Our group studies the role of the cell microenvironment in development of healthy and diseased tissues for applications in regenerative medicine and cancer therapeutics. In particular, we focus on cell-cell interactions, soluble signaling and development of biomaterials to control cell behavior. Our efforts are focused on three main areas: 1) In vivo capture of metastatic cells, 2) Cellular dormancy and activation, and 3) Transport across physiological barriers.
In Vivo Capture of Metastatic Cells: A major challenge in cancer treatment is the inability to effectively prevent or treat metastasis of the cancer from the site of origin to other organs. We design biomaterial scaffolds that can be used to capture and destroy metastatic cells for various types of cancer.
Cellular Dormancy and Activation: Throughout the body there are stem cell populations that help maintain tissue homeostasis. These cells typically remain in a dormant state until injury or growth requires their activation to repopulate cells within the tissue. Disseminated cancer cells can also remain dormant at various sites in the body for years before reactivating and causing recurrence of metastatic disease. We aim to understand the mechanisms that control the switch between cellular quiescence and activation, which could have broad implications in translational applications such as mobilizing endogenous stem cells for regenerative therapies and inducing dormancy of disseminated tumor cells to prevent disease recurrence.
Transport Across Physiological Barriers: There are various cellular barriers throughout the body that regulate physiological transport, including the blood-brain barrier, the intestinal epithelial barrier, and skin. Our goal is to use stem cell-based models of these barriers in order to study transport across these barriers in healthy and diseased tissues.
- Baxter Young Investigator Award, 2013
- National Science Foundation Graduate Research Fellowship, 2007-2010
- Ronald A. Ragatz Outstanding Teaching Assistant Award, 2008
- Interdisciplinary Stem Cell Fellowship, UW-Madison Regenerative Medicine and Stem Cell Cluster, 2007
- Azarin S.M., Yi J., Gower R.M., Aguado B.A., Sullivan M.E., Goodman A.G., Jiang E.J., Rao S.S., Ren Y., Tucker S.K., Backman V., Jeruss J.S., and She L.D. "In vivo capture and label-free detection of early metastatic cells." Nat. Communic. 6, 8094 (2015).
- Lian X., Zhang J., Azarin S.M., Zhu K., Hazeltine L.B., Bao X., Hsiao C., Kamp T.J., and Palecek S.P. “Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/Î2-catenin signaling under fully defined conditions.” Nat. Protoc. 8, 162-175 (2013).
- Lippmann E.S.*, Azarin S.M.*, Kay J.E., Nessler R.A., Wilson H.K., Palecek S.P., and Shusta E.V. “Human blood-brain barrier endothelial cells derived from pluripotent stem cells.” Nat. Biotechnol. 30, 783-791 (2012). (*Equal contributions)
- Lian X., Hsiao C., Wilson G., Zhu K., Hazeltine L.B., Azarin S.M., Raval K.K., Zhang J., Kamp T.J., and Palecek S.P. “Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling.” Proc. Natl. Acad. Sci USA. 109, E1848-57 (2012).
- Azarin S.M., Larson E.A., Almodovar J.M., de Pablo J.J., and Palecek S.P. “Effects of 3-D microwell culture on growth and metabolism of human embryonic stem cells.” Biotechnol. Appl. Biochem. 59, 88-96 (2012).
- Azarin S.M., Lian X., Larson E.A., Mielke H.M., de Pablo J.J., and Palecek S.P. “Modulation of Wnt/Î2-catenin signaling in human embryonic stem cells using a 3-D microwell array.” Biomaterials. 33, 2041-2049 (2012).
- Broderick A.H., Azarin S.M., Buck M.E., Palecek S.P., and Lynn D.M. “Fabrication and selective functionalization of amine-reactive polymer multilayers on topographically patterned microwell cell culture arrays.” Biomacromolecules. 12, 1998-2007 (2011).
- Azarin S.M., and Palecek S.P. “Development of scalable culture systems for human embryonic stem cells.” Biochem. Eng. J. 48, 378-384 (2010).
- Mohr J.C., Zhang J., Azarin S.M., Soerens A.G., de Pablo J.J., Thomson J.A., Lyons G.E., Palecek S.P., and Kamp T.J. “The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells.” Biomaterials. 31, 1885-1893 (2010).
- Metallo C.M., Azarin S.M., Moses L.E., Ji L., de Pablo J.J., and Palecek S.P. “Human embryonic stem cell-derived keratinocytes exhibit an epidermal transcription program and undergo epithelial morphogenesis in engineered tissue constructs.” Tissue Eng. Part A. 16, 213-223 (2010).
- Wood K.C., Azarin S.M., Arap W., Pasqualini R., Langer R., and Hammond P.T. “Tumor-targeted gene delivery using molecularly engineered hybrid polymers functionalized with a tumor- homing peptide.” Bioconjug. Chem. 19, 403-405 (2008).