Alexander M. Simon, PhD

Personal Information
Associate Professor of Physiology
(520) 621-9778
amsimon@email.arizona.edu

Alex M. Simon, PhD, is the principal investigator on NIH grant R21HL122443, studying the role of Connexin47 mutations in primary lymphedema, a potentially debilitating disorder of the lymphatic system in which interstitial fluid abnormally accumulates and is estimated to affect as many as 140-250 million people worldwide. Valves in lymphatic vessels normally ensure that lymph moves forward rather than moving in the wrong direction and abnormally collecting in tissues. The goal of this project is to explore the idea that some forms of primary lymphedema are caused by defective valve formation resulting from mutations in Connexin genes.  Connexins are a family of related proteins which assemble into gap junction intercellular channels, structures that allow for the direct transfer of small molecules between adjacent cells.

Dr. Simon’s lab has discovered that three Connexins (Cx37, Cx43, and Cx47) are expressed in the endothelial cells of developing lymphatic vessels and that these proteins become progressively enriched at lymphatic valves. Using mouse genetic models, Cx37 and Cx43 were shown to be critical for lymphatic valve formation. Work in other labs has shown that Cx47 is mutated in some families with primary lymphedema, but nothing is known about the role of Cx47 in lymphatic development or function.  In the current research, the effects of Cx47 mutations on lymphatic valve formation, lymphatic function, and development of lymphedema will be assessed in mice. In addition, the effects of combined mutations of Cx47 and Cx43 will be determined as a test of the idea that both Cx47 and Cx43 must be inhibited for severe lymphatic disease symptoms, including lymphedema.