News

The summer has flown by and among the highlights were several lab potlucks. The photos above don’t do it justice, but our team has some amazing cooking skills. Reasons for our gatherings included: 1) the receipt of institutional training grants by our PhD students Owen and Daniel, 2) welcoming our summer intern, Andrew, who is part of the NARI (Native American Summer Research Internship) program, 3) Farewells to Taliman and Melanie, and 4) Birthdays of Shubhi, Olivia, Daniel, and Owen. We’re looking forward to more reasons to have potlucks this fall!

Last weekend was our annual lab Holiday Party, and we took the occasion to celebrate the recent accomplishments of a couple of our graduate students. Owen Jensen and Daniel Labuz, students in the Molecular Biology graduate program, passed their prelims! Owen’s thesis will be on, “Determining the role of mucosal-associated invariant T cells in mucosal adaptive immunity”, and Daniel will work on, “De novo DNA methylation of mucosal associated invariant T cells effector loci during sepsis.” We are glad that this (stressful) part is over with, and we are looking forward to seeing the results of their proposed studies!

As we mentioned in a previous post, recently at the ASTMH conference, we held a kickoff meeting for a project titled, “Development of a Bayesian diagnostic for etiological management of pediatric diarrhea.” This project is funded by the Bill & Melinda Gates Foundation, spearheaded by their Innovative Technology Solutions team. Our overarching goal is to develop and pilot a Smartphone App that will help clinicians in LMICs better manage kids with diarrhea. The “Bayesian” part is that this App would incorporate clinical, epidemiological, and environmental “priors”, such as climate data and clinical features of previous patients, into a clinical prediction App. For example, the App would ask the clinician to enter certain symptoms that the patient came with, computationally combine this information with cloud-based “priors” data (e.g. recent weather patterns, aggregate data from previous patients), and output the probability that a certain patient’s diarrhea is caused by a virus vs. bacteria. The clinician can then make a more informed decision about whether to give the patient an antibiotic or not. After we develop and validate the App, we will pilot it at two international sites. We are thankful for the expertise of our collaborators at Brown University, University of Florida, and University of Maryland, who are all part of this grant, as well as input from those at Institute for Disease Modeling and University of Virginia. In the end, we are really excited to have the opportunity to translate some of our current analytical efforts deriving prediction rules into an application that clinicians can use!

Last week, 5 members of our group attended the Annual Meeting of the ASTMH (American Society of Tropical Medicine and Hygiene) in New Orleans. We experienced some amazing Cajun food, street Jazz, and of course, the charms of the French Quarter. Some highlights from our group:

• Postdoc Shubhi Trivedi presented her work on respiratory immunity after intestinal infection
• Internal Medicine Resident Melissa Pender presented her work on clinical predictors differentiating causes of traveler’s diarrhea, a collaborative work with investigators at AFRIMS (Thailand) and CIWEC (Nepal)
• Tai Diep, our collaborator at the Pasteur Institut in Ho Chi Minh City, presented our work on use of dried blood spots in cholera serosurveillance.
• We kicked off our “Bayesian Diagnostics for Pediatric Diarrhea” project in a meeting with our funder (Bill and Melinda Gates Foundation) and collaborators (Brown University, University of Florida, University of Maryland)

Cole’s going away party (great to have significant others participating)

Michael’s going away potluck (who knew that our lab has such awesome cooks!)

Over the summer, we’ve had a couple of bittersweet parties, where we celebrated achievements, welcomed new PhD students, and sent off two of our lab members. Michael Graves is leaving us to attend medical school in Iowa, and Cole Anderson is leaving to take a scientist position in the military. We share their excitement about their new positions, but are sad to see them go.

We welcomed several new faces. Owen Jensen and Daniel Labuz are joining us as PhD students in the Molecular Biology program. Our new postdocs are Taliman Afroz (she had completed her PhD on E. coli sugar utilization pathways in Chase Beisel’s lab at NC State), and Ben Brintz (he completed his PhD on N-Mixture Models in Lisa Madsen’s group at Oregon State).

We also celebrated the start of a couple of R01 grants that we received from the NIAID: “Estimating cholera burden with cross-sectional immunologic data,” and “Development of clinical decision tools for management of diarrhea of children in high and low resource settings.”

Last week, we went out to Asian Tao to celebrate a few of our team’s recent achievements:

1) We received an R01 award, a 5-year grant from the NIH/NIAID. We will be working in collaboration with scientists at the icddr,b in Dhaka, Bangladesh to examine the role of MAIT cells (our favorite innate-like T cell) in the generation of antibody responses during cholera infection and vaccination. We are trying to address the problem that currently available oral cholera vaccines don’t work as well in young children as in older children and adults, which is likely related to the inability to generate polysaccharide-specific antibody responses in this population. Based on our earlier studies (in PLOS Neglected Tropical Diseases and Mike’s paper detailed below), we postulate that MAIT cells may provide help to B cells to generate such responses.

2) Cole, our postdoc, received a 2-year spot on the T32 in Genomic Medicine training grant from the NIH/NHGRI. In collaboration with the Rondina lab at the University of Utah, he will focus on the epigenetic and transcriptional events that occur in MAIT cells during the course of human sepsis.

3) Mike, our former postdoc who is now a R&D scientist at ARUP, had his paper published in the Journal of Leukocyte Biology. In this publication co-authored with Shubhi and Anita, Mike showed in a series of ex vivo experiments that human MAIT cells have the capacity to help B cells differentiate and produce antibodies.

4) Boris, our undergraduate student majoring in material science engineering, received an Undergraduate Research Opportunities Program (UROP) award. He will spend this semester working on a project titled, “Effect of HIV infection on Mucosal Associated Invariant T (MAIT) Cell Plasticity.”

Congratulations to everyone for their achievements!

Congratulations to Anita Iyer, PhD, postdoctoral fellow in our lab, who has been selected to receive an ASTMH (American Society of Tropical Medicine and Hygiene) Annual Meeting Award, supported in part by the Bill & Melinda Gates Foundation. She will receive funding to attend the conference, held November 13-17 in Atlanta, to present her research on immune responses to oral cholera vaccine in internally displaced persons in South Sudan.

Congratulations to our Undergraduate Research Opportunities Program (UROP) recipients for their poster presentations at recent research conferences! Joe Fuell presented a poster on “Immune Response to Native American Antidiarrheals” at the Utah Conference on Undergraduate Research in February (left photo), and Amanda Barrett presented a poster on “Use of Stool Immune Transcriptome to Predict Recurrent Clostridium difficile Infection” at the University of Utah Undergraduate Symposium last week (right photo).

The Leung lab has been awarded a grant from the University of Utah’s Center for Clinical and Translational Science and Program in Personalized Health to identify biomarkers for refractory Clostridium difficile infection.

Clostridium difficile infection (CDI) is the most common hospital-associated infection, responsible for an estimated 14,000 deaths a year in the US. While there are established antibiotic treatment regimens for CDI, up to 25% of treated cases relapse or recur. In collaboration with investigators from ARUP Laboratories and Intermountain Healthcare, we will be using cutting-edge genomic techniques to identify those who are at risk of developing recurrence of disease.

Announcement and details of other recipients here: http://healthcare.utah.edu/publicaffairs/news/2015/06/06-30-15_Precision_Medicine_Grants_Announcement.php
 

Congratulations to our 3 University of Utah Undergraduate Research Opportunities Program (UROP) grantees! Amanda, Joe, and Mait all received summer stipends to work on their research projects in our lab.

	Amanda Barrett The purpose of my UROP project is to determine if there are transcriptomic predictors for patients with recurrent Clostridium difficile infection (CDI). From stool samples, we will isolate host mRNA and analyze gene expression using RNA sequencing and qPCR. Both types of analysis should aid in comparing genes of interest and compare results between patients with recurring CDI, cured CDI, and a control group.
	Joseph Fuell Hundreds of years before the arrival of Western Medicine to the Salt Lake valley Native American tribes used local herbs to treat digestive problems such as diarrhea, stomach pains, and other intestinal problems.  My project consists of testing various roots and seeds used by Native Americans such as Rosa Woodsi, Grindelia Squarossa, Rumex crispus and Rhus trilobata.  These compounds are being tested for toxicity and activity on human intestinal and immune cells.
	Maitland Wiren The purpose of my UROP project is to study the activation of mucosal-associated invariant T (MAIT) cells. It is already known that some riboflavin metabolites activate MAIT cells. I will test to see if molecules produced by other types of disease-causing bacteria activate MAIT cells in a similar way. The overall goal is to get a better understanding of how diarrhea-causing bacteria affect our immune system.