Publications

The COVID-19 pandemic was accompanied by a 60% increase alcohol consumption, alcohol-related deaths, and COVID-19 severity. This manuscript showed that chronic heavy drinking results in aberrant inflammation and reduced antiviral responses in the lung to SARS-CoV-2 infection within the lung.

Chronic heavy alcohol drinking results in  heightened inflammatory but compromised antimicrobial responses by monocytes and macrophages. In this article we show that  these changes persist after 1-month abstinence suggesting alteration in hematopoietic stem cells (HSC). Indeed, scRNA and snATAC sequencing revealed significant shifts in the transcriptional and epigentic landscape of HSC that are poised to produce hyper-inflammatory monocytes.

Recent studies have utilized extracellular vesicle-bound microRNAs (EV-miRNAs) as biomarkers for various disease states. In this study, we identified several EV-miRNAs that could serve as biomarkers of long-term alcohol drinking.

Chronic alcohol drinking is associated with susceptibility to bacterial and viral respiratory pathogens. In this article we demonstrate a heightened inflammatory state in alveolar macrophages, disruption of antimicrobial defenses, and an increase oxidative stress with chronic ethanol consumption.

Chronic heavy drinking (CHD) results in heightned inflammatory responses by monocytes. In this article, we use scRNA sequencing to demonstrate shifts in classical monocyte subset composition that primes the monocytes towards a more hyper-inflammatory response to LPS, but compromised pathogen response.

Campylobacter spp., a major cause of diarrheal diseases, remain one of the leading causes of morbidity and mortality for children under the age of 5 year, especially in low and middle income countries. Here, we report several novel metagenomically assembled Campylobacter genomes that predispose infant to develop diarrhea and is correlated with microbiome immaturity.

Enteric disease caused by Campylobacter is responsible for the development of gastroenteritis and growth stunting of infants. In this article, we demonstrate that Campylobacter vaccination reduces all cause diarrheal disease and is potentially an effective intervention to improves infant growth.

A myriad of metabolic and physiological adaptations are needed to support fetal growth and maternal health. We report significant shifts in the taxonomic landscape and functional potential of the maternal gut microbiome during the transition from pregnancy to postpartum including increase in short-chain fatty acid butyrate, starch degradation and folate transformation in line with the increased metabolic demands imposed by breastfeeding.

Vaginal microbiota is important for women’s reproductive and urogenital health and is typically dominated by Lactobacillus species. In this article, we demonstrate the utility of macaques as a model to study diverse vaginal communities and test interventions for manipulating the vaginal microbiome.

Tai Forest virus (TAFV) is a memner of the Filoviridae family. Unlike other members of this family such as Ebola virus (EBOV), TAFV has only been associated with a single human case during an outbreak in chimpanzees in West Africa. This study examines the host response in cynomolgus macaques of two different TAFV strains that have different pathogenicity profiles.

Despite being a respiratory pathogen, the mechanisms by which Varicella zoster virus (VZV), the causative agent of chickenpox and shingles disseminates from the respiratory tract to the sensory ganglia where it establishes latency remain unclear. Given the difficulty in obtaining clinical samples, we leveraged a rhesus macaque experimental model where animals are intrabronchially infected with Simian varicella virus (SVV). Our analysis revealed that SVV acute infection results in dramatic remodeling of the alveolar space by altering macrophage and T cell populations. Moreover, genes associated with cellular metabolism and tissue homing were differentially expressed in infected cells suggesting adaptations to support viral replication. Given the close homology between VZV and SVV, our findings have important implications for understanding VZV pathogenesis as well as potential complications and secondary infections.

Marburg virus disease (MVD) results in highly fatal haemorrhagic disease and has no licensed vaccine or therapeutic. In this study, we profiled the transcriptional response to a low dose vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) 14 or 7 days before challenge. Our results indicate that length of time between vaccination and challenge modulates vaccine responses, but that low dose VSV-MARV vaccination can be deployed to contain outbreaks.

RNA polymerase III  transcribes short interspersed nuclear elements (SINE) which can be induced in response to viral infections and can stimulate immune signaling pathways. In this article we show that RNA Pol III silencing alters the antiviral transcriptional program, indicative of an important role for

This study shows that asymptomatic/mild SARS-CoV-2 infection remodels the immune landscape at the maternal-fetal interface leading to expansion of activated macrophages and T cells in line with an antiviral response despite the lack of direct infection of the placenta.  

Nontuberculous mycobacteria (NTM) are environmentally ubiquitous organisms that cause pulmonary disease (NTMPD) primarily in individuals over the age of 65. The mechanisms underlying age-mediated increase in susceptibity are poorly understood. In this article, we show for the first time that rhesus macaque recapitulate the age-mediated increase in disease severity and define the impact of age on the histopathology, dysbiosis, and immune response to NTM infection.

Despite the understanding that older individuals are at increased risk of developing severe respiratory infections, the molecular mechanism of aging on the respiratory tract is undefined. Here we define the consequences of aging on the lung using the rhesus macaque model and show shifts in cell frequency and cytokine production.

In this article we define the phenotypical, transcriptional and functional impact of age on the immune response to SARS-CoV-2 infection. We identified an association between reduced frequency of antigen-specific B cells and memory T cells, as well as, the emergence of suppressive monocytes as  and COVID-19 outcomes.

The average age of individuals living with HIV has significantly increased with the introduction of highly active antiretroviral therapy (HAART). In this article we define the shifts in immune cell frequencies and gut microbial communities with long-term controlled (LTC) HIV.

In this article we define the impact of maternal asymptomatic/mild SARS-CoV-2 infection on the maturation of the neonatal immune system. We report increased systemic inflammation, as well as increased frequency of memory T and B cells indicative of aberrant in utero activation. However, the ability of T cells and monocytes to respond to stimulus was dampened, akin to immune tolerance. Finally, we also report changes in the abundance of Hoffbauer cells and infiltrating maternal macrophages within the chorionic villous that was accompanied by heightened inflammatory signatures.

Maternal obesity is associated with increased susceptibility and severity of neonatal infections. In this study, we show that pregravid obesity dampens umbilical cord blood monocyte responses to bacterial and viral pathogens. These responses were mediated by alterations in the transcriptional landscape as well as reduced chromatin accessibility within UCB monocytes.

The immune landscape of first-trimester maternal-fetal interface has been extensively studied. Here, we profiled the immunological landscape of the term decidua to define shifts in cell population frequencies and function at term relative to first trimester. Additionally, we showed that maternal macrophages are skewed toward immunoregulation with high maternal BMI.

Pregravid obesity has been shown to disrupt the development of the offspring’s immune system and increase susceptibility to infection. In this article we demonstrated that maternal western style diet impairs fetal HSPC differentiation and function of myeloid cells.

Maternal pregravid obesity is linked to increased neonatal infections and need for admission to the intensive care unit. We have already shown that pregravid obesity dampens umbilical cord blood monocytes’ response to bacterial ligands. Here, we extend these observations and show that despite increased abundance of memory CD4 T cells, response to T cell receptor stimulation were reduced in part due to increased DNA methylation and decreased chromatin accessibility at key loci associated with T cell activation.