In 2014, the Mayo Clinic and Illinois Alliance awarded seed funding to four collaborative research teams to address three grand challenges related to biomarker discovery. Two projects have reached their conclusion within the seed program, and the Mayo Clinic and Illinois investigators are now using the data generated to expand their research.
Challenge One: Detection of Biomolecules from Body Fluids for Early Detection of Disease
This challenge was taken on by a research team comprised of Dr. Patricio Escalante, from the Division of Pulmonary and Critical Care Medicine at Mayo Clinic; Yi Lu, professor of chemistry at Illinois; Rashid Bashir, Abel Bliss Professor and department head of bioengineering at Illinois; and Ryan Bailey, professor of chemistry at the University of Michigan (formerly Illinois). Their project, titled “Novel Biomarkers and Point-of-Care Methods for Latent Tuberculosis Infection” aims to develop point-of-care (POC) diagnostic technologies that detect immune biomarkers for high-risk latent tuberculosis infection (LTBI) in a variety of patient populations and settings, improve diagnosis of LTBI, and individualize patient management.
Tuberculosis is a bacterial infection caused by mycobacterium tuberculosis. According to the World Health Organization (WHO) in its 2016 Global Tuberculosis Report, one third of the world’s population is infected. In 2015 alone, 1.8 million people died from tuberculosis, and in the same year another 10.4 million new cases were estimated, worldwide. Add the complex tuberculosis lifecycle, specifically the reactivation of dormant or latent infection (LTBI), plus vaccine resistance—and fallout of epidemic proportions are possible. Currently, the mechanism of TBI reactivation is unknown, but reactivation from a latent infection is the most prevalent source of transmission. The WHO cites gaps in testing and reporting for TB as a major challenge of this top 10 global cause of death.
The Mayo Clinic and Illinois research group has been working to develop three POC device platforms for LTBI. The first is a POC multiplexed cytokine-chemokine detecting technology. The device uses a silicon photonic micro ring resonator (MRR) assay to detect various immune biomarkers in antigen-activated blood samples. This novel MRR technology has been clinically validated at the Mayo Clinic, and there is currently a manuscript in process detailing this work.
The second device in development utilizes personal glucose meters for POC diagnosis of LTBI. The investigators are in the processes of further validation of this technology. However, they believe this device has great potential for rapid diagnosis of LTBI in resource-limited settings.
The third technology is a POC microfluidics platform that has proven successful for other diagnostic applications, such as early sepsis detection, but is being improved upon to reach the level of detection needed for LTBI.
The Mayo Clinic and Illinois team intends to continue their work to further improve and validate all three LTBI diagnostic technologies. Currently, four papers detailing various pilot studies of these technologies are in the process of publication. Additionally, the group has several grant proposals in preparation to acquire external funding for their continued research and technology development.
Challenge Three: 3-D Cancer Tumor Chip-Avatars for Personalized Drug Therapy
Brendan Harley, associate professor of chemical and biomolecular engineering at Illinois, and Drs. Daniel Ma and Jann Sarkaria from the Department of Radiation Oncology at Mayo Clinic received seed funding to address this challenge. Their project, titled “Chip-based engineered tumor microenvironments for glioma therapy” demonstrated the use of engineered glioma biomaterials to find successful therapies for glioblastoma multiforme (GBM), which is the most common, aggressive, and deadly form of brain cancer and is often resistant to current therapeutic approaches.
The gelatin hydrogel platform developed by the Harley lab is proving to be a versatile tool for studying glioma progression, efficient evaluation of cell processes, and treatment efficacy. The platform can also be adapted to evaluate the response of patient derived samples, making this a promising technology for rapid assessment of personalized treatment strategies for GBM.
Prof. Harley, along with Dr. Sarkaria, Dr. Ian Parney, from the Department of Neurosurgery at Mayo Clinic, and Steven George, professor of biomedical engineering at Washington University in St. Louis, were recently awarded R01 funding from the National Cancer Institute, for their project titled “Biomimetic hydrogel niches to study the malignant phenotype of glioblastoma multiforme.” This award will allow the team to continue their work over the next five years.
This team of inter-institutional researchers has used the biomarker discovery seed program as a launching point to enhance and expand the degree, scope, and external funding potential of their collaborative interactions.
“We have established a pipeline for transferring patient derived xenograft cells with a wide variety of diagnostic and therapeutic trajectory information, gathered from more than 75 glioblastoma multiforme patients,” said Harley.
Additionally, Illinois professors Rohit Bhargava and H. Rex Gaskins have joined the project team. Several publications are in preparation and two NIH grants pending, in addition to the R01 award already received, to round out the research activity. To learn more about the continued glioma avatar project, visit the Harley lab website at harleylab.org.