Dou, Diana (2012-2015)
Diana is in the Molecular Biology IDP. She joined the training program in 2012. Her research mentor is Dr. Hanna Mikkola. She received a B.S. degree in 2010 from CalTech. Diana has recently accepted an NSF Graduate Research Training Fellowship and is now an associate member of the CMB Training Program.
Mentor: Dr. Hanna Mikkola
Hematopoietic stem cells (HSCs) possess great clinical value in treating patients with diseases of the blood and immune system. HSCs are defined by their ability to self-renew and generate all lineages of the blood to reconstitute the hematopoietic system upon transplantation. However, limited quantities of HSCs from bone marrow donations and cord blood combined with the difficulty of matching donor HLA-types to recipients restrict availability of compatible cells suitable for treatment. Pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are another potential source of HSCs, but various molecular blocks prevent their differentiation into functional HSCs. Our lab has shown that ESC-derived hematopoietic stem/progenitor cells (HSPCs) display diminished proliferation potential, inability to differentiate the B-lymphoid lineage, and inability to engraft. We have identified the HOXA cluster and BCL11A genes as possible candidates contributing to these defects using a microarray. Our preliminary data have shown that knockdown of the HOXA and BCL11A genes in endogenous HSPCs is sufficient to recapitulate the defects observed in ESC-HSPCs. We are currently working to further elucidate the involvement of the HOXA and BCL11A genes in HSC development, including the use of ChIP-Seq to find genes these particular transcription factors may regulate. In the future, we will also test whether restoration of the HOXA and BCL11A genes in ESC-HSPCs is sufficient to overcome the self-renewal, B-cell differentiation, and engraftment defects. Identifying and overcoming the differences between endogenous and in vitro generated HSPCs will provide insight into the complex molecular interactions that are intricately entwined at specific developmental time points.
