ARPA-H awards up to $135.7M to illuminate the body’s hidden highway 

The LIGHT program taps the lymphatic system, a crucial but invisible network linked to rare and hidden diseases, cancer, and neurodegenerative diseases 

The Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services (HHS), today announced the research and development teams selected to carry out the Lymphatic Imaging, Genomics, and pHenotyping Technologies (LIGHT) program—a historic investment in lymphatics research of up to $135.7M over 5 years. These teams will develop the first comprehensive diagnostic toolkit to allow healthcare providers to detect problems with the lymphatic system earlier than existing methods, as part of a routine physical exam. 

Millions of Americans with lymphatic dysfunction—including an estimated 10 million living with lymphedema (extraordinary swelling around lymph nodes)—are misdiagnosed or never diagnosed at all. The consequences are profound: delayed or inappropriate treatment, preventable hospitalizations, missed days at work or school, disfigurement, disability, and even death. While imaging and genetic diagnostics for other organ systems have surged ahead, lymphatic diagnostics lag decades behind.  

“Lymphatic dysfunction quietly harms millions of Americans every year. Often, solutions are identified too late, if at all,” said HHS Deputy Secretary Jim O’Neill. ”This investment will help spur innovation to create efficient diagnostics that millions will benefit from. I look forward to the teams’ responses.” 

The ARPA-H LIGHT program is taking direct aim at one of medicine’s most glaring and long-standing blind spots. Despite being fundamental to our health—serving as the body’s drainage and filtration network, defending against infection, maintaining fluid balance, and supporting organ function—the lymphatic system has remained overlooked and under-studied.  

“The lymphatic system touches every major organ in your body, yet we’ve had no good way to see it, measure it, or understand when it’s failing,” said Alicia Jackson, Ph.D., ARPA-H Director. “Patients with lymphatic disease are misdiagnosed for years. And because we can’t see the system, we’re missing its role in the spread of cancer, heart failure, chronic inflammation, and neurodegenerative disorders. LIGHT will change that, transforming how we treat millions of Americans.”  

Lymphatic dysfunction is not limited to rare diseases. It is increasingly recognized as a major contributor to chronic conditions including diabetes, obesity, chronic kidney, liver, and lung diseases, and autoimmune and infectious diseases, such as Long COVID and Lyme disease. By enabling early, routine evaluation of lymphatic health, LIGHT aims to fundamentally change how these conditions are detected, monitored, and treated. If successful, LIGHT will give clinicians all over the country the tools needed to recognize lymphatic dysfunction earlier, personalize care, and prevent complications for patients who have never had access to this kind of specialized expertise.  

“Right now, most healthcare providers simply aren’t equipped—or trained—to recognize lymphatic dysfunction, and the tools they need are virtually nonexistent,” said LIGHT Program Manager Kimberley Steele, M.D., Ph.D. “Despite extraordinary advances in medical technology, we’re still relying on something as rudimentary as a tape measure to monitor changes in limb size—and even that lacks a standardized approach. These outdated methods reveal almost nothing about how the lymphatic system is actually functioning. As a result, countless patients are only diagnosed after their disease has advanced to a stage where reversing the damage is difficult or sometimes impossible. LIGHT will change this reality by bringing the lymphatic system out of the shadows and into the forefront of modern medicine.” 

The LIGHT program is involving the patient and caregiver perspective from the start. Each LIGHT performer team is required to include a Discovery Duo, unique pairing of an early-career investigator (JEDI: Jumpstarting Early-career Discovery and Innovation) and a patient or caregiver ambassador (BRIDGE: Beneficiary Representative Informing Development and Guiding Engagement). The Discovery Duo approach ensures that patient perspectives and real-world needs are integrated into the research and development process, a catalyst for user-centered innovation and supporting translation from bench to bedside. By uniting scientific rigor with lived experiences, this partnership illuminates unmet needs, builds credible solutions, and drives momentum toward market-ready advances in lymphatic medicine. 

Performer awards (not procurement contracts, grants, or cooperative agreements) vary in funding amount per awardee and are contingent upon each team meeting aggressive, milestone-driven goals.  

LIGHT’s performer teams are led by: 

• 3DT Holdings, LLC, in San Diego aims to develop a first-in-class interventional device to measure lymphatic flow and obstruction in real time, so clinicians can detect thoracic duct disease and related conditions, such as heart failure, earlier and more accurately, helping prevent years of misdiagnosis and serious complications. 
• Columbia University in New York City will use advanced cell-based and cell-free DNA panels to precisely diagnose and classify pediatric lymphatic anomalies, giving children and their families faster, clearer answers and more targeted, personalized care instead of years of uncertainty and trial-and-error treatment. 
• Hospital for Special Surgery in New York City aims to create the first-ever “GeneLoad” score to detect lymphatic dysfunction and predict an individual’s risk of developing lymphedema, including in patients with autoimmune disease, so high-risk patients can be identified and treated proactively before irreversible swelling and disability occur. 
• Stanford University in Calif. intends to transform magnetic resonance lymphangiography into a safer, faster, and more widely accessible imaging tool by reducing invasiveness, shortening scan times, improving resolution, and advancing contrast agents. This will allow more patients to receive comfortable, high-quality scans closer to home and get an earlier, more accurate diagnosis. 
• University of Alberta in Edmonton, Alberta, Canada, will build an innovative ultrasound and photoacoustic imaging system that can be used even in rural and resource-limited clinics to generate super-resolution, 3D views of lymphatic vessels and function, so patients in underserved areas can access advanced imaging without traveling long distances to specialized centers. 
• University of Arizona in Tucson seeks to develop phase change ultrasound lymphography with novel microbubble-based contrast agents optimized for lymphatic imaging, enabling rapid, point-of-care assessment of lymphatic function and detailed mapping of lymphatic networks at the bedside, so providers can make faster, more informed treatment decisions during a single visit. 
• University of California, Irvine, will optimize dual-energy contrast-enhanced CT lymphangiography as a practical, non-invasive, high-resolution method for quantifying lymphatic flow and detecting tissue-specific dysfunction, such as thoracic duct obstruction, making advanced lymphatic diagnosis feasible in community hospitals as well as specialty centers. 
• University of Pennsylvania in Philadelphia aims to deploy AI-driven multi-omics to discover biomarkers and targeted imaging agents for liver and gut lymphatics, addressing the lack of FDA-approved lymphatic-specific contrast agents and allowing earlier more precise detection of lymphatic involvement in liver and gastrointestinal disease to help prevent organ damage and improve long-term outcomes. 
• University of South Florida in Tampa intends to build an AI-powered predictive tool—a “clinical copilot” for lymphatic disease—to help providers diagnose, monitor, and treat lymphatic-related conditions with greater accuracy and personalization, so patients can benefit from expert-level decision support even when their clinician is not a lymphatic specialist. 
• Weill Cornell Medicine in New York City will develop a comprehensive diagnostic platform that integrates AI-enabled biomarker technologies, high-resolution photoacoustic imaging, and multimodal genetic-epigenetic predictors, giving clinicians the ability to detect lymphatic dysfunction much earlier in the disease process and opening a window for timely intervention before severe symptoms develop. 
• William Marsh Rice University in Houston, Texas, seeks to create a non-invasive photoacoustic imaging system with advanced near-infrared molecular probes and highly sensitive biomarker measurements to dramatically improve diagnosis and monitoring of rare and complex lymphatic diseases, so patients who have long struggled to get a clear diagnosis can be identified and followed more accurately, reducing the risk of sudden, life-altering complications. 

Learn more about LIGHT on its program page.