Ph.D., Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 1978
Stem cells give rise to all the diverse types of cells that make up our bodies. As we age, neural stem cells in the brain are lost, leading to age-related cognitive decline. I study the signals that control how neural stem cells decide when to divide and what to become, in an effort to understand age-related memory loss and depression.
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.
Encinas, J.M., Michurina,T.V., Peunova, N., Tordo, J., Peterson, D.A., Fishell, G., Koulakov, A., and Enikolopov, G. 2011. Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8: 566-579.
Méndez-Ferrer, S., Michurina, T.V., Ferraro, F., Mazloom, A., MacArthur, B., Lira, S.A., Scadden, D.T., Ma’ayan, A., Enikolopov, G., and Frenette, P.S. 2010. Stem cell pairs, mesenchymal and haematopoietic, form a unique niche in the bone marrow. Nature 466: 829-834.
Gleiberman A.S., Michurina T., Encinas J.M., Roig J.L., Krasnov P., Balordi F., Fishell G., Rosenfeld M.G. and Enikolopov G. 2008. Genetic approaches identify adult pituitary stem cells. Proc. Natl. Acad. Sci. USA 105: 6332-6337.
Peunova N., Scheinker V., Ravi K. and Enikolopov G. 2007. Nitric oxide coordinates cell proliferation and cell movements during early development of Xenopus. Cell Cycle 6: 3132-3144.
Encinas J.M., Vaahtokari A. and Enikolopov G. 2006. Fluoxetine targets early progenitor cells in the adult brain. Proc. Natl. Acad. Sci. USA 103: 8233-8238.
Scientists uncover source of ovarian stem-like cells prone to give rise to ovarian cancer
Study identifies stem cell-related changes that may contribute to age-related cognitive decline
CSHL scientists identify elusive neuronal targets of deep brain stimulation
Researchers discover that one type of stem cell creates a niche for another type within bone marrow