Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.
Journal of Hepatology 65(2):325 (2016)
Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability ...
Novel lean type 2 diabetic rat model using gestational low-protein programming.
American Journal of Obstetrics and Gynecology 214(4):540.e1 (2016)
Type 2 diabetes (T2D) in lean individuals is not well studied and up to 26% of diabetes occurs in these individuals. Although the cause is not well understood, it has been primarily attributed to nutritional issues during early development.
Our objective was to develop a lean T2D model using ges...
Ca2+ Binding/Permeation via Calcium Channel, CaV1.1, Regulates the Intracellular Distribution of the Fatty Acid Transport Protein, CD36, and Fatty Acid Metabolism.
Journal of Biological Chemistry 290(39):23751 (2015)
Ca(2+) permeation and/or binding to the skeletal muscle L-type Ca(2+) channel (CaV1.1) facilitates activation of Ca(2+)/calmodulin kinase type II (CaMKII) and Ca(2+) store refilling to reduce muscle fatigue and atrophy (Lee, C. S., Dagnino-Acosta, A., Yarotskyy, V., Hanna, A., Lyfenko, A., Knobl...
Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters.
PNAS 112(8):2343 (2015)
Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-...
Role of innate immunity and altered intestinal motility in LPS- and MnCl2-induced intestinal intussusception in mice.
American Journal of Physiology - Gastrointestin... 306(5):G445 (2014)
Intestinal intussusception (ISS) commonly causes intestinal obstruction in children. One mechanism that has been proposed to cause ISS is inflammation-induced alteration of intestinal motility. We investigated whether innate inflammatory factors or altered motility is required for induction of I...
Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow.
Molecular Neurodegeneration 9:28 (2014)
Accumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood-brain barrier and cerebral amyloid angiopathy (CAA) is a prominent f...
Increased expression of CYP24A1 correlates with advanced stages of prostate cancer and can cause resistance to vitamin D3-based therapies.
FASEB Journal 28(1):364 (2014)
A major limitation of exogenous vitamin D3 administration for the treatment of prostate cancer is the marginal, if any, clinical efficacy. We dissected the basis for the resistance to the vitamin D3 antitumor properties and specifically examined the effect of its major catabolic enzyme, CYP24A1,...
In vivo axonal transport deficits in a mouse model of fronto-temporal dementia.
NeuroImage: Clinical 4:711 (2014)
Axonal transport is vital for neurons and deficits in this process have been previously reported in a few mouse models of Alzheimer's disease prior to the appearance of plaques and tangles. However, it remains to be determined whether axonal transport is defective prior to the onset of neurodege...
Use of magnetization transfer contrast MRI to detect early molecular pathology in Alzheimer's disease.
Magnetic Resonance in Medicine 71(1):333 (2014)
The purpose of this study was to determine if magnetization transfer contrast (MTC) imaging could be used to detect early macromolecular accumulation in a mouse model of early Alzheimer's disease.
We obtained MTC images at 9.4 T at three different age points in the Tg2576 mouse model of Alzheime...
Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells.
Nanomedicine 9(8):1209 (2014)
We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer.
Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indoc...
Zic3 is required in the extra-cardiac perinodal region of the lateral plate mesoderm for left-right patterning and heart development.
Human Molecular Genetics 22(5):879 (2013)
Mutations in ZIC3 cause human X-linked heterotaxy and isolated cardiovascular malformations. A mouse model with targeted deletion of Zic3 demonstrates an early role for Zic3 in gastrulation, CNS, cardiac and left-right axial development. The observation of multiple malformations in Zic3(null) mi...
Tau loss attenuates neuronal network hyperexcitability in mouse and Drosophila genetic models of epilepsy.
Journal of Neuroscience 33(4):1651 (2013)
Neuronal network hyperexcitability underlies the pathogenesis of seizures and is a component of some degenerative neurological disorders such as Alzheimer's disease (AD). Recently, the microtubule-binding protein tau has been implicated in the regulation of network synchronization. Genetic remov...
Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury.
ACS Nano 6(9):8007 (2012)
Injury to the neurovasculature is a feature of brain injury and must be addressed to maximize opportunity for improvement. Cerebrovascular dysfunction, manifested by reduction in cerebral blood flow (CBF), is a key factor that worsens outcome after traumatic brain injury (TBI), most notably unde...
IκBα deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery.
Molecular Neurodegeneration 7:47 (2012)
The transcription factor NFκB is an important mediator of cell survival and inflammation in the immune system. In the central nervous system (CNS), NFκB signaling has been implicated in regulating neuronal survival following acute pathologic damage such as traumatic brain injury (TBI) and stroke...
Use of fluoroscopy to study in vivo motility in mouse pups.
Journal of Pediatric Gastroenterology and Nutri... 52(6):679 (2011)
Few methods exist to noninvasively study in vivo gastrointestinal motility in animal models of enteric infections. None have been used on mouse pups, which often display more severe symptoms during enteric infections than adult mice. This study sought to determine whether digital fluoroscopy cou...
R-flurbiprofen improves axonal transport in the Tg2576 mouse model of Alzheimer's disease as determined by MEMRI.
Magnetic Resonance in Medicine 65(5):1423 (2011)
Axonal pathology is a prevalent feature of Alzheimer's disease (AD) and is thought to occur predominantly due to the accumulation of amyloid beta (Aβ). However, it remains unclear whether therapeutics geared toward reducing Aβ improves axonal deficits. We have previously used Manganese Enhanced ...
Amyloid β-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide.
Journal of Neuroscience 31(15):5589 (2011)
Generation of reactive oxygen species (ROS) causes cellular oxidative damage and has been implicated in the etiology of Alzheimer's disease (AD). In contrast, multiple lines of evidence indicate that ROS can normally modulate long-term potentiation (LTP), a cellular model for memory formation. W...
Manganese-enhanced magnetic resonance imaging (MEMRI).
Methods in Molecular Biology 711:145 (2011)
The use of manganese ions (Mn(2+)) as an MRI contrast agent was introduced over 20 years ago in studies of Mn(2+) toxicity in anesthetized rats (1). Manganese-enhanced MRI (MEMRI) evolved in the late nineties when Koretsky and associates pioneered the use of MEMRI for brain activity measurements...
Manganese enhanced MRI (MEMRI): neurophysiological applications.
Reviews in the Neurosciences 22(6):675 (2011)
Manganese ion (Mn(2+)) is a calcium (Ca(2+)) analog that can enter neurons and other excitable cells through voltage gated Ca(2+) channels. Mn(2+) is also a paramagnetic that shortens the spin-lattice relaxation time constant (T(1)) of tissues where it has accumulated, resulting in positive cont...
Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo.
Nano Letters 10(12):4920 (2010)
Nanoparticle-based therapeutics with local delivery and external electromagnetic field modulation holds extraordinary promise for soft-tissue cancers such as breast cancer; however, knowledge of the distribution and fate of nanoparticles in vivo is crucial for clinical translation. Here we demon...