Office: R4 125
Mervin C. Yoder Jr, MD
Distinguished Professor, Indiana University
Richard and Pauline Klingler Professor
Professor of Biochemistry and Molecular Biology
Director, Herman B Wells Center for Pediatric Research
Vice-Chair for Basic Research, Department of Pediatrics
Associate Dean for Entrepreneurial Research Indiana University School of Medicine
Associate Director for Entrepreneurship Indiana Clinical and
Translational Sciences Institute
- B.A.: Malone College
- M.A: Indiana State University
- M.D.: Indiana University School of Medicine
- Pediatrics Residency: Children’s Hospital of Philadelphia
- Neonatal-Perinatal Medicine Fellowship: Children’s Hospital of Philadelphia
Current Research Interests:
The Yoder laboratory is focused on identifying the regulatory pathways modulating the cells that are involved in vascular formation, remodeling, and repair with a focus on understanding the process of vasculogenesis. Identification of circulating endothelial colony forming cells (ECFC) in human umbilical cord blood and adult peripheral blood has provided a new insight into one mechanism through which human blood vessels can be formed via postnatal vasculogenesis. In collaboration with Dr. David Ingram, we developed a clonal ECFC assay that permits elucidation of the intrinsic proliferative potential of an endothelial cell and has provided new insights into the heterogeneity of endothelial proliferative potential in a variety of human blood vessels and in the circulating cells of normal or aged subjects. We have also optimized an in vivo vasculogenic assay to measure the capacity of endothelial progenitor cells to form human blood vessels upon implantation in immunodeficient mice. We have also identified a cell isolation and identification protocol using specific monoclonal antibodies and polychromatic flow cytometric approaches for the circulating ECFC. We are now focusing on the therapeutic effects of these cells when implanted in immunodeficient animal models of acute renal failure, oxygen induced retinopathy, hyperoxic neonatal lung injury, and vascular ischemic injuries.
We are also examining the potential of reprogramming circulating blood cells from patients with peripheral arterial disease into induced pluripotent stem cells (iPS). We then direct the differentiation of the iPS cells into ECFC via specific progenitor stages. We have determined that the iPS- or hES-derived ECFC display many properties of cord blood ECFC including clonal proliferative potential, high telomerase activity, and in vivo vessel forming potential. In addition, the iPS-derived ECFC display the ability to prevent neovascular tufts and revascularize the avascular region of oxygen-induced retinopathy in newborn mice and rescue blood flow and limb recovery in mice with experimentally induced ischemic hindlimb injury. Our current protocol permits generation of the iPS-derived ECFC with high efficiency (1 iPS cell produces > 1X108 ECFC within 80 days). Further studies are identifying methods to enhance generation of the iPS-derived mesoderm subset that produces the ECFC precursors. We are developing protocols for the safe efficient generation of human ECFC.
A second long-term area of interest is in the study of the temporal and spatial origin of hematopoietic stem cells (HSC) and progenitors in the developing murine embryo. We have made seminal contributions in the field through the identification of the first long term repopulating cells to emerge within the yolk sac and embryo proper. Subsequently, we have demonstrated that essentially all of the definitive hematopoietic progenitor cells (EMP) that seed the fetal liver at E10 are derived from the yolk sac, with no contribution from the embryo proper. We have also reported that B1 B, marginal zone B cell progenitors, and T cells are derived autonomously in the yolk sac and embryo proper from hemogenic endothelial cells. Thus, the yolk sac possesses definitive hematopoietic and lymphopoietic activity that is independent of the embryo proper and occurs without an obvious stem cell precursor stage (a challenge to the stem cell theory of hematopoiesis). These results directly bear on assays used to identify HSC in vitro and in vivo as investigators focus on deriving HSC and progenitor cells from human iPSC and ESC. For example, in related work, we have discovered that mESC derived hemogenic endothelial cells give rise to EMP, B1a, B1b, and T cells in vitro and in vivo. Thus, the mESC are recapitulating emergence of HSC-independent lineages similar to yolk sac stages of blood cell development.