A5015950566- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Pituitary Gland Disorders and Treatments
- Immune cells in cancer
- CAR-T cell therapy research
- Stress Responses and Cortisol
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Cancer Immunotherapy and Biomarkers
- Adipokines, Inflammation, and Metabolic Diseases
- Monoclonal and Polyclonal Antibodies Research
- Intensive Care Unit Cognitive Disorders
- Adipose Tissue and Metabolism
- Long-Term Effects of COVID-19
- Regulation of Appetite and Obesity
- Cell death mechanisms and regulation
- Nutrition and Health in Aging
- Cancer, Stress, Anesthesia, and Immune Response
- Neonatal Respiratory Health Research
- Biosimilars and Bioanalytical Methods
- RNA regulation and disease
- Otolaryngology and Infectious Diseases
- S100 Proteins and Annexins
- COVID-19 Impact on Reproduction
- Meningioma and schwannoma management
Boston Children's Hospital
2022-2024
Harvard University
2023
Boston Medical Center
2022
Oregon Health & Science University
2015-2021
University of Colorado Denver
2011-2014
Veterans Health Administration
2012
University of Colorado Anschutz Medical Campus
2011
COVID-NET conducts population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in 99 counties † 14 states (California, Connecticut, Colorado, Georgia, Iowa, Maryland, Michigan, Minnesota, New Mexico, York, Ohio, Oregon, Tennessee, and Utah), representing all 10 U.S. Department of Health Human Services regions (2,3).Laboratory-confirmed COVID-19associated among residents a predefined catchment area who had positive SARS-CoV-2 molecular test during...
A priority in cancer research is to innovate therapies that are not only effective against tumor progression but also address comorbidities such as cachexia limit quality and quantity of life. We demonstrate TLR7/8 agonist R848 induces anti-tumor responses attenuates murine models pancreatic ductal adenocarcinoma (PDAC). In vivo, tumors from two three cell lines were R848-sensitive, resulting smaller mass, increased immune complexity, CD8+ T-cell infiltration activity, decreased Treg...
Introduction As SARS-CoV-2 has evolved, so its effects on the pediatric population.1 While early variants typically resulted in lower respiratory infections, recently identified Omicron variant may exhibit a predilection for upper airways.2 The relatively smaller tract children compared to adults been thought predispose them more severe clinical presentations resembling laryngotracheobronchitis, or croup. Caused by viral-induced subglottic airway inflammation, croup is classically...
Abstract Background Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) one of the most important conditions associated with cachexia, >80% PDAC patients suffering from condition. To establish cardinal features murine model PDAC‐associated we characterized effects implanting pancreatic tumour cell line syngeneic C57BL/6 KRAS G12D P53 R172H Pdx‐Cre +/+ (KPC) mouse. Methods Male female mice were inoculated...
Lipocalin 2 (LCN2) was recently identified as an endogenous ligand of the type 4 melanocortin receptor (MC4R), a critical regulator appetite. However, it remains unknown if this molecule influences appetite during cancer cachexia, devastating clinical entity characterized by decreased nutrition and progressive wasting. We demonstrate that LCN2 is robustly upregulated in murine models pancreatic cancer, its expression associated with reduced food consumption, Lcn2 deletion protective from...
Gonadotrope and null cell pituitary tumors cause significant morbidity, often presenting with signs of hypogonadism together visual disturbances due to mass effects. Surgery radiation are the only therapeutic options date. To identify dysregulated genes pathways that may play a role in tumorigenesis and/or progression, molecular profiling was performed on 14 gonadotrope tumors, nine normal human pituitaries obtained at autopsy serving as controls. Bioinformatic analysis identified putative...
Abstract Background Up to 80% of pancreatic cancer patients suffer from cachexia, a devastating condition that exacerbates underlying disease, reduces quality life, and increases treatment complications mortality. Tumour‐induced inflammation is linked this multifactorial wasting syndrome, but mechanisms effective treatments remain elusive. Myeloid differentiation factor (MyD88), key component the innate immune system, plays pivotal role in directing inflammatory response various insults. In...
Weight loss and anorexia are common symptoms in cancer patients that occur prior to initiation of therapy. Inflammation the brain is a driver these symptoms, yet cellular sources neuroinflammation during malignancy unknown. In mouse model pancreatic ductal adenocarcinoma (PDAC), we observed early robust myeloid cell infiltration into brain. Infiltrating immune cells were predominately neutrophils, which accumulated at unique central nervous system entry portal called velum interpositum,...
Lipocalin 2 (LCN2) is a pleiotropic molecule that induced in the central nervous system (CNS) several acute and chronic pathologies. The induction of LCN2 evolved as beneficial process, aimed at combating bacterial infection through sequestration iron from pathogens, while role during chronic, non-infectious disease remains unclear, recent studies suggest neurotoxic. However, whether sufficient to induce behavioral cognitive alterations unclear. In this paper, we sought address cerebral on...
Regulatory T cells (T regs ) make major contributions to immune homeostasis. Because reg dysfunction can lead both allo- and autoimmunity, there is interest in correcting these disorders through adoptive transfer. Two of the central challenges clinically deploying cellular therapies are ensuring phenotypic stability maximizing potency. Here, we describe an approach address issues creation OX40 ligand (OX40L)–specific chimeric antigen receptor (CAR)–T under control a synthetic forkhead box P3...
Toll-like receptors 7 and 8 (TLR7 TLR8) are endosomal pattern recognition that detect a variety of single-stranded RNA species. While TLR7/8 agonists have robust therapeutic potential, clinical utility these agents is limited by sickness responses associated with treatment induction. To understand the kinetics mechanism responses, we characterized acute chronic effects TLR7 stimulation. Single-cell RNA-sequencing studies, RNAscope, radiolabeled in situ hybridization demonstrate central...
Abstract Sickness behaviors and metabolic responses to invading pathogens are common nearly all types of infection. These evolved provide short-term benefit the host ward off infection, but impact on quality life when prolonged lead neurodegeneration, depression cachexia. Among major infectious agents, viruses most frequently enter brain, resulting in profound neuroinflammation. We sought define unique features inflammatory response brain these infections. demonstrate that molecular pathway...
Reprimo (RPRM), initially identified as a downstream effector of p53-induced cell cycle arrest at G2/M, is putative tumor suppressor silenced in some types cancer. In microarrays, the RPRM transcript was repressed 26-fold gonadotrope (null cell) human pituitary tumors compared with normal but absence changes p53. Inhibition mRNA confirmed by RT-PCR all tumors, most GH samples, and variably other types. Human showed no evidence abnormal promoter hypermethylation mechanism repression. stable...
Muscle atrophy occurs during chronic diseases, resulting in diminished quality of life and compromised treatment outcomes.There is a high demand for therapeutics that increase muscle mass while abrogating the need special dietary exercise requirements.Therefore, we developed an efficient nanomedicine approach capable increasing mass.Methods: The therapy based on nanoparticle-mediated delivery follistatin messenger RNA (mRNA) to liver after subcutaneous administration.The delivered mRNA...
Hypothalamic inflammation is a key component of acute sickness behavior and cachexia, yet mechanisms inflammatory signaling in the central nervous system remain unclear. Previous work from our lab others showed that while MyD88 an important pathway for behavior, knockout (MyD88KO) mice still experience after stimuli challenge. We found systemic lipopolysaccharide (LPS) challenge, MyD88KO elevated expression several cytokine chemokine genes hypothalamus. therefore assessed role additional...
Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Neonatal mice exposed hyperoxia develop a simplified lung structure that resembles BPD. Sustained activation transcription factor NF-κB and increased expression protective target genes attenuate hyperoxia-induced mortality in adults. However, effect enhancing activity on injury development neonatal animals is unknown. We performed this study determine whether sustained activation, mediated through IκBβ...
Microglia in the mediobasal hypothalamus (MBH) respond to inflammatory stimuli and metabolic perturbations mediate body composition. This concept is well studied context of high fat diet induced obesity (HFDO), yet has not been investigated cachexia, a devastating syndrome characterized by anorexia, fatigue, muscle catabolism. We show that microglia accumulate specifically MBH early pancreatic ductal adenocarcinoma (PDAC)-associated cachexia assume an activated morphology. Furthermore, we...
The transcription factor NF-κB regulates the cellular response to inflammatory and oxidant stress. Although many studies have evaluated activity following exposure oxidative stress, role of IκB family inhibitory proteins in modulating this remains unclear. Specifically, function IκBβ mediating stress has not been evaluated. We hypothesized that blocking stress-induced signaling through would prevent apoptotic cell death. Using knock-in mice (AKBI), which IκBα gene is replaced with cDNA, we...
Exposure to intrauterine inflammation impairs lung growth but paradoxically protects the neonatal pulmonary vasculature from hyperoxic injury. The mechanisms mediating these contradictory effects are unknown. objective is identify role of NF-κB in cytoprotective and proinflammatory responses fetal endothelium. In newborn rats exposed intra-amniotic LPS, we found increased expression target gene manganese superoxide dismutase (MnSOD) Supporting vivo findings, LPS induced activation MnSOD...
Supplemental oxygen is frequently used in an attempt to improve delivery; however, prolonged exposure results damage the pulmonary endothelium and epithelium. Although NF-κB has been identified as a redox-responsive transcription factor, whether activation exacerbates or attenuates hyperoxic lung injury unclear. We determined that sustained activity mediated by IκBβ prevents mortality adult mice exposed greater than 95% O2. Adult wild-type demonstrated evidence of alveolar protein leak 100%...
Abstract Weight loss, fatigue, and cognitive dysfunction are common symptoms in cancer patients that occur prior to initiation of therapy. Inflammation the brain is a driver these symptoms, yet cellular sources neuroinflammation during malignancy unknown. In mouse model pancreatic ductal adenocarcinoma (PDAC), we observed early robust myeloid cell infiltration into brain. Infiltrating immune cells were predominately neutrophils, which accumulated at unique central nervous system entry portal...