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Our current research mostly centers on hematopoiesis and hematopoietic stem cells, and aging in these systems. Hematopoietic cells are responsible for constant maintenance and immune surveillance in almost every part of the body. As most blood cells have a relatively short lifespan, this requires the hematopoietic stem cell, the cell on top of the hematopoietic system, to have the greatest power of self-renewal of any adult tissue, along with cells in the skin.
Hematopoiesis is the process by which mature blood cells form from hematopoietic stem cells. Abnormal hematopoiesis and stem cell regulation are associated with a wide spectrum of diseases, ranging from anemia to cancer. Hematopoietic stem cells are also central to clinical cell therapy (i.e., stem cell transplantation and gene therapy).
In mice and humans there is a successive decline in stem cell function from adulthood to old age. This decline has been associated with perturbed tissue homeostasis and impaired injury repair in aged individuals. Hematopoietic stem cells (HSCs) from aged animals have limited ability to self-renew, to contribute efficiently to hematopoiesis and to differentiate into red blood cells and lymphoid cells. The mechanisms of HSC aging have remained largely unexplored.
Ryan MA, Nattamai KJ, Xing E, et al. Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization. Nat Med. 16:1141-1146. 2010.
Florian MC, Geiger H. Concise review: polarity in stem cells, disease, and aging. Stem Cells. 28:1623-1629. 2010.
Kalfa TA, Pushkaran S, Zhang X, et al. Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen. Haematologica. 95:27-35. 2010.
Chen X, Mitsutake N, LaPerle K, et al. Endogenous expression of Hras(G12V) induces developmental defects and neoplasms with copy number imbalances of the oncogene. Proc Natl Acad Sci USA. 106:7979-7984. 2009.
Geiger H, David S, Nattamai KJ, Jan V. Quantification of genomic mutations in murine hematopoietic cells. Methods Mol Biol. 506:423-436. 2009.
Geiger H, Rudolph KL. Aging in the lympho-hematopoietic stem cell compartment. Trends Immunol. 30:360-365. 2009.
Kohler A, Schmithorst V, Filippi MD, et al. Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones. Blood. 114:290-298. 2009.
Xu H, Eleswarapu S, Geiger H, et al. Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. Blood. 2009.
Bhatla D, Gerbing RB, Alonzo TA, et al. Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia. Br J Haematol. 2008.
Bhatla D, Gerbing RB, Alonzo TA, et al. DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group. Leukemia. 22:265-272. 2008.
Daria D, Filippi MD, Knudsen ES, et al. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood. 111:1894-1902. 2008.
Diwan A, Koesters AG, Capella D, Geiger H, Kalfa TA, Dorn GW, 2nd. Targeting erythroblast-specific apoptosis in experimental anemia. Apoptosis. 13:1022-1030. 2008.
Krejci O, Wunderlich M, Geiger H, et al. p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death. Blood. 111:2190-2199. 2008.
Milsom MD, Jerabek-Willemsen M, Harris CE, et al. Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells. Cancer Res. 68:6171-6180. 2008.
Weiss B, Geiger H, Davies SM. Possible leukemogenic potential of temozolomide. Pediatr Blood Cancer. 2008.
Williams JP, Wu J, Johansson G, et al. Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor that confers neurofibroma tumorigenic potential. Cell Stem Cell. 3:658-669. 2008.
Diwan A, Koesters AG, Odley AM, et al. Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis. Proc Natl Acad Sci USA. 104:6794-6799. 2007.
Dumble M, Moore L, Chambers SM, et al. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood. 109:1736-1742. 2007.
Geiger H, Koehler A, Gunzer M. Stem Cells, Aging, Niche, Adhesion and Cdc42: A Model for Changes in Cell-Cell Interactions and Hematopoietic Stem Cell Aging. Cell Cycle. 6. 2007.
Krejci O, Wunderlich M, Geiger H, et al. p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death. Blood. 2007.
Kustikova OS, Geiger H, Li Z, et al. Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathways. Blood. 109:1897-1907. 2007.
Li J, Sejas DP, Zhang X, et al. TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells. J Clin Invest. 117:3283-3295. 2007.
Liang Y, Jansen M, Aronow B, Geiger H, Van Zant G. The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice. Nat Genet. 39:178-188. 2007.
Yang L, Wang L, Geiger H, Cancelas JA, Mo J, Zheng Y. Rho GTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow. Proc Natl Acad Sci USA. 104:5091-5096. 2007.
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