Henke Lab

The Henke Lab, led by Dr. Peter K. Henke, aims to better understand venous thrombosis and vein wall injury.

Current Research in the Henke Lab

Led by Dr. Peter K. Henke, the Leland Ira Doan Professor of Surgery, the Henke Lab investigates how blood clots in venous thrombosis (VT) resolve over time and how they damage the vein wall as they do. Dr. Henke's work as a vascular surgeon enables our laboratory to ask, and answer, important questions that impact patients' lives and outcomes following VT. Our lab has been funded since 2003 by the National Institutes of Health, the American Venous Forum and other organizations.

Our work is highly collaborative, with active partnerships within the Conrad Jobst Vascular Research Laboratories, the University community and externally. We conduct basic science and translational studies using small animal models and a range of physiological, immunological and molecular biological techniques. Our aim is to better understand how blood clots break down, how and why these processes often lead to vein wall damage and how we can prevent it.

The Problem

Venous thrombosis is responsible for significant morbidity and mortality each year in the United States and around the world. If not treated quickly enough, blood clots within the vessels can travel to the lungs, causing life-threatening pulmonary emboli. Treatment today includes anticoagulation agents, but these carry a risk of unwanted bleeding, and they don't protect the vein wall from injury. 

Even after a clot resolves, many patients — particularly those who suffer from recurrent VT — develop irreversible scarring in the vessel wall that leads to a host of problems, known as post-thrombotic syndrome (PTS). Causing pain, swelling and ulceration, PTS can severely impact patients' lives. Unfortunately, short of preventing another blood clot, no effective therapy exists to treat, or prevent, PTS.

The Approach

Our lab focuses on how the formation and breakdown of a clot leads to scarring and PTS. More specifically, we look at the mechanisms involved in damage to and protection of the vein wall. Our investigations explore the role of signaling molecules, or cytokines, as well as many types of immune cells and the processes associated with infection and inflammation.

The goal that spurs our research forward is to understand the basic mechanisms of VT resolution and the scarring we see in PTS. We do this in order to identify biomarkers to speed DVT diagnosis and provide new targets for safe, effective and preventive therapies for both DVT and PTS.

Contributions to Science

Over the past two decades, our work has advanced the understanding of how blood clots resolve and how the vessel wall responds to a thrombotic event. Notably, we have identified key pathways involved in the resulting scarring, or fibrosis, and provided several new insights into vein wall response following VT.

  • Our work has confirmed the inflammatory environment surrounding a clot and clarified how inflammatory signaling molecules and immune cells are involved — particularly at different stages of clot resolution — in animal models of VT.
  • We've found that whether a clot forms due to stasis or non-stasis impacts how much vein wall scarring occurs, as does the amount of time the clot is in contact with the wall. Clot size, however, does not seem to have as great an impact.
  • We have clarified signaling proteins involved in clot resolution and vein wall injury in the setting of inflammation, namely TLR-4 and 9. These findings point us to pathways other than those involved in coagulation, which helps us identify additional potential therapeutic approaches without the bleeding risk of current medications.
  • In addition, our laboratory has helped clarify the role of matrix metalloproteinases, a family of enzymes that break down extracellular tissue material within vessels. Our work has found that these enzymes are important both to VT resolution at certain points in time and to scarring in the vein wall.
  • We also have been leaders in developing and sharing guidelines for investigators for selecting and working with murine research models of VT.

Dr. Henke discusses the research being conducted in his laboratory.