Suman Pakala

Vanderbilt University | Vander Bilt · Department of Medicine

Background The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesi...

Background: High salt consumption is associated with increased cardiovascular risk and higher morbidity and mortality in salt-sensitive hypertensives than in salt-resistant normotensives. Salt sensitivity of blood pressure (SSBP) is an independent predictor of death due to cardiovascular disease. Although the role of SMAD3 has been extensively stud...

Persistent systemic inflammation in persons with HIV (PWH) is accompanied by an increased risk of metabolic disease. Yet, changes in the innate and adaptive immune system in PWH who develop metabolic disease remain poorly defined. Using unbiased approaches, we show that PWH with prediabetes/diabetes have a significantly higher proportion of circula...

Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in card...

Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity.

Previous studies have suggested that a relationship exists between severity and transmissibility of malaria and variations in the gut microbiome, yet only limited information exists on the temporal dynamics of the gut microbial community during a malarial infection. Here, using a rhesus macaque model of relapsing malaria, we investigate how malaria...

Both Helicobacter pylori infection and a high-salt diet are risk factors for gastric cancer. We previously showed that a mutation in fur (encoding the ferric uptake regulator variant Fur-R88H) was positively selected in H. pylori strains isolated from experimentally infected Mongolian gerbils receiving a high-salt diet. In the present study, we rep...

Background To characterize how antibiotic exposure impacts development and durability of intestinal dysbiosis and the acquisition of antibiotic resistance genes (ARGs) in the intestinal flora of premature infants in the Neonatal Intensive Care Unit (NICU), we established an infant gut microbiome biorepository (IGMB). Methods We performed prospecti...

Background: COVID-19 prevalence has remained high throughout the pandemic with intermittent surges, due largely to the emergence of genetic variants, demonstrating the need for more accessible sequencing technologies for strain typing. Methods: A ligation-based typing assay was developed to detect known variants of severe acute respiratory syndr...

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale . Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal sy...

The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for respiratory syncytial virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to generate a...

Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 6...

Background Salt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel En...

Background: The cotton rat (Sigmodon) is the gold standard pre-clinical small animal model for respiratory viral pathogens, especially for Respiratory Syncytial Virus (RSV). However, without a reference genome or a published transcriptome, studies requiring gene expression analysis in cotton rats are severely limited. The aims of this study were to...

Salt-sensitivity of blood pressure affects 50% of hypertensive and 25% of normotensive individuals and is an independent predictor of death due to cardiovascular disease. We recently found that gamma and alpha subunits of the epithelial sodium channel (ENaCαγ) on dendritic cells mediate NADPH oxidase-dependent formation of immunogenic isolevuglandi...

To elucidate the molecular mechanisms manifesting lung abnormalities during severe SARS-CoV-2 infections, we performed whole transcriptome sequencing of lung autopsies from 31 patients with severe COVID-19 and 10 uninfected controls. Using metatranscriptomics, we identified the existence of two distinct molecular signatures of lethal COVID-19. The...

The Omicron variant of SARS‐CoV‐2 achieved worldwide dominance in late 2021. Early work suggests that infections caused by the Omicron variant may be less severe than those caused by the Delta variant. We sought to compare clinical outcomes of infections caused by these two strains, confirmed by whole genome sequencing, over a short period of time,...

The precise molecular mechanisms behind severe life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome...

We developed a metatranscriptomics method that can simultaneously capture the respiratory virome, microbiome, and host response directly from low biomass samples. Using nasal swab samples, we capture RNA virome with sufficient sequencing depth required to assemble complete genomes. We find a surprisingly high frequency of respiratory syncytial viru...

Salt sensitivity of blood pressure is an independent predictor of death due to cardiovascular events. Diagnosis of salt-sensitivity is not feasible in the clinic, making it difficult to investigate therapeutic strategies. We hypothesized that NLRP3-inflammasome and IL-1β production in monocytes plays a role in salt-sensitive hypertension. We phenot...

Background: Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host's anti-viral immune response, in turn affecting the frequency of variants over time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of th...

Rising global temperatures have caused a substantial loss in crop productivity throughout the world. Understanding the fundamental mechanisms underlying tolerance to heat stress in plants has become increasingly relevant, particularly as global warming continues to rise. The goal of our study was to identify and analyze heat stress-induced transcri...

We developed a metatranscriptomics method that can simultaneously capture the respiratory virome, microbiome, and host response directly from low-biomass clinical samples. Using nasal swab samples, we have demonstrated that this method captures the comprehensive RNA virome with sufficient sequencing depth required to assemble complete genomes. We f...

Projects in the life sciences continue to increase in complexity as they scale to answer deeper and more diverse questions. They employ technologies that generate increasingly large ‘omic’ datasets and research teams regularly include experts ranging from animal care technicians, veterinarians, human health clinicians, geneticists, immunologists, a...

Background Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host’s anti-viral immune response, in turn affecting the frequency of variants over-time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the...

Here, we report 17 nearly complete genome sequences of enterovirus D68 (EV-D68) isolated from Kansas City, MO, in 2018. Phylogenetic analysis suggests that these strains belong to subclade B3, similar to the ones that caused the 2016 epidemics in the United States but different from the 2014 outbreak B1 strains.

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create...

Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not k...

After publication of the article [1], it was brought to our attention that several symbols were missing from Fig. 1, including some cited in the figure’s key. The correct version of the figure is shown below and has now been updated in the original article.

Background Mild to severe anaemia is a common complication of malaria that is caused in part by insufficient erythropoiesis in the bone marrow. This study used systems biology to evaluate the transcriptional and alterations in cell populations in the bone marrow during Plasmodium cynomolgi infection of rhesus macaques (a model of Plasmodium vivax m...

Cockroach allergens can lead to serious allergy and asthma symptoms. Termites are evolutionarily related to cockroaches, cohabitate in human dwellings, and represent an increasing pest problem in the United States. The Formosan subterranean termite (Coptotermes formosanus) is one of the most common species in the southern United States. Several ass...

Uncropped immunoblots used in Fig 2A. (JPG)

Uncropped immunoblots used in Fig 4A. (JPG)

Phylogenetic tree of hexamerin and hemocyanin proteins. Hexamerin and hemocyanin proteins from 8 species, including the German cockroach Bla g 3 and the American cockroach Per a 3 allergens, were compared with 2 putative C. formosanus hemocyanin proteins (1481.m000238 and 1481.m000236) using the multiple alignment search with the BLASTP suite at nc...

Phylogenetic tree of arginine kinase proteins. German and American cockroach arginine kinase proteins (Bla g 9 and Per a 9) along with 7 other allergenic arginine kinase proteins included in the IUIS website listed under Animalia Arthropoda were compared with 2 putative C. formosanus tropomyosin proteins (4552.m000111 and 1950.m000177) using the mu...

Uncropped immunoblots used in Fig 2C. (JPG)

Predicted Coptotermes formosanus termite proteins homologous to cockroach allergens. Coptotermes formosanus (Cf) termite protein and nucleotide sequences of predicted cockroach allergen homologs. (DOC)

Uncropped immunoblots used in Fig 2B. (JPG)

Phylogenetic tree of tropomyosin proteins. German and American cockroach tropomyosin proteins (Bla g 7 and Per a 7) along with 22 other allergenic tropomyosin proteins included in the IUIS website listed under Animalia Arthropoda were compared with 2 putative C. formosanus tropomyosin proteins (1264.m000365 and 4474.m000137) using the multiple alig...

Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large...

Background: Plasmodium vivax infections in humans or in new world monkeys pose research challenges that necessitate the use of alternative model systems. Plasmodium cynomolgi is a closely related species that shares genetic and biological characteristics with P. vivax, including relapses. Here, the haematological dynamics and clinical presentation...

Plasmodium coatneyi is a protozoan parasite species that causes simian malaria and is an excellent model for studying disease caused by the human malaria parasite, P. falciparum Here we report the complete (nontelomeric) genome sequence of P. coatneyi Hackeri generated by the application of only Pacific Biosciences RS II (PacBio RS II) single-molec...

Invasive aspergillosis (IA) due to Aspergillus fumigatus is a major cause of mortality in immunocompromised patients. The discovery of highly fertile strains of A. fumigatus opened the possibility to merge classical and contemporary genetics to address key questions about this pathogen. The merger involves sexual recombination, selection of desired...

Rhizoctonia solani is a plant pathogenic fungus that causes black scurf on tubers and stem and stolon canker on underground parts of potato plant. Early in the season, the fungus attacks germinating sprouts underground before they emerge from the soil. Damage at this stage results in delayed emergence of weakened plants with poor and uneven stands....

The soil fungus Rhizoctonia solani is a pathogen of agricultural crops. Here, we report on the 51,705,945 bp draft consensus genome sequence of R. solani strain Rhs1AP. A comprehensive understanding of the heterokaryotic genome complexity and organization of R. solani may provide insight into the plant disease ecology and adaptive behavior of the f...

Iron plays a critical role in survival and virulence of the opportunistic pathogen Aspergillus fumigatus. Two transcription factors, the GATA-factor SreA and the bZip-factor HapX oppositely monitor iron homeostasis with HapX activating iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive pathways (and SreA) during iron...

We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta). Whole blood and bone marrow (BM) RNA-Seq and plasma metabolome profiles (each with over 15,000 features) have been generated for five naïve individuals at up to seven timepoints befor...

We utilized RNAseq analysis of the Aspergillus fumigatus response to early hypoxic condition exposure. The results show that more than 89 % of the A. fumigatus genome is expressed under normoxic and hypoxic conditions. Replicate samples were highly reproducible; however, comparisons between normoxia and hypoxia revealed that >23 and 35 % of genes w...

Efforts to map the Escherichia coli interactome have identified several hundred macromolecular complexes, but direct binary protein-protein interactions (PPIs) have not been surveyed on a large scale. Here we performed yeast two-hybrid screens of 3,305 baits against 3,606 preys (∼70% of the E. coli proteome) in duplicate to generate a map of 2,234...

The soil fungus Rhizoctonia solani is an economically important pathogen of agricultural and forestry crops. Here we present the complete sequence and analysis of the mitochondrial genome of R. solani, field isolate Rhs1AP. The genome (235,849 bp) is the largest mitochondrial genome of a filamentous fungus sequenced to date and exhibits a rich accu...

Rhizoctonia solani agglutinin (RSA) is a 15.5-kDa lectin accumulated in the mycelium and sclerotia of the soil born plant pathogenic fungus R. solani. Although it is considered to serve as a storage protein and is implicated in fungal insecticidal activity, its physiological role remains unclear as a result of a lack of any structure/function relat...