Marie-Claude Hofmann
Associate Professor, Veterinary Biosciences
Professional Interests: Many
questions about the biology of stem cells remain unanswered. Some of
these are: what defines a stem cell, or "stemness," what is
the influence of the stem cell "niche" in regulating stem cell
self-renewal and differentiation, and what are the intracellular signaling
pathways underlying stem cell behavior. Answering these questions will
bring us closer to effectively engineer stem cells and tissues for regenerative
therapy, and provide new insights into the etiology of certain cancers.
My research program uses spermatogonial stem cells as a model to answer
these questions. These stem cells are pluripotent, giving rise to daughter
cells that belong to the three embryonic germ layers. We are particularly
interested in elucidating the molecular mechanisms that control spermatogonial
cell fate decision by the growth factor glial cell line-derived neurotrophic
factor (GDNF). We recently demonstrated that at least one pathway triggered
by GDNF involves the activation of Src family kinases and the up-regulation
of N-Myc. We are now investigating signaling networks that converge
onto N-Myc and probing its role for self-renewal/differentiation. Further,
we are conducting studies aimed at understanding the impact of possible
toxicants, such as certain nanomaterials, on the germ line and signaling
pathways in spermatogonial stem cells.
Selected Publications:
Braydich-Stolle L, Kostereva NV, Dym M, and Hofmann MC (2007). Role of Src kinases and N-Myc in spermatogonial stem cell proliferation. Dev Biol, In press .
Cooke PS, Hess RA, Simon L, Schlesser HN, Carnes K, Tyagi G, Hofmann MC and Murphy KM (2006). The transcription factor Ets-Related Molecule (ERM) is essential for spermatogonial stem cell maintenance and self-renewal. Animal Reproduction 3: 98-107.
Hess RA, Cooke PS, Hofmann MC, Murphy KM (2006). Mechanistic insights into the regulation of the spermatogonial stem cell niche. Cell Cycle 5:1164-70.
Braydich-Stolle L, Dym M and Hofmann MC (2005). Role of glial cell line-derived neurotrophic factor (GDNF) in germ-line stem cell fate. Ann. NY Acad. Sciences , 1061:94-?
Braydich-Stolle L, Hussain S, Schlager J and Hofmann MC (2005). In vitro cytotoxicity of nanoparticles in mammalian germ-line stem cells, Toxicol. Sci . 88: 412-419.
Chen C, Ouyang W, Grigura V, Zhou Q, Carnes K, Lim H, Zhao GQ, Arber S, Kurpios N, Murphy TL, Cheng AM, Hassell JA, Chandrashekar V, Hofmann MC, Hess RA, and Murphy KM (2005). ERM is required for the transcriptional control of the spermatogonial stem cell niche. Nature 436: 1030-1034.
Hofmann MC, Braydich-Stolle L, and Dym M (2005). Isolation of male germ line stem cells; influence of GDNF. Dev Biol 279: 114-24.
Hofmann MC, Braydich-Stolle L, Dettin
L, Johnson E, and Dym M (2005). Immortalization of mouse germ-line stem
cells. Stem Cells 23: 200-210 .
