Joshua B. Slee is a Ph.D. Candidate in the Cell and Molecular Biology program.
Joshua Slee came to Lehigh after earning a Bachelor of Science and a Master of Science in Biotechnology from Marywood University in Scranton, PA. During his time there, he studied exercise-induced asthma and investigated the harmful effects of automobile air pollution on airway function. This work sparked a desire to further understand how the inflammatory process can be harmful in other health disorders. He entered the doctoral program and joined the biochemistry lab of Linda Lowe-Krentz in the summer of 2008.
|top - Joshua Slee preparing cells for incubation
bottom - Slee explaining his research to new faculty member, Julie Miwa
The Lowe-Krentz lab is interested in determining the underlying molecular, cellular, and biochemical processes involved in the development of atherosclerosis (heart disease) and ways to attenuate the disease process. Of particular interest is the study of how blood flow (shear stress) relates to atherosclerosis. Normal shear stress has been shown to be anti-inflammatory and protect against the development of atherosclerosis. A second focus of the lab is to understand the mechanism of action for heparin in the vasculature. Heparin is well-known for its role as an anti-coagulant and also has potential for use as an anti-inflammatory agent in atherosclerotic vasculature.
The lab has published data showing that shear stress in the vasculature mediates whole cell, actin microfilament, and nuclei realignment in the direction of shear stress. These cellular changes have been shown by others to protect against the development of atherosclerosis. Heparin treatment of vascular smooth muscle cells in culture has been shown by the Lowe-Krentz lab as well as others to slow cell proliferation, a hallmark of atherosclerotic vascular smooth muscle cells. The lab has data to support the involvement of a cell surface receptor and downstream signaling involving protein kinase G (PKG) and mitogen-activated protein kinase phosphatase-1 (MKP-1). Independent of PKG and MKP-1 signaling, heparin treatment has also been shown to promote inactivation of Erk, a major player in promoting cellular proliferation.
Josh’s dissertation work has focused on identifying proteins involved in mediating the anti-inflammatory effects of shear stress and identifying a receptor for heparin. He has published his work showing that the actin binding protein, cofilin, is involved in facilitating shear stress responses. He has demonstrated that cofilin facilitates proper actin turnover and barrier maintenance in vascular endothelial cells and that these effects are in part regulated through stress kinases, JNK and p38. This project was initiated when Josh worked as the graduate student mentor for the HHMI Biosystems Dynamics Summer Institute summer project in 2008. He is currently conducting experiments to support biochemical data suggesting that the heparin receptor might be a previously uncharacterized transmembrane protein. Josh is employing a combination of cellular, molecular, and biochemical techniques to attack this project from all sides. Identification of the heparin receptor would allow for future research to develop the therapeutic potential of heparin in the treatment of vascular diseases.
When not working on his dissertation, Josh enjoys teaching and guest lecturing in the core biology curriculum in the department and training students working the lab. He has designed and delivered lectures in cellular metabolism and cardiovascular disease physiology. Outside of teaching and working in the lab, Josh and his wife Kyle have a certified service and therapy dog named Tucker, who regularly visits nursing homes and special education classes.
Josh was the recipient of Lehigh’s Nemes Fellowship in the Fall of 2011. He is also a member of the Delta Epsilon Sigma and Kappa Gamma Pi national honors societies. His work has been presented at national conferences and published in peer-reviewed journals and books.
Dr. Lowe-Krentz's research is funded by a grant from the National Institutes of Health.