A5054013645- Spinal Cord Injury Research
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Hypothalamic control of reproductive hormones
- Signaling Pathways in Disease
- Nerve injury and regeneration
- Ion Channels and Receptors
- Cardiomyopathy and Myosin Studies
- Epigenetics and DNA Methylation
- Plant Molecular Biology Research
- Genomics and Chromatin Dynamics
- Ovarian function and disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Neonatal and fetal brain pathology
- Circular RNAs in diseases
- Neuroendocrine regulation and behavior
- Plant Reproductive Biology
- Surfactants and Colloidal Systems
- Nitric Oxide and Endothelin Effects
- Genetics and Physical Performance
- RNA regulation and disease
- Traditional and Medicinal Uses of Annonaceae
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
James J. Peters VA Medical Center
2017-2024
Icahn School of Medicine at Mount Sinai
2017-2024
Virginia Tech
2023
Oregon National Primate Research Center
2015-2021
United States Department of Veterans Affairs
2021
Oregon Health & Science University
2015-2018
Austral University of Chile
2010-2015
ZRT Laboratory
2015
University of Chile
2005-2008
Abstract Puberty is regulated by epigenetic mechanisms and highly sensitive to metabolic nutritional cues. However, the pathways mediating effects of nutrition obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as molecule that restrains female puberty via repression puberty-activating gene, Kiss1 . SIRT1 expressed in hypothalamic neurons suppresses expression. interacts with Polycomb silencing complex decrease promoter activity. As...
Huntington's disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is powerful antioxidant highly concentrated the brain where it acts as messenger, modulating neuronal metabolism. Using an electrophysiological approach R6/2 HD slices, we observe abnormal ascorbic flux from astrocytes to neurons, which responsible for alterations metabolic substrate preferences. Here using striatal neurons derived knock-in mice expressing mutant huntingtin...
The identification of loss-of-function mutations in MKRN3 patients with central precocious puberty association the decrease expression medial basal hypothalamus mice before initiation reproductive maturation suggests that is acting as a brake on gonadotropin-releasing hormone (GnRH) secretion during childhood. In current study, we investigated mechanism by which prevents premature manifestation pubertal process. We showed that, mice, high rats and nonhuman primates early life, decreases...
Abstract In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger ( ZNF ) genes in timing human puberty. Here we show that hypothalamic expression several s decreased agonadal male monkeys association with pubertal reactivation gonadotropin secretion. Expression two these s, GATAD1 and ZNF573 , also decreases peripubertal female monkeys. However, only abundance increases when secretion...
Polycomb group (PcG) proteins control the timing of puberty by repressing Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Here we identify two members Trithorax (TrxG) modifiers, mixed-lineage leukemia 1 (MLL1), and 3 (MLL3), as central components an activating epigenetic machinery that dynamically counteracts PcG repression. Preceding puberty, MLL1 changes chromatin configuration at promoters Tac3, genes required for to occur, from repressive permissive. Concomitantly, MLL3...
Abstract Population studies elucidating the genetic architecture of reproductive ageing have been largely limited to European ancestries, restricting generalizability findings and overlooking possible key genes poorly captured by common variation. Here, we report 26 loci (all P < 5 × 10 –8 ) for ageing, i.e. puberty timing or age at menopause, in a non-European population (up 67,029 women Japanese ancestry). Highlighted menopause include GNRH1 , which supports primary, rather than...
Abstract Female puberty is subject to Polycomb Group (PcG)-dependent transcriptional repression. Kiss1 , a puberty-activating gene, key target of this silencing mechanism. Using gain-of-function approach and systems biology strategy we now show that EED, an essential PcG component, acts in the arcuate nucleus hypothalamus alter functional organization gene network involved stimulatory control puberty. A central node Kdm6b which encodes enzyme erases PcG-dependent histone modification...
Spinal cord injury (SCI) results in rapid muscle loss. Exogenous molecular interventions to slow atrophy after SCI have been relatively ineffective and require the search for novel therapeutic targets. Connexin hemichannels (CxHCs) allow nonselective passage of small molecules into out cell. Boldine, a CxHC-inhibiting aporphine found boldo tree (
Membrane channels such as those formed by connexins (Cx) and P2X 7 receptors (P2X R) are permeable to calcium ions other small molecules adenosine triphosphate (ATP) glutamate. Release of ATP glutamate through these is a key mechanism driving tissue response traumas spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx Panx1 hemichannels (HCs). To test if boldine could improve function after SCI, or vehicle was administered treat mice with...
Background The cold and menthol receptor, TRPM8, is a non-selective cation channel expressed in subset of peripheral neurons that responsible for neuronal detection environmental stimuli. It was previously shown members the transient receptor potential (TRP) family ion channels are translocated toward plasma membrane (PM) response to agonist stimulation. Because spatial temporal dynamics cell-surface residence may determine activity, we hypothesized movement TRPM8 from PM might be regulated...
The spatial and temporal distribution of receptors constitutes an important mechanism for controlling the magnitude cellular responses. Several members transient receptor potential (TRP) ion channel family can regulate their function by modulating expression at plasma membrane (PM) through rapid vesicular translocation fusion. mechanisms underlying this regulation are not completely understood, contribution trafficking to physiological is unknown. TRPM8 expressed in mammalian peripheral...
Peripheral nerve injury often results in poor functional recovery due to a prolonged period of muscle denervation. In particular, absent axonal contact, denervated can undergo irrevocable atrophy and diminished receptiveness for reinnervation over time, ultimately reducing the likelihood meaningful neuromuscular recovery. While innovative surgical approaches minimize harmful effects denervation by re-routing neighboring—otherwise uninjured—axons, there are no clinically-available preserve...
Traumatic spinal cord injury (SCI) results in wide-ranging cellular and systemic dysfunction the acute chronic time frames after injury. Chronic SCI has well-described secondary medical consequences while unique metabolic challenges as a result of physical trauma, in-patient recovery other post-operative outcomes. Here, we used high resolution mass spectrometry approaches to describe circulating lipidomic metabolomic signatures using blood serum from mice 7 d complete SCI. Additionally,...
Spinal cord injury (SCI) is a devastating form of neurotrauma. Patients who carry one or two apolipoprotein E (ApoE)4 alleles show worse functional outcomes and longer hospital stays after SCI, but the cellular molecular underpinnings for this genetic link remain poorly understood. Thus, there great need to generate animal models accurately replicate determinants SCI spur development treatments that improve physical function. Here, we examined moderate contusion transgenic mice expressing...
Abstract Axonal regeneration in the mature CNS is limited by extracellular inhibitory factors. Triple knockout mice lacking major myelin-associated inhibitors do not display spontaneous after injury, indicating presence of other inhibitors. Searching for such inhibitors, we have detected elevated levels histone H3 human CSF 24 h spinal cord injury. Following dorsal column lesions and optic nerve crushes rats, were at injury site. Similar to these histones induced growth cone collapse...