Grigori Enikolopov and colleagues study stem cells in the adult brain. They have generated several models to account for how stem cells give rise to progenitors and, ultimately, to neurons, and they are using these models to determine the targets of antidepressant therapies, to identify signaling pathways that control generation of new neurons, and to search for neuronal and neuroendocrine circuits involved in mood regulation. Recent experiments suggest a new model of how stem cells are regulated in the adult brain, with a focus on stem cells’ decision on whether to divide—and embark on a path of differentiation—or remain quiescent. This model explains why the number of new neurons decreases with advancing age and may lead to impairments in memory and depressed mood. It also explains why multiple brain trauma and prolonged neurodegenerative disease may lead to accelerated decrease of cognitive abilities. In other research, the team has identified stem cell targets of various therapies used for treating depression and developed a general platform to determine the effect of drugs and therapies and predict their action. The team is now focusing on the signaling landscape of neural stem cells and on their interaction with the surrounding niche. Enikolopov’s group is also focusing on other types of stem cells in the organism. Their latest discovery, with a team at Cornell University, relates to a new type of stem cell in the ovary that normally heals the ovarian tissue after an oocyte is released, but easily transforms to become malignant and generate tumors. The team is now using these discoveries to reveal how stem cells relate to neural and oncological disorders.
Kulkarni, S. and Micci, M. A. and Leser, J. and Shin, C. and Tang, S. C. and Fu, Y. Y. and Liu, L. and Li, Q. and Saha, M. and Li, C. and Enikolopov, G. and Becker, L. and Rakhilin, N. and Anderson, M. and Shen, X. and Dong, X. and Butte, M. J. and Song, H. and Southard-Smith, E. M. and Kapur, R. P. and Bogunovic, M. and Pasricha, P. J. (2017) Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. Proc Natl Acad Sci U S A, 114(18) pp. E3709-E3718.
Licht, T. and Rothe, G. and Kreisel, T. and Wolf, B. and Benny, O. and Rooney, A. G. and Ffrench-Constant, C. and Enikolopov, G. and Keshet, E. (2016) VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis. Proc Natl Acad Sci U S A, 113(48) pp. E7828-E7836.
Koning, J. J. and Konijn, T. and Lakeman, K. A. and O'Toole, T. and Kenswil, K. J. and Raaijmakers, M. H. and Michurina, T. V. and Enikolopov, G. and Mebius, R. E. (2016) Nestin-Expressing Precursors Give Rise to Both Endothelial as well as Nonendothelial Lymph Node Stromal Cells. J Immunol, 197(7) pp. 2686-2694.
Mignone, J. and Peunova, N. and Enikolopov, G. (2016) Nestin-Based Reporter Transgenic Mouse Lines. Methods Mol Biol, 1453 pp. 7-14.
Saboor, F. and Reckmann, A. N. and Tomczyk, C. U. and Peters, D. M. and Weissmann, N. and Kaschtanow, A. and Schermuly, R. T. and Michurina, T. V. and Enikolopov, G. and Muller, D. and Mietens, A. and Middendorff, R. (2016) Nestin-expressing vascular wall cells drive development of pulmonary hypertension. Eur Respir J, 47(3) pp. 876-88.Additional materials of the author at
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