The question of fundamental interest to our laboratory is how cells maintain a quiescent, proliferative or differentiated state. Once a cell becomes specialized for function in a particular tissue, that differentiated state is stable, yet the molecular mechanisms that control the expression of its characteristic repertoire of genes are largely dynamic. Our research is directed at understanding this apparent paradox and elucidating the nature of cell memory and cell plasticity. By perturbing the intracellular or extracellular milieu, we are probing the regulatory network that determines cell fate and how it can be altered. This knowledge is key to our understanding of stem cell quiescence, self-renewal, differentiation, and how cancer arises. This information is also critical to the use of somatic cells or stem cells for therapeutic purposes.

Stem Cell Biology in Bioengineered Niches: we are using nanotechnology to study the role of extrinsic tethered and soluble factors in stem cell fate determination and self-renewal. Specifically, we are studying the effects over time of soluble components (growth factors, morphogens and cytokines) and tethered insoluble components (cell-cell adhesion and extracellular matrix components) on apoptosis, cell division, and differentiation of live single cells in hydrogel microwells by time lapse microscopy. We are elucidating the cell intrinsic molecular mechanisms that govern nuclear reprogramming critical to directing adult stem cell differentiation for use in cell based therapies. To study chromatin remodeling mechanisms necessary for reprogramming, we are using cell fusion and nuclear transfer approaches.

Technology Development for Elucidation of Regulatory Pathways: using technologies developed in our laboratory (restriction enzyme generated siRNAs (REGS) for loss of function analyses and beta-galactosidase assays of protein complementation for monitoring intracellular protein translocation, membrane receptor protein interactions, and non-invasive in vivo imaging, we are determining the molecular bases (chromatin remodeling and signaling pathways) for changing the nuclear function of embryonic and adult stem cells.

Other Recent Work: our laboratory has worked in a broad range of research disciplines in the past. Most recently, we have studied the RNAi pathway and angiogenesis. Members of our lab have developed a technology to generate shRNA libraries. In addition, we have helped to understand better how the RNA interference pathway operates. Angiogenesis is a critical component of stroke, head injury, vascular malformations, development and brain tumor growth to name a few. Recently we have found a means for enhancing VEGF's beneficial effects while abrogating its deleterious effects.

• Streetz KL, Doyonnas R, Grimm D, Jenkins DD, Fuess S, Perryman S, Lin J, Trautwein C, Shizuru J, Blau H, Sylvester KG, Kay MA "Hepatic parenchymal replacement in mice by transplanted allogeneic hepatocytes is facilitated by bone marrow transplantation and mediated by CD4 cells." Hepatology 2008; 47: 2: 706-18 More
• Pajcini KV, Pomerantz JH, Alkan O, Doyonnas R, Blau HM "Myoblasts and macrophages share molecular components that contribute to cell-cell fusion." J Cell Biol 2008; 180: 5: 1005-19 More
• Wehrman T, He X, Raab B, Dukipatti A, Blau H, Garcia KC "Structural and Mechanistic Insights into Nerve Growth Factor Interactions with the TrkA and p75 Receptors." Neuron 2007; 53: 1: 25-38 More
• Springer ML, Banfi A, Ye J, von Degenfeld G, Kraft PE, Saini SA, Kapasi NK, Blau HM "Localization of vascular response to VEGF is not dependent on heparin binding." FASEB J 2007; More
• Kutschka I, Chen IY, Kofidis T, von Degenfeld G, Sheikh AY, Hendry SL, Hoyt G, Pearl J, Blau HM, Gambhir SS, Robbins RC "In vivo optical bioluminescence imaging of collagen-supported cardiac cell grafts." J Heart Lung Transplant 2007; 26: 3: 273-80 More