David A. Constant

ORCID: 0000-0001-9656-078X
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About
Contact & Profiles
Research Areas
  • Viral gastroenteritis research and epidemiology
  • Respiratory viral infections research
  • Cytokine Signaling Pathways and Interactions
  • Infection Control and Ventilation
  • interferon and immune responses
  • Immune Response and Inflammation
  • Mosquito-borne diseases and control
  • Clostridium difficile and Clostridium perfringens research
  • Immune Cell Function and Interaction
  • Malaria Research and Control
  • Gut microbiota and health
  • Animal Virus Infections Studies
  • COVID-19 and healthcare impacts
  • HIV Research and Treatment
  • Virus-based gene therapy research
  • Regional Development and Policy
  • Toxic Organic Pollutants Impact
  • Infection Control in Healthcare
  • Protein purification and stability
  • vaccines and immunoinformatics approaches
  • Dental Research and COVID-19
  • Inflammasome and immune disorders
  • COVID-19 Impact on Reproduction
  • Inflammatory Bowel Disease
  • Insect symbiosis and bacterial influences

Oregon Health & Science University
2020-2025

University of Oregon
2020

Stanford University
2018-2020

Community Link
2020

Reed College
2012

Louisiana State University
1996

Salmonella enterica serovar Typhimurium is a Gram-negative pathogen that causes diseases ranging from gastroenteritis to systemic infection and sepsis. uses type III secretion systems (T3SS) inject effectors into host cells. While these are necessary for bacterial invasion intracellular survival, delivery of T3SS products also enables detection translocated ligands by cytosolic immune sensors. Some sensors form multimeric complexes called inflammasomes, which activate caspases lead...

10.1128/iai.00663-21 article EN Infection and Immunity 2022-06-09

Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine specific pathogen-free mice. This is restricted to IECs, depends on IEC-intrinsic IFN-λ receptor ( Ifnlr1 ), and associated with production leukocytes. Strikingly, imaging these ISGs reveals localization pockets epithelium concentration mature...

10.7554/elife.74072 article EN cc-by eLife 2022-02-09

Current literature values of 2,4,6-trinitrotoluene (TNT) solubility in water vary widely from 100 to 200 mg/L at room temperature. We investigated the effects temperature and pH on both reference TNT field neat obtained Alabama Army Ammunition Plant (AAAP), Childersburg, AL. The determined this study was significantly lower than that Taylor Rinkenbach, which cited by several chemical handbooks articles. However, reported Merck Index Lange's Handbook Chemistry compared well with our values....

10.1021/je950322w article EN Journal of Chemical & Engineering Data 1996-01-01

Evidence continues to grow supporting the aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess potential role heating, ventilation, and air conditioning (HVAC) systems in airborne viral transmission, this study sought determine presence, if any, on handling units a healthcare setting where disease 2019 (COVID-19) patients were being treated. The presence SARS-CoV-2 RNA was detected approximately 25% samples taken from ten different locations...

10.1111/ina.12898 article EN Indoor Air 2021-06-29

Significance Inhibitors of dengue virus, a mosquito-borne pathogen, are urgently needed. Virally encoded NS2B/3, two-subunit serine proteinase, is responsible for many cleavages within the viral polyprotein. We demonstrate that two cleavage sites flanking NS3 and one internal self-processing. This strict intramolecular dictates that, if uncleaved precursors can inhibit growth, this phenotype will be trans -dominant. Indeed, mutation abrogates self-processing caused -dominant inhibition...

10.1073/pnas.1805195115 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2018-09-18

Enteric viral infections are a major cause of gastroenteritis worldwide and have the potential to trigger or exacerbate intestinal inflammatory diseases. Prior studies identified specialized innate immune responses that active in epithelium following infection, but our understanding benefits such an epithelium-specific response is incomplete. Here, we show epithelial antiviral programmed enable protection while minimizing cytotoxicity can often accompany response. Our findings offer new...

10.1128/jvi.00603-20 article EN Journal of Virology 2020-08-24

Abstract Increasing recombinant protein expression is of broad interest in industrial biotechnology, synthetic biology, and basic research. Codon optimization an important step heterologous gene that can have dramatic effects on level. Several codon strategies been developed to enhance expression, but these are largely based bulk usage highly frequent codons the host genome, produce unreliable results. Here, we develop deep contextual language models learn rules from natural coding sequences...

10.1101/2023.02.11.528149 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-02-12

Cell-intrinsic antiviral gene expression by intestinal epithelial cells (IECs) limits infection enteric viral pathogens. Here, we find that neonatal IECs express genes at homeostasis depend on interferon lambda (IFN-λ) and are required for early control of mouse rotavirus (mRV) infection. Neonatal homeostatic IFN-λ responses independent microbiota pervasively distributed among IECs, distinguishing them from the adult mice. Developmental differences in IFN-stimulated signatures intestine...

10.1016/j.celrep.2025.115243 article EN cc-by-nc Cell Reports 2025-02-01

In Brief Patients with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection give rise to SARS-CoV-2 environmental contamination during childbirth.

10.1097/aog.0000000000004112 article EN cc-by-nc-nd Obstetrics and Gynecology 2020-08-19

Abstract Available information on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission by small particle aerosols continues to evolve rapidly. To assess the potential role of heating, ventilation, and air conditioning (HVAC) systems in airborne viral transmission, this study sought determine presence, if any, handling units a healthcare setting where Disease 2019 (COVID-19) patients were being treated. The presence SARS-CoV-2 RNA was detected approximately 25% samples...

10.1101/2020.06.26.20141085 preprint EN cc-by medRxiv (Cold Spring Harbor Laboratory) 2020-06-28

Abstract The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has dramatically transformed policies and practices surrounding public health. One such shift is the expanded emphasis on environmental surveillance for pathogens. Environmental methods have primarily relied upon wastewater indoor surface testing, despite substantial evidence that SARS-CoV-2 commonly travels through space in aerosols, there been limited air surveillance. This study investigated...

10.1101/2021.03.26.21254416 preprint EN cc-by-nc-nd medRxiv (Cold Spring Harbor Laboratory) 2021-03-26

Abstract The three types of IFN have roles in antimicrobial immunity and inflammation that must be properly balanced to maintain tissue homeostasis. For example, IFNs are elevated the context inflammatory bowel disease may synergize with cytokines such as TNF-α promote damage. Prior studies suggest mouse intestinal epithelial cells (IECs), type III preferentially produced during viral infections less cytotoxic than I IFN. In this study, we generated human IEC organoid lines from biopsies...

10.4049/immunohorizons.2200025 article EN cc-by ImmunoHorizons 2022-07-01

Affordable and effective antiviral therapies are needed worldwide, especially against agents such as dengue virus that endemic in underserved regions. Many compounds have been studied cultured cells but unsuitable for clinical applications due to pharmacokinetic profiles, side effects, or inconsistent efficacy across serotypes. Such tool can, however, aid identifying clinically useful treatments. Here, computational screening (Rapid Overlay of Chemical Structures) was used identify entries...

10.1128/mbio.02839-20 article EN mBio 2020-11-09

Abstract Intestinal epithelial cell (IEC) responses to interferon (IFN) favor antiviral defense with minimal cytotoxicity, but IEC-specific factors that regulate these remain poorly understood. Interferon regulatory (IRFs) are a family of nine related transcription factors, and IRF6 is preferentially expressed by cells, its roles in IEC immunity unknown. In this study, CRISPR screens found Irf6 deficiency enhanced IFN-stimulated transformed mouse IECs not macrophages. Furthermore, KO...

10.1101/2024.01.04.574257 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2024-01-05

Tolerance of enteric microbiota and clearance potential pathogens is critical for gut homeostasis. We previously found that the healthy small intestine mice contains discrete pockets antiviral gene expression depend on bacterial colonization interferon lambda (IFN-λ) receptor by intestinal epithelial cells. now use spatial transcriptomic profiling homeostatic response to show they contain a broader cytokine signature consistent with activation innate immune sensors, including toll-like...

10.1080/19490976.2024.2447830 article EN cc-by Gut Microbes 2024-12-30

Abstract Interferon-lambda (IFN-λ) protects intestinal epithelial cells (IECs) from enteric viruses by inducing expression of antiviral IFN-stimulated genes (ISGs). Here, we find that bacterial microbiota stimulate a homeostatic ISG signature in the intestine specific pathogen-free mice. This is restricted to IECs, depends on IEC-intrinsic IFN-λ receptor ( Ifnlr1 ), and associated with production leukocytes. Strikingly, imaging these ISGs reveals localization pockets epithelium concentration...

10.1101/2021.06.02.446828 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2021-06-02
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