A5057140936- Protein Kinase Regulation and GTPase Signaling
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Parathyroid Disorders and Treatments
- Signaling Pathways in Disease
- Pain Mechanisms and Treatments
- Cell death mechanisms and regulation
- Melanoma and MAPK Pathways
- Spinal Cord Injury Research
- Treatment of Major Depression
- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Axon Guidance and Neuronal Signaling
- Nerve Injury and Rehabilitation
- Protein Tyrosine Phosphatases
- Ubiquitin and proteasome pathways
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Connective tissue disorders research
- Bone health and treatments
- Pharmacological Effects of Natural Compounds
- RNA regulation and disease
- Pulmonary Hypertension Research and Treatments
- Bone and Dental Protein Studies
- Developmental Biology and Gene Regulation
Massachusetts General Hospital
2008-2016
Harvard University
2008-2016
Center for Pain and the Brain
2012-2016
Center for Systems Biology
2009
Brigham and Women's Hospital
2009
Gordon Center for Medical Imaging
2008
Tufts University
1999-2005
Nagoya University
1999
Stony Brook University
1995
Background— Clinical studies have demonstrated that 50% of individuals with chronic renal disease (CRD) die cardiovascular causes, including advanced calcific arterial and valvular disease; however, the mechanisms accelerated calcification in CRD remain obscure, no therapies can prevent progression. We recently vivo inflammation triggers calcification. In vitro evidence also indicates elastin degradation products may promote osteogenesis. Here, we used genetically modified mice molecular...
Pain and depression are frequently comorbid disorders, but the mechanism underlying this association is unknown. Here, we report that brain indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays key role comorbidity. We found chronic pain rats induced depressive behavior IDO1 upregulation bilateral hippocampus. Upregulation of resulted increased kynurenine/tryptophan ratio decreased serotonin/tryptophan observed elevated plasma IDO activity patients with...
Rasproteins can activate at least three classes of downstream target proteins: Raf kinases, phosphatidylinositol-3 phosphate (PI3) kinase, and Ral-specific guanine nucleotide exchange factors (Ral-GEFs).In NIH 3T3 cells, activated Ral-GEFs contribute to Ras-induced cell proliferation oncogenic transformation by complementing the activities PI3 kinases.In PC12 kinases mediate cycle arrest differentiation into a neuronal phenotype.Here, we show that in Ral-GEF activity acts opposite other Ras...
Recent increase in human lifespan has shifted the spectrum of aging-related disorders to an unprecedented upsurge cardiovascular diseases, especially calcific aortic valve stenosis, which 80% risk progression heart failure and death. A current therapeutic option for calcified valves is surgical replacement, provides only temporary relief. progress research suggested that arterial calcification are result active process osteogenic differentiation, induced by a pro-atherogenic inflammatory...
Ras proteins have the capacity to bind and activate at least three families of downstream target proteins: Raf kinases, phosphatidylinositol 3 (PI 3)-kinase, Ral-specific guanine nucleotide exchange factors (Ral-GEFs). We previously shown that Ras/Ral-GEF Ras/Raf pathways oppose each other upon nerve growth factor stimulation, with former promoting proliferation latter cell cycle arrest. Moreover, are not activated equally. While Ras/Raf/Erk signaling pathway is induced for hours,...
Abstract Notch receptors are key regulators of nervous system development and promoters neural stem cells renewal proliferation. Defects in the expression genes result severe, often lethal developmental abnormalities. Notch3 is generally thought to have a similar proliferative, anti‐differentiation gliogenic role Notch1. However, some cases, has an opposite, pro‐differentiation effect. Here, we show that segregates from Notch1 transiently expressed adult rat mouse spinal cord neuron...
Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI shown to induce spinal cord adult neurogenesis, which may contribute the increase in nociceptive sensitivity. Here, we show that also induces rapid and profound asymmetrical anatomical rearrangements rodent cerebellum pons. This remodelling occurs throughout hindbrain, addition regions involved pain processing, affects other sensory modalities. We...
Chronic pain is a debilitating condition with unknown mechanism. Nociceptive sensitivity may be regulated by genetic factors, some of which have been separately linked to neuronal progenitor cells and differentiation. This suggests that factors interfere differentiation contribute chronic increase in nociceptive sensitivity, extending the immature, hyperexcitable stage spinal cord neurons. Although adult rodent neurogenesis was previously demonstrated, fate these unknown. Here, we show...
Adult spinal cord neurogenesis occurs at low, constant rate under normal conditions and can be amplified by pathologic such as injury or disease. The immature neurons produced through adult have increased excitability migrate preferentially to the superficial dorsal horn layers responsible for nociceptive signaling. Under conditions, this process may maintaining a steady-state, but adaptable level of sensitivity, thus representing an experience-dependent mechanism regulation similar other...