A5102734706- Alzheimer's disease research and treatments
- Tuberous Sclerosis Complex Research
- Epilepsy research and treatment
- Chemokine receptors and signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- 14-3-3 protein interactions
- Histiocytic Disorders and Treatments
- Immune cells in cancer
- Eosinophilic Disorders and Syndromes
- Bone Metabolism and Diseases
- Wound Healing and Treatments
- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Pharmacological Effects and Toxicity Studies
- Tryptophan and brain disorders
- Advanced biosensing and bioanalysis techniques
- Advanced Biosensing Techniques and Applications
- Glioma Diagnosis and Treatment
- Tumors and Oncological Cases
- Biosensors and Analytical Detection
- Microtubule and mitosis dynamics
UConn Health
2022
Cleveland Clinic
2008-2021
National Heart Lung and Blood Institute
2006-2021
National Institutes of Health
2006-2021
Cleveland Clinic Lerner College of Medicine
2008-2017
Uniformed Services University of the Health Sciences
2008
National Cancer Institute
2006
Neurofibrillary tangles likely cause neurodegeneration in Alzheimer's disease (AD). We demonstrate that the CX3CL1 C-terminal domain can upregulate neurogenesis, which may ameliorate neurodegeneration. Here we generated transgenic (Tg-CX3CL1) mice by overexpressing neurons. Tg-CX3CL1 exhibit enhanced neurogenesis both subgranular and subventricular zones. This correlates well with elevated expression of TGF-β2 TGF-β3, activation their downstream signaling molecule Smad2. Intriguingly, adult...
Rationale: Lymphangioleiomyomatosis (LAM), occurring sporadically (S-LAM) or in patients with tuberous sclerosis complex (TSC), results from abnormal proliferation of LAM cells exhibiting mutations loss heterozygosity (LOH) the TSC genes, TSC1 TSC2.Objectives: To identify molecular markers useful for isolating body fluids and determine frequency TSC2 LOH.Methods: Candidate cell surface were identified using gene microarray analysis human TSC2−/− cells. Cells bronchoalveolar lavage fluid...
The membrane-anchored CX3CL1 is best known to exert its signaling function through binding receptor CX3CR1. This study demonstrates a novel that exerts. sequentially cleaved by α-, β-, and γ-secretase, the released intracellular domain (CX3CL1-ICD) would translocate into cell nucleus alter gene expression due this back-signaling function. Amyloid deposition neuronal loss were significantly reduced when C-terminal fragment (CX3CL1-ct) was overexpressed in Alzheimer’s 5xFAD mouse model....
ADP-ribosylation factors (ARFs) are critical in vesicular trafficking. Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG)1 and BIG2 activate ARFs by accelerating replacement of bound GDP with GTP. Additional differing functions these ≈200-kDa proteins now being recognized, as their independent intracellular movements. Here, we describe the localization COS7 cells immunofluorescence microscopy BIG2, but not BIG1, structures that have characteristics recycling endosomes during...
Patients with tuberous sclerosis complex (TSC) develop hamartomas containing biallelic inactivating mutations in either TSC1 or TSC2, resulting mammalian target of rapamycin (mTOR) activation. Hamartomas overgrow epithelial and mesenchymal cells TSC skin. The pathogenetic mechanisms for these changes had not been investigated, the existence location ("two-hit" cells) was unclear. We compared skin (angiofibromas periungual fibromas) normal-appearing same patient, we observed more...
Amyloid precursor protein (APP) is cleaved by gamma-secretase to simultaneously generate amyloid beta (Aβ) and APP Intracellular Domain (AICD) peptides. Aβ plays a pivotal role in Alzheimer's disease (AD) pathogenesis but recent studies suggest that amyloid-independent mechanisms also contribute the disease. We previously showed AICD transgenic mice (AICD-Tg) exhibit AD-like features such as tau pathology, aberrant neuronal activity, memory deficits neurodegeneration an age-dependent manner....
CX3CL1, also known as fractalkine, is best for its signaling activity through interactions with cognate receptor CX3CR1. However, intrinsic function that independent of interaction CX3CR1 remains to be fully understood. We demonstrate the intracellular domain CX3CL1 (CX3CL1-ICD), generated upon sequential cleavages by α-/β-secretase and γ-secretase, initiates a back activity, which mediates direct signal transmission gene expression in nucleus. To study this, we fused synthetic peptide...
BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for disease. In examining BACE1-null mice, we discovered that deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly subpial zone (SPZ). Such were rarely observed wild-type SPZ not reported other mouse models. To understand their origins fates, examined how neuroblasts mature migrate during early postnatal development. We show such are...
Amyloid-ß peptides (Aß), derived from amyloid precursor protein (APP), have been implicated to play a pivotal role in Alzheimer's disease (AD) pathogenesis. However, there is increasing evidence that AD etiology complex and multifactorial, amyloid-independent mechanisms can also contribute the disease. Identification characterization of such crucial order formulate an effective therapy against AD. APP Intracellular domain (AICD) small cytoplasmic fragment APP, which generated simultaneously...