-T (ThT) binding morphological changes atomic force microscopy. Fibrillation proceeds via multiple pathways includes a hierarchy amyloid structures ranging from oligomers to protofilaments...
Identifying factors that affect the self-assembly of Aβ (amyloid-β peptide) is utmost importance in quest to understand molecular mechanisms causing AD (Alzheimer's disease). Ca2+ has previously been shown accelerate both fibril nucleation and maturation, dysregulated homoeostasis frequently correlates with development AD. The regarding binding, as well its effect on kinetics, are not fully understood. Using a polymerization assay we show dynamic reversible manner enhances elongation rate...
Talazoparib, a potent PARP inhibitor, induces synthetic lethality in BRCA-deficient cancers making it an attractive candidate for ovarian cancer treatment. However, its potency lends itself to side effects associated more closely with traditional chemotherapeutics than other clinically approved inhbitors. We sought formulate Talazoparib nanoparticle delivery system, which allows the drug be administered intraperitoneally. This was done specifically target peritoneal dissemination of late...
Differentiating between Parkinson's disease (PD) and the atypical Parkinsonian disorders of multiple system atrophy (MSA) progressive supranuclear palsy (PSP) is difficult clinically due to overlapping symptomatology, especially at early stages. Consequently, there a need identify metabolic markers for these diseases develop them into viable biomarkers. In present investigation, solution nuclear magnetic resonance mass spectrometry metabolomics were used quantitatively characterize plasma...