The Leung Lab

Research

Mucosal-associated invariant T (MAIT) cells as target for mucosal vaccine adjuvants.

MAIT cells are innate-like T cells that represent 1-10% of circulating T cells in humans and are abundant in mucosal tissues. We have profiled their activity in blood, duodenal, and skin tissue during cholera, sepsis, and burn injury, and have ongoing projects examining their transcriptional regulation and potential for use in cancer and sepsis immunotherapy. We have also reported on the capacity of MAIT cells to participate in B cell help, identifying a novel subset of MAIT cells that are enriched in human tonsil germinal centers possessing markers of follicular helper T cells (published in Science Immunology), and using animal and organoid models to examine the potential for harnessing MAIT cells as an adjuvant in mucosal vaccination. We have also worked on increasing our understanding of the function and regulation of MAIT cells in the context of sepsis and cancer.

Check out this recent publication!

Cheng OJ, Ryan EK, Bennett M, Clutter C, Cacioppo JG, Aubé J, Hogan AE, Leung DT. Signal Transducer and Activator of Transcription (STAT) Proteins Regulate Mucosal-Associated Invariant T (MAIT) Cell Function. Immunology. 2026 May;178(1):97-108.

Estimating Disease Burden with Cross-sectional Immunologic Data

Population estimates of incidence for diarrheal diseases such as cholera are limited by variability in access to healthcare, non-medically attended (including asymptomatic) cases, and limited sensitivity of tests based on microbial detection. Sero-surveillance, or the detection and quantification of pathogen-specific antibodies in a population sample, can be used to estimate exposure to pathogens. I have worked with multi-national teams to develop and implement novel methods for sero-epidemiological use for cholera surveillance. We have developed novel analytic methods using machine learning for cross-sectional interpretation of serology data (published in
Science Translational Medicine), and developed and optimized laboratory methods for use in sero-epidemiological investigations. We have past and current collaborations on cholera sero-surveillance with groups in Bangladesh, Cameroon, DRC, Haiti, and Vietnam.
 
Check out our recent publication!
 
 

Clinical decision support tools for management of diarrheal illness

Management decisions for diarrheal illness are often empiric, with laboratory testing not available or too costly. We have used machine learning approaches on data from large studies of pediatric diarrhea in both high- and low-income settings to develop and prospectively validate clinical prediction models for the diagnosis and prognosis of pediatric diarrhea. We have developed novel Bayes-informed methods for integrating environmental (climate and seasonality), epidemiological (background prevalence), and clinical parameters into a predictive model.  Alongside our data science work, we have conducted qualitative studies (interviews, focus groups) to inform the design of a decision-support tool for physicians in LMIC settings. We used this information to design a probability-based smartphone App for real-time decision-support that has been evaluated in a multi-site randomized cross-over trial in Mali and Bangladesh (published in JAMA Pediatrics). As an extension of this work, we have received NIH funding to examine the feasibility and acceptability of adapting such a decision-support tool for informal practitioners, such as Village Doctors in Bangladesh.

We currently have two active grants that are working towards this goal.

Through the first award (R21-R33), our research team, in collaboration with investigators from the International Center for Diarrhoeal Disease Research, Bangladesh (icddrb,b), is adapting a previously developed electronic clinical decision support tool (eCDST) into a comprehensive mHealth application. The tool is designed to support rural healthcare providers in the management of pediatric diarrhea.

Explore our recent publications to learn more!

Biswas D, Watt MH, Mangadu A, Das JB, Munim MS, Shihab RM, Khan ZH, Amin MA, Khan II, Islam MT, Hanson OR, Nelson EJ, Qadri F, Leung DT, Khan AI. Antibiotic dispensing behaviors for pediatric diarrhea: A qualitative study of informal healthcare providers in rural Bangladesh. PLoS One. 2025; doi.org/10.1371/journal.pone.0339283.

Khan ZH, Hanson OR, Amin MA, Biswas D, Islam MT, Nelson EJ, Mangadu A, Qadri F, Watt MH, Leung DT, Khan AI. Physicians’ Perspectives Regarding Informal Health Practitioners in Bangladesh. The American Journal of Tropical Medicine and Hygiene. 2025; doi.org/10.4269/ajtmh.24-0597.

Khan II, Hanson OR, Khan ZH, Amin MA, Biswas D, Das JB, Munim MS, Shihab RM, Islam MT, Mangadu A, Nelson EJ, Ahmed SM, Qadri F, Watt MH, Leung DT, Khan AI. Potential for an Electronic Clinical Decision Support Tool to Support Appropriate Antibiotic Use for Pediatric Diarrhea Among Village Doctors in Bangladesh. J of Pediatric Infectious Diseases Society. 2024; doi:10.1093/jpids/piae094.

 

The second grant (R01) focuses on the use of an eCDST to improve clinical decision-making for pediatric diarrheal illness. Our research team is collaborating with investigators across three study sites (Utah, Bangladesh, and Mali) to evaluate the feasibility and potential utility of an eCDST for improving diarrheal etiology prediction.

Explore our recent publications to learn more!

Dallas SA, Mangadu A, Das JB, Hanson OR, Khan ZH, Amin MA, Khan II, Islam MT, Biswas D, Munim MS, Shihab RM, Alam AN, Shirin T, Qadri F, Putnam J, Nelson EJ, Leung DT, Khan AI, Watt MH. Parents’ expectations for the management of pediatric diarrhea in the clinical setting: perspectives of parents and physicians in Bangladesh. Journal of Tropical Pediatrics. 2025; doi.org/10.1093/tropej/fmaf044.

Jones A, Mangadu A, Dallas S, Hanson OR, Arn K, Gesteland P, Szymczak JE, Pavia AT, Leung DT, Watt MH. Parent and Clinician Perspectives on Diagnostic Testing for Children With Diarrhea.JAMA Network Open. 2025; doi/10.1001/jamanetworkopen.2025.31000.

Murray JL, Leung DT, Hanson OR, Ahmed SM, Pavia AT, Khan AI, Szymczak JE, Vaughn VM, Patel PK, Biswas D, Watt MH. Drivers of inappropriate use of antimicrobials in South Asia: A systematic review of qualitative literature. PLOS Global Public Health. 2024 Apr 4;4(4):e0002507.

Immune responses to commensal organisms in early life

The development and role of the microbiota in young children has been well-characterized. Less is known about how the early childhood immune system interacts with non-pathogenic (“commensal”) organisms, and the role that these immune responses play in health and disease. We are using flow cytometry paired with next generation sequencing methods to examine the development and impact of antibody responses to the microbiota in cohorts of children.

Microbiome and antimicrobial resistance (AMR) in travelers

The global spread of AMR is increasingly attributed to human mobility, but historically, there was a lack of longitudinal cohort data with gene- and strain-level resolution to explain how short-term exposures drive acquisition and persistence of resistance. We were among the first groups to use shotgun metagenomic sequencing to show that international travel is associated with shifts in gut microbiome structure and resistome (AMR) composition (Langelier 2019). We then partnered with investigators at MGH/Broad to enroll a larger cohort of travelers, using similar methods as in our initial study, to show the acquisition and loss of AMR genes and strain-level changes in bacteria from fecal samples. These results provided evidence that travel can rapidly reshape microbial ecology and resistance carriage within individuals, and that risk can persist beyond the travel window. We are now examining the mechanisms by which the microbiome and resistome changes during travel.

Respiratory immune dysregulation following intestinal infection

The human intestinal and respiratory tracts share a common mucosal immune system. Infections of the intestine and respiratory tracts are the two most common infections occurring in children in low-resource settings. Very little is known of how an intestinal infection may affect the immunity and health of the respiratory tract. We are examining how lung immune responses changes during an intestinal infection, and if susceptibility to pneumonia challenge is affected. Our goal is to determine whether (and how) intestinal infections affect the lung, and whether intervening on intestinal infections could help prevent respiratory health problems.

 

Check out our GitHub Repository here!

Our Research is funded by the following:

NIH/NIAID (R33HD109819,R01AI135114, R21CA280224, K24AI166087, R21HD109819)
DOD/CDMRP (PRMRP Discovery Award W81XWH-17-1-0109)
Bill & Melinda Gates Foundation (OPP1198876, OPP1191944)

Laboratory of Daniel Leung, M.D.

Department of Women’s+ and Children’s Health, University of British Columbia

Division of Infectious Diseases, University of Utah