A5066552417- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- Pregnancy and preeclampsia studies
- Birth, Development, and Health
- Gestational Diabetes Research and Management
- Spinal Dysraphism and Malformations
- Fetal and Pediatric Neurological Disorders
- Cytomegalovirus and herpesvirus research
- Toxoplasma gondii Research Studies
- Reproductive Biology and Fertility
- Peroxisome Proliferator-Activated Receptors
- CAR-T cell therapy research
- Lipid metabolism and disorders
- Neurogenesis and neuroplasticity mechanisms
- Reproductive Physiology in Livestock
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Cerebrospinal fluid and hydrocephalus
- FOXO transcription factor regulation
- Neonatal Respiratory Health Research
- Herpesvirus Infections and Treatments
- Spinal Cord Injury Research
- interferon and immune responses
- Anesthesia and Neurotoxicity Research
Cincinnati Children's Hospital Medical Center
2015-2025
Children's Hospital & Medical Center
2020-2022
University of Cincinnati Medical Center
2009-2020
University of Cincinnati
2020
Hospital Research Foundation
2012
Oncology Hematology Care
2012
Nonalcoholic fatty liver disease (NAFLD), a metabolic predisposition for development of hepatocellular carcinoma (HCC), represents spectrum ranging from steatosis to steatohepatitis cirrhosis. Acox1, rate-limiting enzyme in peroxisomal acid β-oxidation, regulates metabolism, spontaneous hepatic steatosis, and damage over time. However, it is unknown whether Acox1 modulates inflammation relevant NAFLD pathogenesis or if Acox1-associated inflammatory derangements uncover accelerate potential...
NK cells require Gab3 for peripheral expansion, tumor eradication, and resistance to trophoblast invasion during pregnancy. See the related Focus by Colucci .
Developing novel strategies to overcome the immunosuppressive tumor microenvironment is a critically important area of cancer therapy research. Here, we assess therapeutic potential CD244 (2B4/signaling lymphocyte activation molecule family 4), an immunoregulatory receptor found on variety immune cells, including exhausted CD8
Congenital hydrocephalus (HCP) is a prevalent condition, that leads to fetal cerebral ventricle dilation and increased intracranial pressure. It associated with significant neurological impairments, partly due the disruption of neurogenesis gliogenesis. This study aims investigate alterations in proliferation differentiation neural progenitor cells (NPCs) lamb model obstructive HCP induced by intracisternal BioGlue injection, identify potential optimal intervention time for prenatal surgery....
Homeostatic control of the immune system involves mechanisms that ensure self-tolerance, survival and quiescence hematopoietic-derived cells. In this study, we demonstrate GTPase immunity associated protein (Gimap)5 regulates these processes in lymphocytes hematopoietic progenitor As a consequence recessive N-ethyl-N-nitrosourea-induced germline mutation P-loop Gimap5, lymphopenia, hepatic extramedullary hematopoiesis, weight loss, intestinal inflammation occur homozygous mutant mice....
Fetal growth restriction (FGR) significantly contributes to neonatal and perinatal morbidity mortality. Currently, there are no effective treatment options for FGR during pregnancy. We have developed a nanoparticle gene therapy targeting the placenta increase expression of human insulin-like factor 1 (hIGF1) correct fetal trajectories. Using maternal nutrient guinea pig model FGR, an ultrasound-guided, intraplacental injection nonviral, polymer-based hIGF1 containing plasmid with...
Abstract GTPase of immunity-associated protein 5 (Gimap5) is linked with lymphocyte survival, autoimmunity, and colitis, but its mechanisms action are unclear. Here, we show that Gimap5 essential for the inactivation glycogen synthase kinase-3β (GSK3β) following T cell activation. In absence Gimap5, constitutive GSK3β activity constrains c-Myc induction NFATc1 nuclear import, thereby limiting productive CD4 + proliferation. Additionally, facilitates Ser389 phosphorylation translocation...
Currently, there is no effective treatment for placental dysfunction in utero. In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 factor (
Abstract Previously, we reported the abrogation of quiescence and reduced survival in lymphocytes from Gimap5sph/sph mice, an ENU germline mutant with a missense mutation GTPase immunity-associated protein 5 (Gimap5). These mice showed progressive loss peripheral lymphocyte populations developed spontaneous colitis, resulting early mortality. In this study, identify molecular pathways that contribute to onset colitis mice. We show CD4+ T cells become Th1/Th17 polarized are critically...
During embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times locations within the cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a role neuronal dysfunction associated with this condition. However, to date, pathophysiological mechanisms related astrocytic response bifida are poorly understood. This study aimed characterize development...
Rhodamine 123 and epifluorescence microscopy revealed a significant portion of the fat cell's mitochondria existed in form clusters or aggregates, whereas remainder were scattered about cytoplasm. The aggregates variable size number apparently bore no fixed relationship to nucleus each other. Mitochondrial seen vivo rat mouse adipocytes mesenteric epididymal depots, excised tissue pieces other isolated cells. Physiological factors investigated such as species type (rat, mouse, rabbit, dog),...
Using a small scale ENU mutagenesis approach we identified recessive germline mutant, designated Lampe1 that exhibited growth retardation and spontaneous hepatosteatosis. Low resolution mapping based on 20 intercrossed mice revealed linkage to ∼14 Mb interval the distal site of chromosome 11 containing total 285 genes. Exons 50 bp flanking sequences within critical region were enriched with sequence capture microarrays subsequently analyzed by next-generation sequencing. this 98.1 percent...
Abstract Myriad studies have linked type I IFN to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). Although increased levels are found in patients with SLE, and blockade ameliorates disease many mouse models lupus, its precise roles driving SLE remain largely unknown. In this study, we dissected effect sensing by CD4 T cells B on development follicular helper (TFH), germinal center (GC) cells, plasmablasts, antinuclear dsDNA IgG using bm12 chronic...
Programmed death-1 (PD-1) plays an important role in mediating immune tolerance through mechanisms that remain unclear. Herein, we investigated whether PD-1 prevents excessive host tissue damage during infection with the protozoan parasite, Toxoplasma gondii. Surprisingly, our results demonstrate PD-1-deficient mice have increased susceptibility to T. gondii, parasite cyst counts along reduced type-1 cytokine responses (IL-12 and IFN-γ). PD-1⁻/⁻ DCs showed no cell intrinsic defect IL-12...
Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety target cells, yet the pathways underlying “missing‐self” recognition, including involvement activating receptors, remain poorly understood. Using ethyl‐ N ‐nitrosourea mutagenesis in mice, we identified germline mutant, designated Ace , with marked defect cell mediated recognition and elimination targets. The causative mutation was linked to chromosome 11 as missense (Thr428Ile) SH2 domain...
Myelomeningocele (MMC) is a congenital birth defect of the spine and spinal cord, commonly treated clinically through prenatal or postnatal surgery by repairing unclosed canal. Having previously developed PLA/PCL polymer smart patch for this condition, we aim to further expand potential therapeutic options providing additional cellular biochemical support in addition its mechanical properties. Bone morphogenetic proteins (BMPs) are large class secreted factors that serve as modulators...
The immune system exerts a critical function as it recognizes and eliminates transformed or neoplastic cells, process also referred to immunosurveillance. NK cells play particularly important role in that they are able recognize tumor via "missing-self"-i.e., the absence of major histocompatibility complex Class I on target cells. Moreover, recent studies suggest participate onset regulation adaptive responses. exact molecular pathways by which this occurs, however, remain poorly understood....
One of the greatest challenges to development and implementation pregnancy therapeutics is ability rigorously test treatments in clinically relevant animal models. Guinea pigs offer a unique advantage studying placenta, fetal development, reproductive health as they have similar developmental milestones humans, both throughout gestation following birth. Tracking guinea pig estrus cycle imperative ensuring appropriately timed mating can be performed by monitoring vaginal membrane. Here, we...
Abstract Currently, there is no effective treatment for placenta dysfunction in utero . In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 factor ( hIGF1 ) gene delivery (NP-Plac1-hIGF1) increased expression and maintained growth. However, whether it can restore remains to be determined. Using the endothelial nitric oxide synthase knockout (eNOS −/− model, genetic FGR, we found that despite inducing placentas treated with NP-Plac1-hIGF1...