The research in my laboratory focuses on employing engineering fundamentals to study basic questions in vascular stem cell biology and applying these for tissue repair and regeneration and cancer impeding.

Vascular network formed from of ECFC (in green; nuclie in blue) embedded in Hyaluronic Acid hydrogels

Vascular network formed from of ECFC (in green; nuclie in blue) embedded in Hyaluronic Acid hydrogels

Polymeric hydrogels  

Hydrogels provide a highly controlled three-dimensional (3-D) environment that is structurally and biomechanically similar to native extracellular matrix (ECM) and can provide a rich biochemical landscape to influence cell behavior. These 3-D networks, formed by crosslinking polymers, are highly tunable biomaterials fabricated from a wide range of molecules using various synthesis methods to control cell behavior.

To understand and control vasculogenesis, we develop hydrogels to present ECM cues and study in vitro vascular morphogenesis of mature vascular cells or stem cell derivatives and in vivo angiogenesis of injured and diseased tissues.

Vascular differentiation and maturation

Stem cells aid the growth and repair of blood vessels. Human endothelial progenitors circulate in the bloodstream and can be endogenously triggered to home to injured or diseased sites such as ischemia or cancer to form vasculatures. Human pluripotent stem cells derived from the developing embryo or induced isolated from progenitors or mature cells, can differentiate into any cell type of the body. We study the induction and functionality of vascular cell derivatives from progenitor and pluripotent stem cells and their assembly into functional vascular networks.

Hypoxia

Variations in oxygen tension in the cellular microenvironment are common both in natural as well as engineered cell cultures, and such changes in oxygen level are known to regulate signaling cascades that lead to metabolic and phenotypic changes. We investigate the functional interactions between hypoxic (low oxygen) pathways and ECM-driven cues that are essential for vascular morphogenesis and network assembly.

Hypoxia regulation of ECM in endothelial progenitor and mature cells. [Taken from Kusuma  et al., FASEB J. 2012]

Hypoxia regulation of ECM in endothelial progenitor and mature cells. [Taken from Kusuma et al., FASEB J. 2012]