image: Dr. Lishomwa Ndhlovu
Credit: Weill Cornell Medicine
Weill Cornell Medicine has received a $5.2 million, initial two-year award from the Advanced Research Projects Agency for Health (ARPA-H) Lymphatic Imaging, Genomics, and pHenotyping Technologies (LIGHT) program to develop a comprehensive and innovative approach to diagnosing lymphatic disease. LIGHT is led by ARPA-H Program Manager Kimberley Steele, M.D., Ph.D.
The lymphatic system is a network of vessels, nodes and organs that drains excess fluid from tissues, filtering out waste and supporting the immune system by producing, activating and transporting infection-fighting cells. When the system is not working properly, fluid accumulates in tissues, a condition called lymphedema, and the body can become more susceptible to infection and tissue damage. However, diagnosis of lymphatic disease is challenging because the vessels are tiny and translucent and the fluid they carry moves slowly, which makes the system difficult to image.
The ARPA-H award funds a project called LANTERN (Lymphatic disease Advancements with Nanotechnology, Translational Epigenetics, and Research in Genetics), led by principal investigator Dr. Lishomwa Ndhlovu, the Herbert J. and Ann L. Siegel Distinguished Professor of Medicine in the Division of Infectious Diseases at Weill Cornell Medicine. LANTERN aims to improve the detection and understanding of lymphatic disease by developing new diagnostic tools. Researchers will use approaches such as large-scale analysis of genetic information, nanotechnology to create molecular fingerprints of the condition, and artificial intelligence to assess data. Early and precise detection of the condition can ultimately lead to better treatment.
“The goal of this program is really trying to make the invisible visible with technology that complements ongoing developments in imaging,” said Dr. Ndhlovu, who is also a professor of immunology in neuroscience at the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.
What is Lymphatic Disease?
Primary and secondary lymphatic disease affect hundreds of millions of people worldwide, according to the Lymphatic Education and Research Network. Primary lymphatic disease occurs when a person is born with abnormalities in their lymphatic vessels or nodes. Secondary lymphatic disease can occur from infection, chronic disease, trauma, surgery or cancer treatments like radiation. Lymphedema is one of the most common lymphatic diseases.
A better understanding of the lymphatic system is important because many chronic diseases have a lymphatic component, but physicians lack reliable tools to assess the lymphatic system, said Dr. Ndhlovu. Symptoms of lymphatic dysfunction, like swelling, often appear only after the disease has progressed. As a result, underlying chronic conditions can go untreated.
Creating a Diagnostic Toolbox
Dr. Ndhlovu and his colleagues aim to develop a diagnostic toolbox or platform that doctors can use to rapidly and reliably detect lymphatic disease. The toolbox would include biomarkers that provide information about the structure and function of the lymphatic system, the detection of genetic changes and epigenetic changes—or how environmental factors and behaviors alter how genes work—combined with other data.
The team includes collaborators Dr. Daniel Heller, a member of the Molecular Pharmacology Program at Memorial Sloan Kettering Cancer Center (MSK) and a professor in the Weill Cornell Graduate School of Medical Sciences and Dr. Mijin Kim, an assistant professor at Georgia Tech, who are developing advanced detection technologies using nanosensors, or tiny devices that can detect molecular changes in tissues, and artificial intelligence, to analyze information so that doctors can better predict and prevent disease and develop targeted treatment plans.
With collaborators Dr. Babak Mehrara, a plastic and reconstructive surgeon at MSK and professor of surgery (plastic surgery) at Weill Cornell Medicine, and Dr. Stanley G. Rockson, chief of consultative cardiology and the Allan and Tina Neill Professor of Lymphatic Research and Medicine at Stanford Medicine, the researchers will analyze information from existing patient databases as well as lymphatic fluid samples from patients at MSK and Stanford.
Another important part of the program is gathering input from patient advocates who can provide feedback on what types of information is valuable to them and their well-being.
At one point, Dr. Ndhlovu hopes to integrate the new platform with any new imaging modalities of lymphatic disease that researchers develop through the ARPA-H LIGHT program.
“I'm very excited about this opportunity,” Dr. Ndhlovu said. “This field has been a dark hole regarding imaging and diagnostics. The scope of diseases that are impacted by the lymphatic system is remarkable, so any advances in our understanding of lymphatic disease could have an impact across the spectrum of conditions including in our work in infectious diseases research.”