Defining the Role of Lymphatics in Pancreatitis Pathogenesis 

Beatriz Sosa-Pineda, PhD, professor of Medicine in the Division of Nephrology and Hypertension, received a 2.9 million dollar grant to study the role of lymphatics in pancreatitis, which could shed light on the mechanisms to treat other inflammatory diseases. The funding supports her project which seeks to elucidate cellular and molecular mechanisms that drive lymphatic remodeling in pancreatitis.  

What are the aims of the project?  

Pancreatitis is a prevalent and severe inflammatory disease of the pancreas with substantial clinical impact and limited treatment options. There is increasing evidence that the lymphatic vasculature is a critical regulator of inflammation and tissue repair in many organs. Lymphatics drain extravasated fluids, inflammatory mediators and immune cells. Moreover, in various inflammatory diseases, disruption of lymphatic expansion and remodeling — known as lymphangiogenesis — worsens inflammation and disease outcomes. Thus far, the role of lymphatic vessels in pancreatitis remains largely unexplored. We propose that understanding and improving lymphatic function may offer a new therapeutic approach to reduce disease severity and improve outcomes for patients with pancreatitis. The central goal of the study is demonstrating that lymphatics actively promote immune cell resolution and tissue repair during acute pancreatitis through VEGFR3/VEGF-C promoted lymphangiogenesis. 

What are your next steps? 

Building on exciting preliminary results from my laboratory, we will combine mouse models, pharmacologic tools, single-cell RNA sequencing, advanced imaging and bioinformatics to define the functional role of lymphatics in acute pancreatitis and to elucidate the cellular and molecular mechanisms that drive lymphatic remodeling in this disease.  

What do you hope will come out of this funded research? 

I hope to demonstrate that lymphatic vessels are critical regulators of pancreatitis pathophysiology. Additionally, I expect uncovering novel mechanisms linking lymphatic biology to pancreatic inflammation, immune resolution and fibrosis, will open a new avenue of investigation with direct relevance to patients with acute pancreatitis. Given the growing recognition of lymphatic dysfunction in diverse inflammatory diseases, the proposed studies are highly innovative and poised to have a substantial impact on the field.   

Learn more about the project here.