Dr. Hanna Mikkola's group is interested in the development of hematopoietic stem cells (HSC). Their goal is to identify members of the transcriptional regulatory network that controls HSC development and function. As many of these regulators are involved both in normal blood cell development and in hematopoietic malignancies, understanding how these molecules work will also unravel the regulatory mechanisms that are disturbed in leukemias. Another line of their research focuses on studying the fetal hematopoietic microenvironments that nurture developing HSCs. As the main limitation hindering improvement of HSC therapies is the inability to maintain the self-renewal capacity and pluripotency of HSCs in culture, understanding how these programs develop in the embryo will be instrumental for learning how to expand cord blood or bone marrow HSCs, or even to generate HSCs from human embryonic stem cells, ultimately developing better cure for leukemia and other blood cell disorders.
Selected Cancer-Related Publications:
Chhabra A, Lechner AJ, Ueno M, Acharya A, Van Handel B, Wang Y, Iruela-Arispe ML, Tallquist MD, Mikkola HK. Trophoblasts regulate the placental hematopoietic niche through PDGF-B signaling. Dev Cell. 2012 Mar 13;22(3):651-9. Epub 2012 Mar 1
Van Handel B, Prashad SL, Hassanzadeh-Kiabi N, Huang A, Magnusson M, Atanassova B, Chen A, Hamalainen EI, Mikkola HK. The first trimester human placenta is a site for terminal maturation of primitive erythroid cells. Blood. 2010 Oct 28;116(17):3321-30. Epub 2010 Jul 13
Rhodes KE, Gekas C, Wang Y, Lux CT, Francis CS, Chan DN, Conway S, Orkin SH, Yoder MC, Mikkola HK. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell. 2008 Mar 6;2(3):252-63.
Schenke-Layland K, Angelis E, Rhodes KE, Heydarkhan-Hagvall S, Mikkola HK, Maclellan WR. Collagen IV induces trophoectoderm differentiation of mouse embryonic stem cells. Stem Cells. 2007; 25(6): 1529-38.
Teitell MA, Mikkola HK. Transcriptional activators, repressors, and epigenetic modifiers controlling hematopoietic stem cell development. Pediatr Res. 2006; 59(4 Pt 2): 33R-9R.