A5103274674- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Renal Transplantation Outcomes and Treatments
- Melanoma and MAPK Pathways
- Transplantation: Methods and Outcomes
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Organ Transplantation Techniques and Outcomes
- Protein Tyrosine Phosphatases
- Cancer Research and Treatments
- Protein Kinase Regulation and GTPase Signaling
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Wnt/β-catenin signaling in development and cancer
- Xenotransplantation and immune response
- Histone Deacetylase Inhibitors Research
- Cellular Mechanics and Interactions
- Viral gastroenteritis research and epidemiology
- Nasal Surgery and Airway Studies
- TGF-β signaling in diseases
- Cell death mechanisms and regulation
- NF-κB Signaling Pathways
- Liver physiology and pathology
Massachusetts General Hospital
2014-2025
Harvard University
2012-2025
Boston University
2025
Brigham and Women's Hospital
2023
Istituto Tecnico Industriale Alessandro Volta
2014
Harvard–MIT Division of Health Sciences and Technology
2003
Massachusetts Institute of Technology
2003
Tufts Medical Center
2003
Harvard University Press
1995-2001
National Cerebral and Cardiovascular Center
1999-2001
Mitogen-activated protein (MAP) kinases, also known as extracellular signal-regulated kinases (ERKs), are thought to act at an integration point for multiple biochemical signals because they activated by a wide variety of signals, rapidly phosphorylated on threonine and tyrosine, highly conserved. A critical kinase lies upstream MAP stimulates the enzymatic activity kinase. The structure this kinase, denoted MEK1, M AP or E RK k inase, was elucidated from complementary DNA sequence shown be...
The MEK1 ( M AP kinase/ E RK k inase)/ERK e xtracellular-signal- r esponsive inase) pathway has been implicated in cell growth and differentiation [Seger, R. & Krebs, E. G. (1995) FASEB J. 9, 726–735]. Here we show that the MEK/ERK is activated during focal cerebral ischemia may play a role inducing damage. Treatment of mice 30 min before with MEK1-specific inhibitor PD98059 [Alessi, D. R., Cuenda, A., Cohen, P., Dudley, T. Saltiel, A. Biol. Chem. 270, 27489–27494] reduces infarct volume...
Hypertrophy is a basic cellular response to variety of stressors and growth factors, has been best characterized in myocytes. Pathologic hypertrophy cardiac myocytes leads heart failure, major cause death disability the developed world. Several cytosolic signaling pathways have identified that transduce prohypertrophic signals, but date, little work focused on might negatively regulate hypertrophy. Herein, we report glycogen synthase kinase-3β (GSK-3β), protein kinase previously implicated...
Brain subjected to acute ischemic attack caused by an arterial blockage needs immediate recanalization. However, restoration of cerebral blood flow can cause tissue injury, which is termed reperfusion injury. It important inhibit injury achieve greater brain protection. Because oxidative stress has been shown activate mitogen-activated protein kinases (MAPKs), and because contributes MAPK may be a potential target after ischemia. Here, we demonstrate that forebrain ischemia dramatically...
Excessive release of glutamate and the subsequent influx calcium are associated with a number neurological insults that result in neuronal death. The calcium-activated intracellular signaling pathways responsible for this excitotoxic injury largely unknown. Here, we report PD098059, selective inhibitor p44/42 mitogen-activated protein kinase (MAP kinase) pathway, reduces death cell-culture model seizure activity. Dissociated hippocampal neurons grown chronically presence kynurenate, broad...
Chronic allograft vasculopathy (CAV) in murine heart allografts can be elicited by adoptive transfer of donor specific antibody (DSA) to class I MHC antigens and is independent complement. Here we address the mechanism which DSA causes CAV. B6.RAG1(-/-) or B6.RAG1(-/-)C3(-/-) (H-2(b)) mice received B10.BR (H-2(k)) repeated doses IgG2a, IgG1 F(ab')(2) fragments IgG2a (anti-H-2(k)). Intact regularly markedly stenotic CAV recipients over 28 days. In contrast, depletion NK cells with anti-NK1.1...
Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite multimodal therapy surgery and chemoradiation. Lenvatinib, a multi‐targeted tyrosine kinase inhibitor, as well checkpoint inhibitors targeting the programmed cell death pathway, proven effective in some patients advanced cancer. Combination of these therapies is potential means to boost effectiveness minimize treatment resistance ATC. We utilized our novel immunocompetent murine model orthotopic ATC...
Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite aggressive multimodal therapy. ATC has a high prevalence of BRAF
Long-term, immunosuppression-free allograft survival has been induced in human and nonhuman primate (NHP) kidney recipients after nonmyeloablative conditioning donor bone marrow transplantation (DBMT), resulting transient mixed hematopoietic chimerism. However, the same strategy consistently failed NHP heart transplant recipients. Here, we investigated whether long-term could be achieved by cotransplanting kidneys from donor. Cynomolgus monkeys were transplanted with allografts alone or...
The authors provide the first in vitro and vivo evidence that perturbations mitogen-activated protein kinase (MAPK) signal-transduction pathways are involved pathophysiology of traumatic brain injury. In primary rat cortical cultures, mechanical trauma induced a rapid selective phosphorylation extracellular signal-regulated (ERK) p38 kinase, whereas there was no detectable change c-jun N-terminal (JNK) pathway. Treatment with PD98059, which inhibits MAPK/ERK 1/2, upstream activator ERK,...
Oxidant stress and phospholipase A2 (PLA2) activation have been implicated in numerous proinflammatory responses of the mesangial cell (MC). We investigated cross-talk between group IVα cytosolic PLA2 (cPLA2α) secretory PLA2s (sPLA2s) during H2O2-induced arachidonic acid (AA) release using two types murine MC: (i) MC+/+, which lack IIa V PLA2s, (ii) MC–/–, groups IIa, V, PLA2s. AA was greater MC+/+ compared with MC–/–. It has argued that cPLA2α plays a regulatory role enhancing activity...
Recombinant Mek1 and Raf-1 proteins produced in Sf9 cells undergo a tight association both vivo vitro, which apparently does not depend on additional factors or the kinase activity of Raf-1. The complex can be disrupted by two polyclonal antibodies raised against peptides. Coinfection with activates > 150-fold, coinfection Erk1 approximately 90-fold. activation involves only serine phosphorylation, is directly proportional to extent activation. Phosphopeptide maps suggest single...
Bacterial expression of mouse gene Erk-1 yielded an active kinase with the same substrate specificity shown for ERK1 protein purified from rat cells. Although is believed to encode a serine/threonine based on sequence data and known phosphorylation sites, bacterially-produced (bt-Erk-1) autophosphorylated tyrosine in addition serine threonine residues. The bt-Erk-1 also had capacity reactivate ribosomal S6 (S6KII). Furthermore, treatment either serine/threonine-specific phosphatase 2A or...
The regulation of the Erk (extracellular-signal-regulated kinase) gene-encoded protein kinase activity by reversible phosphorylation has been reported to involve either an activator autophosphorylation or upstream kinase. In this communication we describe assays utilizing Erk-1 fused glutathione S-transferase that permit identification kinase(s) phosphorylate and activate myelin basic encoded gene. A phorbol ester-stimulated was identified phosphorylated a kinase-negative gene product on...
Although spontaneous kidney transplant acceptance/tolerance occurs in mice and occasionally humans, mechanisms remain unclear. Herein we test the hypothesis that EPO, a hormone predominantly produced by adult kidney, has immunomodulating properties are required for graft acceptance. In vitro , manner dependent on EPO receptor CD131 antigen-presenting cells, induced secretion of active TGF β which turn converted naïve CD4 + T cells into functional Foxp3 regulatory (Treg). murine models,...
Mouse kidney allografts are spontaneously accepted in select, fully mismatched donor-recipient strain combinations, like DBA/2J to C57BL/6 (B6), by natural tolerance. We previously showed renal grafts form aggregates containing various immune cells within 2 weeks posttransplant, referred as regulatory T cell–rich organized lymphoid structures, which a novel tertiary organ. To characterize the we performed single-cell RNA sequencing on CD45+ sorted from and rejected 1-week 6-months...