- Nerve injury and regeneration
- Retinoids in leukemia and cellular processes
- Pain Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Genomics, phytochemicals, and oxidative stress
- Axon Guidance and Neuronal Signaling
- Pluripotent Stem Cells Research
- Peroxisome Proliferator-Activated Receptors
- Estrogen and related hormone effects
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Hereditary Neurological Disorders
- Calpain Protease Function and Regulation
- Tuberous Sclerosis Complex Research
- Signaling Pathways in Disease
- Neuroscience of respiration and sleep
- PI3K/AKT/mTOR signaling in cancer
- Toxin Mechanisms and Immunotoxins
- Lipid Membrane Structure and Behavior
- Transgenic Plants and Applications
- Drug Transport and Resistance Mechanisms
- Cellular transport and secretion
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Kruppel-like factors research
University of California, San Diego
2011-2024
Sapienza University of Rome
2016
Chiba University
2016
Sequenom (United States)
2004
University of Kentucky
1995-2003
Scripps Research Institute
2001
University of Nevada, Reno
1990
Tuberous sclerosis (TSC) is a genetic disorder that results in the development of hamartomatous lesions variety organ systems. Both prevalence disease and often devastating consequences these tumors pose serious health medical care problem. The has been mapped to two distinct loci humans, although genes (<i>TSC1</i> and<i>TSC2</i>) for both have recently cloned, their function remains an enigma. Data presented here demonstrates TSC2 protein can bind selectively modulate transcription...
Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Herein, we show that deletion LDL receptor-related protein-1 (LRP1) gene (scLRP1 −/− ) induces abnormalities axon ensheathment nonmyelinating Remak bundles. These anatomical changes were associated with mechanical allodynia, even absence injury. In response to crush injury, sciatic nerves scLRP1 mice showed accelerated degeneration cell death. Remyelinated evident 20 d after injury...
In peripheral nerve injury, Schwann cells (SCs) must survive to exert a continuing and essential role in successful regeneration. Herein, we show that injury is associated with activation of endoplasmic reticulum (ER) stress the adaptive unfolded protein response (UPR). The UPR culminates expression C/EBP homology (CHOP), proapoptotic transcription factor SCs, unless counteracted by LDL receptor-related protein-1 (LRP1), which serves as major activator phosphatidylinositol 3-kinase (PI3K)....
Low-density lipoprotein receptors (LRPs) are present extensively on cells outside of the nervous system and classically exert roles in metabolism. It has been reported recently that LRP1 activation could phosphorylate neurotrophin receptor TrkA PC12 increase neurite outgrowth from developing cerebellar granule cells. These intriguing findings led us to explore hypothesis would activate canonical neurotrophic factor signaling adult neurons promote axonal regeneration after spinal cord injury....
Abstract Sensory neurons in the PNS demonstrate substantial capacity for regeneration following injury. Recent studies have identified changes transcriptome of sensory neurons, which are instrumental axon regeneration. The role Schwann cells (SCs) mediating these remains undefined. We tested hypothesis that SCs regulate expression genes before and after injury by comparing mice LDL Receptor‐related Protein‐1 ( LRP1 ) is deleted (scLRP1 −/− mice) with wild‐type +/+ littermates. an endocytic...
In the peripheral nervous system, Schwann cells (SCs) demonstrate surveillance activity, detecting injury and undergoing trans-differentiation to support repair. SC receptors that detect system remain incompletely understood. We used RT-PCR profile ionotropic glutamate receptor expression in cultured SCs. identified subunits required for assembly of N-methyl-D-aspartic acid (NMDA) (NMDA-Rs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors, kainate receptors. Treatment SCs with...
Schwann cells (SCs) detect injury to peripheral nerves and transform phenotypically respond facilitate repair. Cell-signaling pathways changes in gene expression that drive SC phenotypic transformation have been described; however, the receptors nervous system (PNS) not identified. LDL receptor-related protein 1 (LRP1) is a receptor for numerous ligands, including intracellular proteins released by injured components of degenerated myelin. In certain cell types, SCs, LRP1 cell-signaling...
Developing sensory neurons require neurotrophic support for survival, neurite outgrowth and myelination. The low-density lipoprotein receptor-related protein-1 (LRP1) transactivates Trk receptors thereby functions as a putative neurotrophin. Herein, we show that LRP1 is abundantly expressed in developing dorsal root ganglia (DRG) LRP1-dependent cell signaling supports extension receptivity to Schwann cells even the absence of neurotrophins. Cultured embryonic DRG (E15) were treated with...
The mechanisms by which peroxisome proliferators are able to regulate metabolic processes such as fat metabolism, whileat the same time creating an environment for development of hepatocellular carcinomas, is a central issue in non-genotoxic carcinogenesis field. convergence two members steroid receptor family (peroxisome proliferator-activated receptor, PPAR; and retinold X RXR) has provided strong support oxidative stress component this process, but yet define clearly pathway classical...
In eukaryotic organisms gene expression is regulated through a variety of upstream transacting factors (transcription factors) whose primary function appears to be the targeting coregulatory protein complexes, which interact with basal transcription machinery define relative rate for specific gene. Understanding regulatory forces mediating factor activity has been focus both academic and industrial research efforts over past 15 yr, in this time frame methodologies have developed...
Abstract Background Early‐onset Alzheimer’s disease (EOAD) is a complex that occurs at an early age onset (AAO) before 65 years, constituting 5‐6% of all AD cases and remains poorly understood. Patient‐derived induced pluripotent stem cells (iPSCs) have been used to model different forms EOAD display heterogeneous mechanisms. Method We examined iPSC‐derived neurons from both familial harboring mutations in PSEN1 A79V , PSEN2 N141I APP V717I non‐familial patients AAO. RNA‐seq for as well...
Members of the steroid/hormone nuclear receptor superfamily regulate target gene transcription via recognition and association with specific cis-acting sequences DNA, called hormone response elements (HREs). The identification novel HREs is fundamental to understanding physiological function receptor-mediated signalling pathways. A number these receptors are transcriptionally active, or can be induced an active state, when expressed in yeast strain Saccharomyces cerevisiae. This aspect...
Abstract Non-familial Alzheimer’s disease (AD) occurring before 65 years of age is commonly referred to as early-onset (EOAD) and constitutes ~ 5–6% all AD cases (Mendez et al. in Continuum 25:34–51, 2019). While EOAD exhibits the same clinicopathological changes such amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, cognitive decline (Sirkis Mol Psychiatry 27:2674–88, 2022; Caldwell Brain 15:83, 2022) observed more prevalent late-onset (LOAD), patients tend have severe...