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From predicting the progression of kidney disease, to designing human-specific treatments for globally important infections like pneumonia, to developing novel tuberculosis therapies, to identifying new diagnostic tools and therapeutic options for patients with chronic liver disease, researchers at the Snyder Institute for Chronic Diseases are achieving new milestones that not long ago may have seemed distant and unattainable.

With help from the 2023 Canada Foundation for Innovation (CFI) John R. Evans Leaders Fund (JELF), four outstanding Snyder Institute members are moving their innovative research projects forward and tackling some of our greatest health-care challenges.

Kidney disease is a growing problem with no cure. A solid understanding of the molecular changes that occur in kidney disease is urgently needed, as a one-size-fits-all approach has had limited success. Chun’s precision medicine research program has a unique integration of human kidney tissue analysis and disease modelling with patient-derived kidney organoids.

“Support from CFI-JELF is making it possible for us to purchase state-of-the-art molecular technologies capable of detecting molecular changes at single cell resolution,” says Chun. “Understanding the molecular changes in kidney biopsies will help us to better diagnose and predict how disease will progress. Moreover, molecular spatial imaging can help develop new therapies and tailor treatments for individuals resulting in better health care and patient outcomes.” 

Molecular spatial imaging will allow Chun and his research team to visualize and quantify gene and protein expression at single cell resolution. This technology will facilitate a better understanding of the important genes that contribute to kidney diseases. Identification and validation of molecular targets in biopsies of patients with kidney disease will potentially lead to new therapies that can delay or treat kidney disease.

Chun is an assistant professor in the Department of Medicine at ��ݮ����Ƶ����’s Cumming School of Medicine, and a member of the Snyder Institute for Chronic Diseases. 

Gillrie’s research group is working to engineer human 3D tissues, or organs-on-chips, with functional blood vessels (vasculature) to understand how inflammation and infection impact organ-specific blood vessel function. Existing human tissue engineering models typically do not include blood vessels, which makes it impossible to understand how drugs, immune cells, and pathogens such as viruses or bacteria move in or out of tissues and affect organ function. This multidisciplinary team has designed models of lung and brain tissues with functioning 3D micro-vessels similar to those seen in human organs to study these processes.

“The CFI-JELF and matching Alberta Technology Innovation grants are critical to the success of our research team by providing microfluidic infrastructure within a dedicated advanced microscopy platform to fully integrate our organ-on-a-chip models,” says Gillrie.

“This funding will help us understand in real time how various infections cause blood vessel and tissue inflammation. It will also help us design human-specific treatments for inflamed blood vessels to treat globally important infections such as bacterial and viral pneumonia. Funding support for this type of research is vital. It advances medical discovery here in Calgary and beyond.”

Gillrie is an assistant professor of medicine in ��ݮ����Ƶ����’s Department of Microbiology, Immunology and Infectious Diseases, and Department of Medicine. He is an Infectious diseases clinician and member of the Snyder Institute for Chronic Diseases.

Khan and her research team investigate how Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), weakens immunity by impacting the bone marrow. TB is an ancient infectious disease of humans that has been extensively studied both clinically and experimentally. Unfortunately, there is not a single effective vaccine against TB, which indicates our limited understanding of host defense mechanisms against TB.

Khan’s proposed research will provide critical insights into how the bone marrow functions during stress, and will lead to the development of new therapies and/or vaccines to preserve/improve bone marrow function during infectious challenges. An additional objective of Khan’s research is to help clarify the role of the aged bone marrow microenvironment (BM niche) in blood cell production and its effect on the immunity of the elderly — populations that are highly vulnerable to infectious diseases, including TB.

According to a United Nations projection, the human population over the age of 60 will grow more than threefold during the first half of the 21st century and, by 2050, will exceed the size of the global population of young individuals. Unfortunately, antimicrobial resistance will become a significant problem in that time frame, and we’ve already experienced with the COVID pandemic the tragedy of how elderly populations can be disproportionately affected by infectious diseases. Therefore, targeted therapies for the elderly spurred by a greater understanding of their changing immune responses are highly warranted.

Khan will use a real-time cell metabolic analyzer and cell sorter to investigate the cellular constituent and molecular mechanisms involved in the communications between immune cells and the BM niche. By revealing the role of the BM niche in inducing hyperinflammation and immunopathology, new steps can be taken to better understand and combat the pathophysiology of infectious diseases.

“Immunometabolism is a growing field; thus, the CFI-JELF-funded infrastructure will help us establish a novel and independent research program that is only possible due to cutting-edge technology,” says Khan.

“Studying the metabolism of immune cells is a highly competitive research area that has gained significant interest on an international level. Therefore, this leading-edge research program will attract students and postdoctoral Fellows from within Canada and abroad, providing an internationally competitive training environment — and the CFI-JELF award will help us immensely with our research goals.”

Khan is an assistant professor in the Department of Microbiology, Immunology and Infectious Diseases, Department of Physiology and Pharmacology, and Department of Medicine at ��ݮ����Ƶ����’s Cumming School of Medicine. She is a member of the Snyder Institute for Chronic Diseases.

Nguyen’s research program — Precision Medicine in Hepatology — aims to identify new diagnostic tools and therapeutic options for patients with chronic liver disease. This research program spans the entire spectrum of fundamental/basic science to clinical translation, sometimes referred to as ‘bench-to-bedside.’

Nguyen’s research team performs mechanistic studies in animal models, uses molecular tools to interrogate human bio-banked samples, and evaluates patient outcomes in clinical trials. A major portfolio within this research program is focused on studying the impact of the gut-liver axis in non-alcoholic fatty liver eisease (NAFLD) — also known as metabolic dysfunction associated steatotic liver disease. In this portfolio, Nguyen aims to define avenues within the gut-liver axis by which microbiome alterations and the associated host immune and/or local tissue response can alter NAFLD outcomes for the better.

“We are extremely excited to be receiving the CFI-JELF award and will greatly benefit from it,” says Nguyen. “We plan to purchase a spectral flow cytometer that will expand the numbers and types of cells we are able to characterize in both our animal models and human studies. This will provide a more comprehensive assessment of the microbiome-dependent changes in the host that are occurring in the setting of NAFLD.

“Currently, both diagnostic tools to identify NAFLD patients with progressive liver disease and treatment options for these patients are limited. I am hopeful that the new spectral flow cytometer will provide additional insight that can bring us closer to addressing these unmet needs.”

Nguyen is an assistant professor of medicine in the departments of Medicine and MIID at ��ݮ����Ƶ����’s Cumming School of Medicine, and Liver Unit, Division of Gastroenterology and Hepatology. He is a member of the Snyder Institute for Chronic Diseases.