Perelman School of Medicine at the University of Pennsylvania

Kahn Lab

Rotation Projects:

1. Signaling in cerebral cavernous malformation

Cerebral cavernous malformation (CCM) is a cerebral vascular disease that affects 200,000 individuals in the US.  It is both an inherited disease and an acquired disease, in both cases resulting from loss of the CCM protein complex in brain endothelial cells.  The lab has identified increased MEKK3-KLF2/4 signaling, ADAMTS5/versican, and other pathways as the basis for this disease.  Rotation projects are available to investigate how these and other signaling mechanisms contribute to CCM lesion formation using both mouse models and human patients.

2. Fluid shear forces in cardiovascular development and disease:  

An intrinsic aspect of the heart and vasculature is that their function is linked to physical forces associated with the movement of blood or lymph.  Fluid forces are believed to play central roles in the development of the heart, blood vessels and even lymphatic vessels, but the molecular and cellular pathways by which they do so have remained mysterious.  The lab is presently investigating a number of endothelial signaling pathways that are responsible for valve development and vascular development and remodeling in the blood and lymphatic systems.  These studies combine ex vivo flow chambers to study primary endothelial cells and mouse models to study vessel development and function in vivo.  Rotation projects are presently available to study the role of KLF2 signaling in response to fluid shear during valve development and novel links between hemodynamic forces and vascular diseases in the arterial and venous system.

3. Lymphatic vascular development and biology: 

Although largely forgotten for almost a century, the lymphatic vascular system is essential for many aspects of vertebrate life and a major player in many human diseases, including both cardiovascular disease and cancer. Our lab investigates a number of signaling pathways and cellular responses essential for lymphatic vascular development and function, including specialized signaling pathways (VEGF-C/VEGFR3) by which lymphatic vessels grow.  Rotation projects are presently available in both of these areas and in the new area of organ-specific lymphatic function using mouse genetic models and endothelial cell studies.

4. Placenta vascular development: 

The placenta is critical for proper embryonic development, however how the placenta forms is not well understood. Both maternal and fetal contributions to the placenta are required for proper placental function. To this end, our lab has created novel genetic mouse models to study how the placenta develops. Rotation projects are available using our novel tools to investigate placenta biology.

5. COVID-19: 

COVID-19 is associated with many vascular and non-pulmonary pathologies. Many of the mechanisms of COVID-19 multi-organ dysfunction are not well understood. This has important implications for treating both acute COVID-19 disease and Long COVID (chronic disease). Rotation projects are presently available in investigating how COVID-19 spreads and causes lethal disease.