A5009186877- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Tryptophan and brain disorders
- Dermatology and Skin Diseases
- Inflammasome and immune disorders
- Renal Transplantation Outcomes and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Transplantation: Methods and Outcomes
- Organ Transplantation Techniques and Outcomes
- RNA Interference and Gene Delivery
- Organ and Tissue Transplantation Research
- Calcium signaling and nucleotide metabolism
- Transgenic Plants and Applications
- Reproductive System and Pregnancy
- Adenosine and Purinergic Signaling
- Diabetes and associated disorders
- Asthma and respiratory diseases
- Neurogenesis and neuroplasticity mechanisms
- Telomeres, Telomerase, and Senescence
- Medicinal Plants and Bioactive Compounds
- Mast cells and histamine
- Diet and metabolism studies
- Skin Protection and Aging
Huntington Medical Research Institutes
2023-2024
Brigham and Women's Hospital
2013-2023
Harvard University
2013-2023
Mayo Clinic in Arizona
2018
Charité - Universitätsmedizin Berlin
2015
Innsbruck Medical University
2015
IFB Adiposity Diseases
2014
Children's Hospital
2009-2012
Boston Children's Hospital
2006-2011
Beth Israel Deaconess Medical Center
2010
Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses injury increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates aging augments immunogenicity. Ischemia reperfusion induces a systemic increase of cf-mt-DNA promotes dendritic cell-mediated, inflammatory responses. Comparable...
Neutrophil activation by infectious and inflammatory signals requires ATP release its feedback through purinergic receptors.
Wiskott-Aldrich syndrome protein (WASP) is in a complex with WASP-interacting (WIP). WASP levels, but not mRNA were severely diminished T cells from WIP(-/-) mice and increased by introduction of WIP these cells. The binding domain was shown to protect degradation calpain vitro. Treatment the proteasome inhibitors MG132 bortezomib levels B lymphocytes two WAS patients missense mutations (R86H T45M) that disrupt binding. inhibitor calpeptin activated patients, primary or mice. Despite its...
MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here, we describe a neuroprotective function of miR-132, the miRNA most significantly downregulated in neurons Alzheimer's disease. We demonstrate that miR-132 protects primary mouse human wild-type more vulnerable Tau-mutant against amyloid β-peptide (Aβ) glutamate excitotoxicity. It lowers levels total, phosphorylated, acetylated, cleaved forms Tau implicated...
CD4(+) T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD(+)) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model MS, by inducing immune homeostasis through CD4(+)IFNγ(+)IL-10(+) and reverses disease progression restoring tissue integrity via remyelination neuroregeneration. We NAD(+) regulates T-cell differentiation tryptophan hydroxylase-1 (Tph1), independently...
The cerebral cortex is essential for integration and processing of information that required most behaviors. exquisitely precise laminar organization the arises during embryonic development when neurons migrate successively from ventricular zones to coalesce into specific cortical layers. While radial glia act as guide rails projection neuron migration, pre-formed vascular networks provide support guidance cues GABAergic interneuron migration. This study provides novel conceptual mechanistic...
Atopic dermatitis (AD) skin lesions exhibit epidermal and dermal thickening, eosinophil infiltration, increased levels of the cysteinyl leukotriene (cys-LT) C 4 (LTC ). Epicutaneous sensitization with ovalbumin WT mice but not ΔdblGATA mice, latter which lack eosinophils, caused collagen deposition, mRNA expression cys-LT generating enzyme LTC synthase S). Skin thickening deposition were significantly reduced in ovalbumin-sensitized S-deficient type 2 receptor (CysLT R)–deficient 1...
Patients with atopic dermatitis (AD) often suffer from food allergy and develop flares upon skin contact allergens. However, it is unclear whether T cells sensitized to allergens in the gut promote this inflammation. To address question, we orally immunized WT mice lacking skin-homing chemokine receptor Ccr4 (Ccr4-/- mice) OVA then challenged them epicutaneously antigen. Allergic inflammation developed but not mutants was characterized by epidermal thickening, dermal infiltration eosinophils...
Abstract CD4 + CD25 Foxp3 Tregs have been shown to play a central role in immune homeostasis while preventing from fatal inflammatory responses, Th17 cells traditionally recognized as pro-inflammatory mediators implicated myriad of diseases. Studies the potential convert into and Tregs. Increasing evidence pointed out key molecule during this transdifferentiation process, however molecules that allow such development remain unknown. Here, we investigated impact NAD on fate in-depth,...
Sex-specific influences have been shown for a variety of diseases. Whether donor or recipient sex and hormone levels impact alloimmune responses remains unclear. In unifactorial multifactorial analyses more than 400 000 SRTR listed kidney transplant patients, we found that younger female recipients had an inferior death-censored graft survival was independent sex. contrast, superior in older recipients, suggesting the hormones over chromosomal mismatches. Those clinical changes were...
Eczema vaccinatum (EV) is a complication of smallpox vaccination occurring in patients with atopic dermatitis. In affected individuals, vaccinia virus (VV) spreads through the skin, resulting large primary lesions and satellite lesions, infects internal organs. BALB/c mice inoculated VV at sites Th2-biased allergic skin inflammation elicited by epicutaneous ovalbumin (OVA) sensitization exhibited larger that were erosive, more higher viral loads organs than saline-exposed unsensitized or...
Organ transplantation has seen an increased use of organs from older donors over the past decades in attempt to meet globally growing shortage donor organs. However, inferior outcomes when are used represent a challenge.
Ischemia-reperfusion injury (IRI) evokes intragraft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding mechanisms underlying these is fundamental to develop therapeutic regimens prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase mitochondrial damage and autophagy dendritic cells (DCs). While survival mechanism for ischemic DCs, it also augments their production of interleukin (IL)-6. Allograft-derived...