image: Jerome Breslin, USF Health
Credit: USF Health
A team of University of South Florida investigators led by Jerome Breslin, professor of Molecular Pharmacology and Physiology in the USF Health Morsani College of Medicine, has received $3.3 million in federal funding for an innovative program that could help identify the role dysfunction in the lymphatic system plays in a wide range of diseases.
The funding represents the first award given to USF Health by the Advanced Research Projects Agency for Health. The ARPA-H program is named LIGHT -- Lymphatic Imaging, Genomics, and pHenotyping Technologies -- and led by ARPA-H Program Manager Kimberley Steele, M.D.
The USF project is only the fourth ARPA-H project to be funded in Florida and the first within the state university system. USF’s project is one of 11 awards that ARPA-H announced Tuesday. Other awardees include Columbia University, Stanford University, the University of Pennsylvania and Weill Cornell Medicine.
The goal of LIGHT is to make “the invisible lymphatic system visible,” according to the program’s webpage, through developing new techniques for medical imaging, identifying new biomarkers and identifying genomic variants that can be used to diagnose lymphatic dysfunction.
“This is a two-year project, and the whole idea behind an ARPA is to get things to market as soon as possible,” Breslin said. “It is very different than a National Institutes of Health grant. We check in with our program manager almost weekly and have monthly status report meetings. And there’s actually someone who is assigned to us from ARPA-H to help guide us through the process, with the whole idea of getting research from the bench to market expeditiously.”
Though not visible to the naked eye, the lymphatic system plays a major role in the healthy function of all major organs. The problem to be addressed, Breslin explained, is that while there is a growing appreciation for the contribution of lymphatic dysfunction to disease, ways to identify lymphatic problems are severely limited.
Patients with primary lymphatic disease are often misdiagnosed, leading to inappropriate treatments and prolonged progression of swelling of limbs, causing disfigurement and disability. In addition, difficulty in assessing lymphatic health impairs understanding of its role in a variety of common, chronic diseases. Cancer, obesity, heart failure, inflammatory bowel disease, chronic kidney and liver diseases, autoimmune disorders and neurodegenerative diseases all have lymphatic components.
That’s where USF’s work on LIGHT comes in.
“The program has three arms or track areas — diagnosis and monitoring through biomarker discovery; imaging technologies; and prevention, prediction and diagnostic confirmation,” Breslin said. “Probably the most important of the three is imaging. Currently there is no way to image things like lymph flow in real time, at least more than once in the same person. The current technology is very rudimentary.”
While the circulatory system pumps blood continuously through the body, the lymphatic system plays a different role.
“It’s more of a drainage system, because the circulatory system is constantly leaking out a little bit of water to give to all the tissues and cells, as well as proteins and nutrients.” Breslin said. “The lymphatic system essentially serves like the drains to pick up all that water in the tissues that’s left over and bring it back into the circulatory system.”
When the lymphatic system malfunctions, however, the fluids from the circulatory system that bathe the cells build up and pressure in the system increases, causing potentially dangerous issues with swelling. The challenge is that lymphatic vessels are tiny and translucent, making them much harder to see than blood vessels. Lymph fluid moves through them at a slow rate and low pressure, preventing many of the diagnostic techniques used for veins and arteries from being effective. Lymph fluid itself is also highly variable in composition.
If successful, LIGHT will not only illuminate the unseen aspects of the lymphatic system through novel diagnostic approaches but also significantly improve patient care and outcomes by gaining a deeper understanding of its critical role in health.
A key purpose of the project is to build a new database that enables the direct connection between an individual’s genome, the landscape of gene expression at the mRNA level in individual cell types; the protein expression profile at the tissue level, to better map how the normal lymphatic system should work; and direct functional analysis of the individual’s lymphatic vessel function.
The value of such a database, Breslin said, is that it can be used to create a computer-based simulation model that will lay the foundation for new analytical tools to decipher the mechanisms underpinning lymphatic dysfunction. This model will enable new analysis approaches to discover biomarkers of lymphatic-related diseases and determine potential therapeutic targets to improve lymphatic dysfunction.
In addition to being a collaboration between the USF Health Morsani College of Medicine and the USF College of Public Health, LIGHT also has partnered with the USF Bellini College of Artificial Intelligence, Cybersecurity and Computing because Breslin’s team is working on advancing a new AI approach to analyze data.
“The Technology Transfer office is also heavily involved in the project to help bring advances into the commercial sphere so that the new discoveries can be made available for future patient care,” Breslin said.
A unique feature of the ARPA-H award is the pairing of an early-career scientist with an advocate from the patient community, dubbed the Discovery Duo. The pair will serve to engage stakeholders who may benefit from the new technology, and to increase awareness of lymphatic diseases among medical professionals. The Discovery Duo will hold meetings with at least 50 stakeholders in the next two years to gather and disseminate information, serving as a bridge between the research team and community.
Other key members of the USF research team include: Mengmeng Chang, M.D.; Laurelis Santiago; Michele Tyrpak and Christine Meister.