michelle hernandez - Academia.edu (original) (raw)

Papers by michelle hernandez

Biomedicines

In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired... more In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired cardiac function, pathological remodeling, chronic inflammation, endothelial dysfunction, neurohormonal activation, and altered nitric oxide-related pathways. Pre-clinical HFrEF studies have shown that treatment with sodium–glucose cotransporter-2 inhibitors (SGLT-2i) stimulates natriuretic and osmotic/diuretic effects, improves overall cardiac function, attenuates maladaptive cardiac remodeling, and reduces chronic inflammation, oxidative stress, and endothelial dysfunction. Here, we review the mechanisms and effects of SGLT-2i therapy on cardiogenic edema in various models of HFrEF. Overall, the data presented suggest a high translational importance of these studies, and pre-clinical studies show that SGLT-2i therapy has a marked effect on suppressing the progression of HFrEF through multiple mechanisms, including those that affect the development of cardiogenic edema.

2020 IEEE SENSORS, 2020

Multi-modal wearable sensors monitoring physiology and environment simultaneously would offer a g... more Multi-modal wearable sensors monitoring physiology and environment simultaneously would offer a great promise to manage respiratory health, especially for asthmatic patients. In this study, we present a preliminary investigation of the correlation between ozone exposure, heart rate, heart rate variability, and lung function. As the first step, we tested the effect of low-level ozone exposure in a sample size of four healthy individuals. Test subjects underwent controlled exposure from 0.06 to 0.08 ppm of ozone and filtered air on two separate exposure days. Our results indicate an increment in mean heart rate in three out of four test subjects when exposed to ozone. We have also observed that changes in mean heart rate has a positive correlation with changes in lung function and a negative correlation with changes in neutrophil count. These results provide a baseline understanding of healthy subjects as a control group.

Journal of Allergy and Clinical Immunology, 2021

ERJ Open Research, 2021

BackgroundImpaired mucus clearance and airway mucus plugging have been shown to occur in moderate... more BackgroundImpaired mucus clearance and airway mucus plugging have been shown to occur in moderate–severe asthma, especially during acute exacerbations. In cystic fibrosis, where airway mucus is dehydrated, it has been shown that inhaled hypertonic saline (HS) produces both acute and sustained enhancement of mucociliary clearance (MCC). The current study was designed to assess the acute and sustained effect of inhaled 7% HS on MCC in adult asthma.MethodsWell-controlled, moderate–severe female asthmatic patients (n=8) were screened with a single test dose of albuterol (four puffs by metered-dose inhaler) followed by HS (7% sodium chloride, 4 mL using PARI LC Star nebuliser). Spirometry was measured pre-treatment and 5 and 30 min post-treatment for safety. MCC was measured using γ-scintigraphy on three separate visits: at baseline, during inhalation and 4 h after a single dose of HS.ResultsMCC was acutely enhanced during HS treatment; mean±sd clearance over 60 min of dynamic imaging (A...

Journal of Allergy and Clinical Immunology, 2021

Critical Care Medicine, 2020

INTRODUCTION: Spontaneous pneumothorax is a complication seen in patients with SARS-CoV-2 on mech... more INTRODUCTION: Spontaneous pneumothorax is a complication seen in patients with SARS-CoV-2 on mechanical ventilation, particularly in those who develop ARDS We report a case with spontaneous pneumothorax as the initial presentation of SARS-CoV-2 METHODS: A 56-year-old diabetic male presented in the midst of the SARS-CoV-2 outbreak in Queens, New York with a chief complaint of shortness of breath for four weeks His home medications included insulin glargine and metformin Upon presentation, the patient was found to have blood oxygen saturation of 61% on room air Subsequent radiographic imaging revealed bilateral pneumothoraces, extensive pneumomediastinum with air extending into the soft tissues of the lower neck, and extensive bilateral airspace opacities The patient was placed on a non-rebreather mask with significant improvement in blood oxygen saturation Initially, a right sided 14-french chest tube was inserted with reduction in the size of the pneumothorax, but due to worsening left-sided disease, the patient required placement of an additional left sided chest tube ten days into hospitalization The patient remained clinically stable on oxygen therapy via a non-rebreather mask;thus intubation was deferred On hospital day 22 and 23, the chest tubes were sequentially removed after the pneumothoraces resolved and the patient's supplemental oxygen requirement decreased He remained stable and was discharged with appropriate follow up RESULTS: To date, the data for non-mechanically ventilated patients with SARS-CoV-2 infection presenting with spontaneous pneumothorax remains limited Previous case studies include those of Sun R et al and N Chen et al, each highlighting one case of spontaneous pneumothorax occurring in China Currently, there are no published cases of spontaneous pneumothorax in non-mechanically ventilated patients in the United States The pathophysiology of development of spontaneous pneumothorax in SARSCoV- 2 patients is not fully understood, however histological examination of affected lungs show diffuse alveolar damage and mucinous exudate, similar to that of acute respiratory distress syndrome It is imperative to recognize that pneumothorax may be a potential complication of SARS-CoV-2 pneumonia, especially due to the high global incidence of SARS-CoV-2

Cell Reports, 2020

AUTHOR CONTRIBUTIONS M.M.-F. and C.G. designed and performed most of the experiments, analyzed th... more AUTHOR CONTRIBUTIONS M.M.-F. and C.G. designed and performed most of the experiments, analyzed the data, and wrote the manuscript. M.B.G.-M. and S.M.L. carried out the clinical management and analysis of P4 and edited the manuscript.

Perspectives of the ASHA Special Interest Groups, 2017

The true power of otoacoustic emissions (OAEs) continues to be explored. OAE spectral characteris... more The true power of otoacoustic emissions (OAEs) continues to be explored. OAE spectral characteristics are typically studied in research and applied in the clinic. However, OAE temporal aspects are relatively underexplored. Not using temporal features is similar to ignoring nearly half of the information that OAEs provide. Besides providing information related to the generation of OAEs and cochlear mechanics, the temporal characteristics have important clinical implications, such as for assessing frequency selectivity, characterizing the strength of the efferent auditory system. This review provides a general synopsis of the fundamental principles of OAE delay and latency and discusses some of the relevant applications in probing the strength of the efferent neural pathway and frequency selectivity. It is expected that the reader will gain an overview of the implications of the latency or phase behavior of OAEs.

In vitro cellular & developmental biology. Animal, Jan 29, 2018

The diversity and extent of signaling functions of nitric oxide (NO) in cell physiology as well a... more The diversity and extent of signaling functions of nitric oxide (NO) in cell physiology as well as its presence and influence as a common component of ambient air pollution and tobacco smoke are gaining increasing research attention relative to both health and disease. While cellular NO production is typically associated with inflammatory cells and processes, the airway epithelium particularly of the paranasal sinuses, has been documented to be a rich source of excreted NO. Inasmuch as excreted NO derives from both mucosal and inflammatory cell sources, distinguishing the individual contribution of these compartments to total excreted cellular NO is potentially problematic. We simulated an inflammatory mucosal environment by stimulating human nasal epithelial cultures with interleukin-13 (IL-13), a mediator produced by eosinophils in asthma, allergic rhinitis, and sinusitis. While a consistent baseline of NO excretion in control cultures was documented, widely variable individual re...

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 17, 2017

Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rod... more Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rodent studies indicate that AgNPs can cause lung inflammation and toxicity in a strain- and particle type-dependent manner, but mechanisms of susceptibility remain unclear. The aim of this study was to assess the variation in AgNP-induced lung inflammation and toxicity across multiple inbred mouse strains and to use genome-wide association (GWA) mapping to identify potential candidate susceptibility genes. Mice received doses of 0.25 mg/kg of either 20-nm citrate-coated AgNPs or citrate buffer using oropharyngeal aspiration. Neutrophils in bronchoalveolar lavage fluid (BALF) served as markers of inflammation. We found significant strain- and treatment-dependent variation in neutrophils in BALF. GWA mapping identified 10 significant single-nucleotide polymorphisms (false discovery rate, 15%) in 4 quantitative trait loci on mouse chromosomes 1, 4, 15, and 18, and Nedd4l (neural precursor cel...

Journal of Toxicology and Environmental Health, Part A, 2015

Particulate matter (PM) exposures have been linked to mortality, low birth weights, hospital admi... more Particulate matter (PM) exposures have been linked to mortality, low birth weights, hospital admissions, and diseases associated with metabolic syndrome, including diabetes mellitus, cardiovascular disease, and obesity. In a previous in vitro and in vivo study, data demonstrated that PM 10µm collected from Jeddah, Saudi Arabia (PM SA) altered expression of genes involved in lipid and cholesterol metabolism, as well as many other genes associated with metabolic disorders. PM SA contains a relatively high concentration of nickel (Ni), known to be linked to several metabolic disorders. In order to evaluate if Ni and PM exposures induce similar gene expression profiles, mice were exposed to 100µg/50µl PM SA (PM-100), 50µg/50µl nickel chloride (Ni-50), or 100µg/50µl nickel chloride (Ni-100) twice a week for 4 weeks and hepatic gene expression changes determined. Ultimately, 55 of the same genes were altered in all 3 exposures. However, where the two Ni groups differed markedly was in the regulation (up or down) of these genes. Ni-100 and PM-100 groups displayed similar regulations, whereby 104 of the 107 genes were similarly modulated. Many of the 107 genes involved in metabolic syndrome and include ALDH4A1, BCO2, CYP1A, CYP2U, TOP2A. In addition, the top affected pathways such as fatty acid α-oxidation, and lipid and carbohydrate metabolism, are involved in metabolic diseases. Most notably, the top diseased outcome affected by these changes in gene expression was cardiovascular disease. Given these data, it appears that Ni and PM SA exposures display similar gene expression profiles, modulating the expression of genes involved in metabolic disorders.

BMC Genomics, 2015

Background: Otitis media is the most common disease of childhood, and represents an important hea... more Background: Otitis media is the most common disease of childhood, and represents an important health challenge to the 10-15% of children who experience chronic/recurrent middle ear infections. The middle ear undergoes extensive modifications during otitis media, potentially involving changes in the expression of many genes. Expression profiling offers an opportunity to discover novel genes and pathways involved in this common childhood disease. The middle ears of 320 WBxB6 F1 hybrid mice were inoculated with non-typeable Haemophilus influenzae (NTHi) or PBS (sham control). Two independent samples were generated for each time point and condition, from initiation of infection to resolution. RNA was profiled on Affymetrix mouse 430 2.0 whole-genome microarrays. Results: Approximately 8% of the sampled transcripts defined the signature of acute NTHi-induced otitis media across time. Hierarchical clustering of signal intensities revealed several temporal gene clusters. Network and pathway enrichment analysis of these clusters identified sets of genes involved in activation of the innate immune response, negative regulation of immune response, changes in epithelial and stromal cell markers, and the recruitment/function of neutrophils and macrophages. We also identified key transcriptional regulators related to events in otitis media, which likely determine the expression of these gene clusters. A list of otitis media susceptibility genes, derived from genome-wide association and candidate gene studies, was significantly enriched during the early induction phase and the middle re-modeling phase of otitis but not in the resolution phase. Our results further indicate that positive versus negative regulation of inflammatory processes occur with highly similar kinetics during otitis media, underscoring the importance of anti-inflammatory responses in controlling pathogenesis. Conclusions: The results characterize the global gene response during otitis media and identify key signaling and transcription factor networks that control the defense of the middle ear against infection. These networks deserve further attention, as dysregulated immune defense and inflammatory responses may contribute to recurrent or chronic otitis in children.

Annals of Allergy, Asthma & Immunology, 2015

African Americans disproportionally experience uncontrolled asthma 1. Because asthma control is n... more African Americans disproportionally experience uncontrolled asthma 1. Because asthma control is now the focus of asthma management, 2 publicly available questionnaires like the Asthma Control Test ™ (ACT) 3 and childhood Asthma Control Test (ACTc) 4 represent the

Innate immunity, 2012

Otitis media (OM), a common infectious disease in children, is associated with bacterial middle e... more Otitis media (OM), a common infectious disease in children, is associated with bacterial middle ear (ME) infection. Toll-like receptors (TLRs) are important mediators of innate immune responses, and TLR9 specifically recognizes the unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacterial DNA. Additional sensors of foreign DNA have recently been identified. The role of DNA sensing and TLR9 was investigated in a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). Expression of genes related to DNA-sensing pathways involved in innate immunity was assessed via DNA microarray, qPCR and immunohistochemistry. Middle ear responses to NTHi were examined in wild-type and TLR9(-/-) mice by histopathology and bacterial culture. Expression of TLR9 signaling genes was modestly up-regulated during OM, as was TLR9 protein in both ME mucosal cells and infiltrating leukocytes. However, genes known to be regulated by CpG DNA were dramatically up-regulated, as were gene...

Current Allergy and Asthma Reports, 2006

Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of human immunity and... more Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of human immunity and hypersensitivity. New discoveries in common variable immunodeficiency, the most enigmatic of PID syndromes, reveal molecular pathways of importance in human antibody production. FOXP3 mutations demonstrate the essential role that T-regulatory cells play in controlling autoantibody formation and disease. Interleukin-1 receptor-associated kinase 4 deficiency emphasizes the key role that innate immunity plays in the defense of bacterial disease occurring early in life. With respect to therapy, subcutaneous immunoglobulin treatment may indeed be a better treatment than intravenous immunoglobulin for many patients with antibody deficiency. Finally, PIDs remain in the vanguard for the treatment of inherited disorders by gene therapy. Gene therapy has cured patients with chronic granulomatous disease and severe combined immunodeficiency, but not without morbidity and mortality. Into the 21st century, PIDs continue to instruct us in human health and disease.

Pediatric Transplantation, 2009

OS is an inherited disorder characterized by immunodeficiency, diffuse erythroderma, hepatospleno... more OS is an inherited disorder characterized by immunodeficiency, diffuse erythroderma, hepatosplenomegaly, lymphadenopathy, protracted diarrhea, and failure to thrive. It was first described by Gilbert S. Omenn in 1965 (1). The report centered on an inbred Irish Catholic family whose family history was significant for 12 infants that died with similar clinical features. The propositus of the report presented at 33 days of age with a generalized erythematous papular and vesicular skin eruption, chronic diarrhea, hepatomegaly, conjunctivitis, and mild fevers, with laboratory findings significant for eosinophilia. During the course of the infantÕs hospital stay, he developed multiple infections and eventually died of respiratory and cardiac failure. Autopsy demonstrated pneumonitis secondary to Pneumocystis carinii, bilateral otitis media and inflammatory infiltrates in the lymph nodes, skin, liver, and spleen. Pedigree analysis of the family demonstrated the syndrome to be inherited in an autosomal recessive manner. Since that initial report, inherited mutations in either of the recombination activating genes RAG1 or RAG2, resulting in partial V(D)J recombinase activity, have been shown to be responsible for many cases of OS, although there is significant clinical and genetic heterogeneity

Biomedicines

In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired... more In heart failure with reduced ejection fraction (HFrEF), cardiogenic edema develops from impaired cardiac function, pathological remodeling, chronic inflammation, endothelial dysfunction, neurohormonal activation, and altered nitric oxide-related pathways. Pre-clinical HFrEF studies have shown that treatment with sodium–glucose cotransporter-2 inhibitors (SGLT-2i) stimulates natriuretic and osmotic/diuretic effects, improves overall cardiac function, attenuates maladaptive cardiac remodeling, and reduces chronic inflammation, oxidative stress, and endothelial dysfunction. Here, we review the mechanisms and effects of SGLT-2i therapy on cardiogenic edema in various models of HFrEF. Overall, the data presented suggest a high translational importance of these studies, and pre-clinical studies show that SGLT-2i therapy has a marked effect on suppressing the progression of HFrEF through multiple mechanisms, including those that affect the development of cardiogenic edema.

2020 IEEE SENSORS, 2020

Multi-modal wearable sensors monitoring physiology and environment simultaneously would offer a g... more Multi-modal wearable sensors monitoring physiology and environment simultaneously would offer a great promise to manage respiratory health, especially for asthmatic patients. In this study, we present a preliminary investigation of the correlation between ozone exposure, heart rate, heart rate variability, and lung function. As the first step, we tested the effect of low-level ozone exposure in a sample size of four healthy individuals. Test subjects underwent controlled exposure from 0.06 to 0.08 ppm of ozone and filtered air on two separate exposure days. Our results indicate an increment in mean heart rate in three out of four test subjects when exposed to ozone. We have also observed that changes in mean heart rate has a positive correlation with changes in lung function and a negative correlation with changes in neutrophil count. These results provide a baseline understanding of healthy subjects as a control group.

Journal of Allergy and Clinical Immunology, 2021

ERJ Open Research, 2021

BackgroundImpaired mucus clearance and airway mucus plugging have been shown to occur in moderate... more BackgroundImpaired mucus clearance and airway mucus plugging have been shown to occur in moderate–severe asthma, especially during acute exacerbations. In cystic fibrosis, where airway mucus is dehydrated, it has been shown that inhaled hypertonic saline (HS) produces both acute and sustained enhancement of mucociliary clearance (MCC). The current study was designed to assess the acute and sustained effect of inhaled 7% HS on MCC in adult asthma.MethodsWell-controlled, moderate–severe female asthmatic patients (n=8) were screened with a single test dose of albuterol (four puffs by metered-dose inhaler) followed by HS (7% sodium chloride, 4 mL using PARI LC Star nebuliser). Spirometry was measured pre-treatment and 5 and 30 min post-treatment for safety. MCC was measured using γ-scintigraphy on three separate visits: at baseline, during inhalation and 4 h after a single dose of HS.ResultsMCC was acutely enhanced during HS treatment; mean±sd clearance over 60 min of dynamic imaging (A...

Journal of Allergy and Clinical Immunology, 2021

Critical Care Medicine, 2020

INTRODUCTION: Spontaneous pneumothorax is a complication seen in patients with SARS-CoV-2 on mech... more INTRODUCTION: Spontaneous pneumothorax is a complication seen in patients with SARS-CoV-2 on mechanical ventilation, particularly in those who develop ARDS We report a case with spontaneous pneumothorax as the initial presentation of SARS-CoV-2 METHODS: A 56-year-old diabetic male presented in the midst of the SARS-CoV-2 outbreak in Queens, New York with a chief complaint of shortness of breath for four weeks His home medications included insulin glargine and metformin Upon presentation, the patient was found to have blood oxygen saturation of 61% on room air Subsequent radiographic imaging revealed bilateral pneumothoraces, extensive pneumomediastinum with air extending into the soft tissues of the lower neck, and extensive bilateral airspace opacities The patient was placed on a non-rebreather mask with significant improvement in blood oxygen saturation Initially, a right sided 14-french chest tube was inserted with reduction in the size of the pneumothorax, but due to worsening left-sided disease, the patient required placement of an additional left sided chest tube ten days into hospitalization The patient remained clinically stable on oxygen therapy via a non-rebreather mask;thus intubation was deferred On hospital day 22 and 23, the chest tubes were sequentially removed after the pneumothoraces resolved and the patient's supplemental oxygen requirement decreased He remained stable and was discharged with appropriate follow up RESULTS: To date, the data for non-mechanically ventilated patients with SARS-CoV-2 infection presenting with spontaneous pneumothorax remains limited Previous case studies include those of Sun R et al and N Chen et al, each highlighting one case of spontaneous pneumothorax occurring in China Currently, there are no published cases of spontaneous pneumothorax in non-mechanically ventilated patients in the United States The pathophysiology of development of spontaneous pneumothorax in SARSCoV- 2 patients is not fully understood, however histological examination of affected lungs show diffuse alveolar damage and mucinous exudate, similar to that of acute respiratory distress syndrome It is imperative to recognize that pneumothorax may be a potential complication of SARS-CoV-2 pneumonia, especially due to the high global incidence of SARS-CoV-2

Cell Reports, 2020

AUTHOR CONTRIBUTIONS M.M.-F. and C.G. designed and performed most of the experiments, analyzed th... more AUTHOR CONTRIBUTIONS M.M.-F. and C.G. designed and performed most of the experiments, analyzed the data, and wrote the manuscript. M.B.G.-M. and S.M.L. carried out the clinical management and analysis of P4 and edited the manuscript.

Perspectives of the ASHA Special Interest Groups, 2017

The true power of otoacoustic emissions (OAEs) continues to be explored. OAE spectral characteris... more The true power of otoacoustic emissions (OAEs) continues to be explored. OAE spectral characteristics are typically studied in research and applied in the clinic. However, OAE temporal aspects are relatively underexplored. Not using temporal features is similar to ignoring nearly half of the information that OAEs provide. Besides providing information related to the generation of OAEs and cochlear mechanics, the temporal characteristics have important clinical implications, such as for assessing frequency selectivity, characterizing the strength of the efferent auditory system. This review provides a general synopsis of the fundamental principles of OAE delay and latency and discusses some of the relevant applications in probing the strength of the efferent neural pathway and frequency selectivity. It is expected that the reader will gain an overview of the implications of the latency or phase behavior of OAEs.

In vitro cellular & developmental biology. Animal, Jan 29, 2018

The diversity and extent of signaling functions of nitric oxide (NO) in cell physiology as well a... more The diversity and extent of signaling functions of nitric oxide (NO) in cell physiology as well as its presence and influence as a common component of ambient air pollution and tobacco smoke are gaining increasing research attention relative to both health and disease. While cellular NO production is typically associated with inflammatory cells and processes, the airway epithelium particularly of the paranasal sinuses, has been documented to be a rich source of excreted NO. Inasmuch as excreted NO derives from both mucosal and inflammatory cell sources, distinguishing the individual contribution of these compartments to total excreted cellular NO is potentially problematic. We simulated an inflammatory mucosal environment by stimulating human nasal epithelial cultures with interleukin-13 (IL-13), a mediator produced by eosinophils in asthma, allergic rhinitis, and sinusitis. While a consistent baseline of NO excretion in control cultures was documented, widely variable individual re...

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 17, 2017

Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rod... more Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, in vivo rodent studies indicate that AgNPs can cause lung inflammation and toxicity in a strain- and particle type-dependent manner, but mechanisms of susceptibility remain unclear. The aim of this study was to assess the variation in AgNP-induced lung inflammation and toxicity across multiple inbred mouse strains and to use genome-wide association (GWA) mapping to identify potential candidate susceptibility genes. Mice received doses of 0.25 mg/kg of either 20-nm citrate-coated AgNPs or citrate buffer using oropharyngeal aspiration. Neutrophils in bronchoalveolar lavage fluid (BALF) served as markers of inflammation. We found significant strain- and treatment-dependent variation in neutrophils in BALF. GWA mapping identified 10 significant single-nucleotide polymorphisms (false discovery rate, 15%) in 4 quantitative trait loci on mouse chromosomes 1, 4, 15, and 18, and Nedd4l (neural precursor cel...

Journal of Toxicology and Environmental Health, Part A, 2015

Particulate matter (PM) exposures have been linked to mortality, low birth weights, hospital admi... more Particulate matter (PM) exposures have been linked to mortality, low birth weights, hospital admissions, and diseases associated with metabolic syndrome, including diabetes mellitus, cardiovascular disease, and obesity. In a previous in vitro and in vivo study, data demonstrated that PM 10µm collected from Jeddah, Saudi Arabia (PM SA) altered expression of genes involved in lipid and cholesterol metabolism, as well as many other genes associated with metabolic disorders. PM SA contains a relatively high concentration of nickel (Ni), known to be linked to several metabolic disorders. In order to evaluate if Ni and PM exposures induce similar gene expression profiles, mice were exposed to 100µg/50µl PM SA (PM-100), 50µg/50µl nickel chloride (Ni-50), or 100µg/50µl nickel chloride (Ni-100) twice a week for 4 weeks and hepatic gene expression changes determined. Ultimately, 55 of the same genes were altered in all 3 exposures. However, where the two Ni groups differed markedly was in the regulation (up or down) of these genes. Ni-100 and PM-100 groups displayed similar regulations, whereby 104 of the 107 genes were similarly modulated. Many of the 107 genes involved in metabolic syndrome and include ALDH4A1, BCO2, CYP1A, CYP2U, TOP2A. In addition, the top affected pathways such as fatty acid α-oxidation, and lipid and carbohydrate metabolism, are involved in metabolic diseases. Most notably, the top diseased outcome affected by these changes in gene expression was cardiovascular disease. Given these data, it appears that Ni and PM SA exposures display similar gene expression profiles, modulating the expression of genes involved in metabolic disorders.

BMC Genomics, 2015

Background: Otitis media is the most common disease of childhood, and represents an important hea... more Background: Otitis media is the most common disease of childhood, and represents an important health challenge to the 10-15% of children who experience chronic/recurrent middle ear infections. The middle ear undergoes extensive modifications during otitis media, potentially involving changes in the expression of many genes. Expression profiling offers an opportunity to discover novel genes and pathways involved in this common childhood disease. The middle ears of 320 WBxB6 F1 hybrid mice were inoculated with non-typeable Haemophilus influenzae (NTHi) or PBS (sham control). Two independent samples were generated for each time point and condition, from initiation of infection to resolution. RNA was profiled on Affymetrix mouse 430 2.0 whole-genome microarrays. Results: Approximately 8% of the sampled transcripts defined the signature of acute NTHi-induced otitis media across time. Hierarchical clustering of signal intensities revealed several temporal gene clusters. Network and pathway enrichment analysis of these clusters identified sets of genes involved in activation of the innate immune response, negative regulation of immune response, changes in epithelial and stromal cell markers, and the recruitment/function of neutrophils and macrophages. We also identified key transcriptional regulators related to events in otitis media, which likely determine the expression of these gene clusters. A list of otitis media susceptibility genes, derived from genome-wide association and candidate gene studies, was significantly enriched during the early induction phase and the middle re-modeling phase of otitis but not in the resolution phase. Our results further indicate that positive versus negative regulation of inflammatory processes occur with highly similar kinetics during otitis media, underscoring the importance of anti-inflammatory responses in controlling pathogenesis. Conclusions: The results characterize the global gene response during otitis media and identify key signaling and transcription factor networks that control the defense of the middle ear against infection. These networks deserve further attention, as dysregulated immune defense and inflammatory responses may contribute to recurrent or chronic otitis in children.

Annals of Allergy, Asthma & Immunology, 2015

African Americans disproportionally experience uncontrolled asthma 1. Because asthma control is n... more African Americans disproportionally experience uncontrolled asthma 1. Because asthma control is now the focus of asthma management, 2 publicly available questionnaires like the Asthma Control Test ™ (ACT) 3 and childhood Asthma Control Test (ACTc) 4 represent the

Innate immunity, 2012

Otitis media (OM), a common infectious disease in children, is associated with bacterial middle e... more Otitis media (OM), a common infectious disease in children, is associated with bacterial middle ear (ME) infection. Toll-like receptors (TLRs) are important mediators of innate immune responses, and TLR9 specifically recognizes the unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacterial DNA. Additional sensors of foreign DNA have recently been identified. The role of DNA sensing and TLR9 was investigated in a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). Expression of genes related to DNA-sensing pathways involved in innate immunity was assessed via DNA microarray, qPCR and immunohistochemistry. Middle ear responses to NTHi were examined in wild-type and TLR9(-/-) mice by histopathology and bacterial culture. Expression of TLR9 signaling genes was modestly up-regulated during OM, as was TLR9 protein in both ME mucosal cells and infiltrating leukocytes. However, genes known to be regulated by CpG DNA were dramatically up-regulated, as were gene...

Current Allergy and Asthma Reports, 2006

Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of human immunity and... more Primary immunodeficiency disorders (PIDs) continue to illuminate mechanisms of human immunity and hypersensitivity. New discoveries in common variable immunodeficiency, the most enigmatic of PID syndromes, reveal molecular pathways of importance in human antibody production. FOXP3 mutations demonstrate the essential role that T-regulatory cells play in controlling autoantibody formation and disease. Interleukin-1 receptor-associated kinase 4 deficiency emphasizes the key role that innate immunity plays in the defense of bacterial disease occurring early in life. With respect to therapy, subcutaneous immunoglobulin treatment may indeed be a better treatment than intravenous immunoglobulin for many patients with antibody deficiency. Finally, PIDs remain in the vanguard for the treatment of inherited disorders by gene therapy. Gene therapy has cured patients with chronic granulomatous disease and severe combined immunodeficiency, but not without morbidity and mortality. Into the 21st century, PIDs continue to instruct us in human health and disease.

Pediatric Transplantation, 2009

OS is an inherited disorder characterized by immunodeficiency, diffuse erythroderma, hepatospleno... more OS is an inherited disorder characterized by immunodeficiency, diffuse erythroderma, hepatosplenomegaly, lymphadenopathy, protracted diarrhea, and failure to thrive. It was first described by Gilbert S. Omenn in 1965 (1). The report centered on an inbred Irish Catholic family whose family history was significant for 12 infants that died with similar clinical features. The propositus of the report presented at 33 days of age with a generalized erythematous papular and vesicular skin eruption, chronic diarrhea, hepatomegaly, conjunctivitis, and mild fevers, with laboratory findings significant for eosinophilia. During the course of the infantÕs hospital stay, he developed multiple infections and eventually died of respiratory and cardiac failure. Autopsy demonstrated pneumonitis secondary to Pneumocystis carinii, bilateral otitis media and inflammatory infiltrates in the lymph nodes, skin, liver, and spleen. Pedigree analysis of the family demonstrated the syndrome to be inherited in an autosomal recessive manner. Since that initial report, inherited mutations in either of the recombination activating genes RAG1 or RAG2, resulting in partial V(D)J recombinase activity, have been shown to be responsible for many cases of OS, although there is significant clinical and genetic heterogeneity