About

Shaon Sengupta, MBBS, MPH, FAAP, is an Assistant Professor of Pediatrics specializing in Neonatology and Newborn Services at the Perelman School of Medicine, University of Pennsylvania. He is an attending physician in Neonatal-Perinatal Medicine at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. Dr. Sengupta is affiliated with the Institute of Translational Medicine and Therapeutics at the University of Pennsylvania. His educational background includes an MBBS from the All India Institute of Medical Sciences, India, obtained in 2006, and a Master of Public Health from Johns Hopkins Bloomberg School of Public Health, completed in 2008. His clinical expertise encompasses neonatology, ECMO, and NRP. His research focuses on circadian biology, lung inflammation, neonatal lung injury, influenza, lung regeneration, and lung organoids. Dr. Sengupta's work aims to understand immune regulation and pulmonary signaling in neonatal and infectious disease contexts, contributing to advancements in neonatal care and translational medicine.

Research topics

• Computer Science
• Biology
• Immunology
• Neuroscience

Selected publications

• Maternal and perinatal nutritional programming of lung health and disease in childhood and early adulthood: Research gaps and opportunities—National Heart, Lung, and Blood Institute/National Institutes of Health Workshop Report

  Journal of Allergy and Clinical Immunology · 2026-04-01

  article
  PublisherDOI

• Role of IL10 signaling in the circadian control of host response to Influenza infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-10

  preprintOpen accessSenior authorCorresponding

  Abstract We have previously demonstrated that the circadian clock regulates the host response to influenza A virus (IAV) infection, conferring a time-of-day-specific protection –infection at dawn resulted in a threefold increase in survival and reduced immunopathology compared to infection at dusk. While IL10 is well-known for its immunoregulatory function, its role in IAV remains unclear, with studies reporting both protective and detrimental effects. Given the diurnal rhythmicity of IL-10 receptor ( Il10ra ) expression in the lung, we investigated the contribution of IL-10 signaling to time-of-day-specific IAV protection. We found that blocking IL10 signaling abrogated the time of day protection, leading to increased immunopathology characterized by enhanced lymphocyte infiltration and global immune activation (transcriptomic analysis). Interestingly, while later, IL-10R blockade also eliminated the time-of-day difference in IAV outcomes, it improved the outcome of dusk-infected mice. Furthermore, natural killer (NK) cell depletion suppressed IL-10 levels in bronchoalveolar lavage, suggesting a role for NK cells in regulating IL-10 signaling. In conclusion, incorporating the circadian context has not only clarified the IL-10 role in IAV infection but also underscored the pivotal influence of circadian regulation on immune responses.

  PublisherOA PDFDOI

• Circadian Control of Pulmonary Endothelial Signaling Occurs via the NADPH Oxidase 2-NLRP3 Pathway

  Journal of Biological Rhythms · 2025-09-14

  articleOpen access1st authorCorresponding

  Circadian rhythms are endogenous oscillations that occur with a 24-h periodicity and support organismal homeostasis. While the role of the circadian clock in systemic vasculature is well known, its role in pulmonary vasculature, specifically in the pulmonary endothelium, has remained unexplored. We hypothesized that the circadian clock directly regulates pulmonary endothelium to control lung inflammation. Using pulmonary artery segments and endothelial cells isolated from lungs of mPer2luciferase transgenic mice, we monitored circadian rhythms and observed that lipopolysaccharide (LPS) treatment disrupted rhythmicity. This disruption was mediated by reactive oxygen species (ROS) generated via NADPH oxidase 2 (NOX2). Remarkably, the pharmacologic inhibition of NOX2 before LPS exposure restored circadian rhythmicity in the pulmonary endothelium. In wild-type (WT) mice, LPS activated a NOX2-NLRP3 signaling axis that drove inflammation as evidenced by increased polymorphonuclear neutrophil (PMN) accumulation and intercellular adhesion molecule-1 (ICAM-1) expression on the pulmonary endothelium. In contrast, disruption of the clock using two different clock mutants ( Bmal 1 –/– and Cry1/2 –/– ) resulted in a sustained baseline elevation of PMN and ICAM-1, which changed minimally with LPS. This effect was attributed to aberrant activation of the NLRP3 inflammasome at baseline in the clock mutants, as supported by lung transcriptomic data and reversal of the phenotype with an NLRP3 inhibitor. Importantly, these findings also reveal an intriguing bidirectional relationship: while the circadian clock modulates inflammatory responses, inflammatory stimuli in turn alter circadian rhythmicity via the NOX2 pathway. Together, our results identify a novel mechanism by which circadian control of pulmonary endothelial inflammation may be leveraged to mitigate the consequences of clock disruption in lung disease.

  PublisherDOI

• Effect of external cues on clock-driven protection from Influenza A infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-11

  preprintOpen accessSenior authorCorresponding

  Abstract Influenza and other respiratory viral pathogens are leading causes of mortality and morbidity. We previously demonstrated that circadian rhythms confer temporal protection from influenza infection. Here, we investigated whether this protection requires rhythmic function after the initial infection by manipulating environmental cycles. We demonstrate that disrupting environmental lighting cues within a critical window of vulnerability abrogates time-of-day specific protection. This poor outcome is mediated by a dysregulated immune response, evidenced by the accumulation of inflammatory monocytes and CD8 + cells in the lungs and a transcriptomic profile indicative of an exaggerated immune response. Disruption of the light cycle does not affect outcomes in a clock mutant, indicating that it acts by compromising endogenous timekeeping. Importantly, rhythmic meal timing mitigates the adverse effects of disrupted light cycles, suggesting that external cycling cues, which act through different body clocks, can substitute for each other. Our findings highlight the crucial interplay between environmental factors and endogenous clocks in shaping influenza outcomes, offering significant translational potential for improving the care of critically ill patients with respiratory viral infections.

  PublisherOA PDFDOI

• Role of IL-10 signaling in the circadian control of host response to influenza infection

  Mucosal Immunology · 2025-11-21

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Sources of non-uniform coverage in short-read RNA-Seq data

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-31 · 2 citations

  preprintOpen access

  The origin of several normal cellular functions and related abnormalities can be traced back to RNA splicing. As such, RNA splicing is currently the focus of a vast array of studies. To quantify the transcriptome, short-read RNA-Seq remains the standard assay. The primary technical artifact of RNASeq library prep, which severely interferes with analysis, is extreme non-uniformity in coverage across transcripts. This non-uniformity is present in both bulk and single-cell RNA-Seq and is observed even when the sample contains only full-length transcripts. This issue dramatically affects the accuracy of isoform-level quantification of multi-isoform genes. Understanding the sources of this non-uniformity is critical to developing improved protocols and analysis methods. Here, we explore eight potential sources of non-uniformity. We demonstrate that it cannot be explained by one factor alone. We performed targeted experiments to investigate the effect of fragment length, PCR ramp rate, and ribosomal depletion. We assessed existing data sets with varying sample quality, PCR cycle number, reverse transcriptase, and technical or biological replicates. We found evidence that interference of reverse transcription by secondary structure is unlikely to be the major contributing factor, that rRNA pull-down methods do not cause non-uniformity, that PCR ramp rate does not substantially impact non-uniformity, and that shorter fragments do not reduce non-uniformity. All these findings contradict prior publications or recommendations.

  PublisherOA PDFDOI

• Microbiota-derived inosine programs protective CD8+ T cell responses against influenza in newborns

  Cell · 2025-06-09 · 14 citations

  article
  PublisherDOI

• Effect of external cues on clock-driven protection from influenza A infection

  Journal of Clinical Investigation · 2025-11-16

  articleOpen accessSenior author

  Influenza and other respiratory viral pathogens remain leading causes of mortality and morbidity. Circadian rhythms play a critical role in regulating immune responses and can confer temporal protection from influenza infection. Here, we investigated whether this protection requires rhythmic function after the initial infection by manipulating environmental cycles. We found that disrupting environmental lighting cues within a critical window of vulnerability abrogated the time-of-day-specific protection. This poor outcome was mediated by a dysregulated immune response, as evidenced by the accumulation of inflammatory monocytes and CD8+ T cells in the lungs and a transcriptomic profile indicative of an exaggerated inflammation. Disruption of the light cycle did not affect outcomes in a clock mutant, indicating that it acts through the host's circadian clock. Importantly, rhythmic meal timing mitigated the adverse effects of disrupted light cycles, supporting the idea that external cues acting through different body clocks can compensate for one another. Together, these findings underscore the critical interplay between environmental timing cues and endogenous circadian rhythms in determining influenza outcomes and offer translational insight into optimizing care for critically ill patients with respiratory viral infections.

  PublisherDOI

• Identification of distinct genotypes in circulating RSV A strains based on variants in the virus replication-associated genes

  Journal of Virology · 2024-07-15 · 3 citations

  articleOpen access

  ABSTRACT Respiratory syncytial virus (RSV) is a common cause of respiratory infection that often leads to hospitalization of infected younger children and older adults. RSV is classified into two strains, A and B, each with several subgroups or genotypes. One issue with the definition of these subgroups is the lack of a unified method of identification or genotyping. We propose that genotyping strategies based on the genes coding for replication-associated proteins could provide critical information on the replication capacity of the distinct subgroups, while clearly distinguishing genotypes. Here, we analyzed the virus replication-associated genes N, P, M2, and L from de novo assembled RSV A sequences obtained from 31 newly sequenced samples from hospitalized patients in Philadelphia and 78 additional publicly available sequences from different geographic locations within the United States. In-depth analysis and annotation of variants in the replication-associated proteins identified the polymerase protein L as a robust target for genotyping RSV subgroups. Importantly, our analysis revealed non-synonymous variations in L that were consistently accompanied by conserved changes in its co-factor P or the M2-2 protein, suggesting associations and interactions between specific domains of these proteins. Similar associations were seen among sequences of the related human metapneumovirus. These results highlight L as an alternative to other RSV genotyping targets and demonstrate the value of in-depth analyses and annotations of RSV sequences as it can serve as a foundation for subsequent in vitro and clinical studies on the efficiency of the polymerase and fitness of different virus isolates. IMPORTANCE Given the historical heterogeneity of respiratory syncytial virus (RSV) and the disease it causes, there is a need to understand the properties of the circulating RSV strains each season. This information would benefit from an informative and consensus method of genotyping the virus. Here, we carried out a variant analysis that shows a pattern of specific variations among the replication-associated genes of RSV A across different seasons. Interestingly, these variation patterns, which were also seen in human metapneumovirus sequences, point to previously defined interactions of domains within these genes, suggesting co-variation in the replication-associated genes. Our results also suggest a genotyping strategy that can prove to be particularly important in understanding the genotype-phenotype correlation in the era of RSV vaccination, where selective pressure on the virus to evolve is anticipated. More importantly, the categorization of pneumoviruses based on these patterns may be of prognostic value.

  PublisherDOI

• BEERS2: RNA-Seq simulation through high fidelity <i>in silico</i> modeling

  Briefings in Bioinformatics · 2024-03-26 · 5 citations

  articleOpen access

  Simulation of RNA-seq reads is critical in the assessment, comparison, benchmarking and development of bioinformatics tools. Yet the field of RNA-seq simulators has progressed little in the last decade. To address this need we have developed BEERS2, which combines a flexible and highly configurable design with detailed simulation of the entire library preparation and sequencing pipeline. BEERS2 takes input transcripts (typically fully length messenger RNA transcripts with polyA tails) from either customizable input or from CAMPAREE simulated RNA samples. It produces realistic reads of these transcripts as FASTQ, SAM or BAM formats with the SAM or BAM formats containing the true alignment to the reference genome. It also produces true transcript-level quantification values. BEERS2 combines a flexible and highly configurable design with detailed simulation of the entire library preparation and sequencing pipeline and is designed to include the effects of polyA selection and RiboZero for ribosomal depletion, hexamer priming sequence biases, GC-content biases in polymerase chain reaction (PCR) amplification, barcode read errors and errors during PCR amplification. These characteristics combine to make BEERS2 the most complete simulation of RNA-seq to date. Finally, we demonstrate the use of BEERS2 by measuring the effect of several settings on the popular Salmon pseudoalignment algorithm.

  PublisherOA PDFDOI

Recent grants

• Role of Circadian Clock in Lung Inflammation

  NIH · $638k · 2017–2021

Frequent coauthors

• Amruta Naik

  44 shared

• Soon Yew Tang

  California University of Pennsylvania

  44 shared

• Garret A. FitzGerald

  Translational Therapeutics (United States)

  38 shared

• Katherine N. Theken

  University of Pennsylvania

  28 shared

• Thomas G. Brooks

  27 shared

• Gregory R. Grant

  Translational Therapeutics (United States)

  26 shared

• Kaitlyn Forrest

  California University of Pennsylvania

  25 shared

• Nicholas F. Lahens

  Translational Therapeutics (United States)

  23 shared

Labs

• Shaon Sengupta LabPI