Omer H. Yilmaz

"The adult intestine is maintained by stem cells that require a cellular neighborhood, or niche, consisting in part of Paneth cells. Our laboratory will investigate the molecular mechanisms of how intestinal stem cells and their Paneth cell niche respond to diverse diets to coordinate intestinal regeneration with organismal physiology and its impact on the formation and growth of intestinal cancers.  By better understanding how intestinal stem cells adapt to diverse diets, we hope to identify and develop new strategies that prevent and reduce the growth of cancers involving the intestinal tract that includes the small intestine, colon, and rectum."

The goal of the Yilmaz laboratory is to understand how adult stem cells and their microenvironment adapt to diverse diets in the context of tissue regeneration, aging, and cancer initiation. Towards this end, they are studying the effects of dietary interventions such as calorie restriction and high fat diet-induced obesity on intestinal stem cell (ISC) function in the mammalian intestine.  Since ISCs, like all adult stem cells, possess the ability to self-renew and the capacity for differentiating in tissue-specific cell types, they likely play an important role in remodeling the intestine in response to diet-induced physiologies.

A majority of ISCs express the G protein-coupled receptor 5 (Lgr5) and reside at the bottom of intestinal crypts nestled between Paneth cells. These cells constitute a component of the stem cell cellular neighborhood or “niche,” and elaborate myriad growth factors and cues necessary for the maintenance of ISCs. The Yilmaz lab is working on elucidating the molecular mechanisms underpinning the interaction between ISCs and Paneth cells in conditions of calorie restriction and will complement this by studying the response of this interaction in obesity. By comparing how ISCs adapt to diverse diets, they will gain a deeper understanding of how the intestine integrates physiology with its growth and why some diets reduce or increase the risk of colon cancer.

Birsoy K, Wang T, Possemato R, Yilmaz ÖH, Koch CE, Chen WW, Hutchins AW, Gultekin Y, Peterson TR, Carette JE, Brummelkamp TR, Clish CB, Sabatini DM. (2013) MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors. Nature Genetics 2013 Jan;45(1):104-8. PMCID: PMC3530647

Yilmaz, Ö.H.*, Katajisto, P.*, Lamming, D.W., Gültekin, Y., Bauer-Rowe, K.E., Sengupta, S., Birsoy, K., Durun, A., Yilmaz, V.O., Selig, M., Nielsen, G.P., Mino-Kenudson, M., Zukerberg, L.R, Bhan, A.K., Deshpande, V., and Sabatini, D.M. (2012) mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486, 490-5. PMCID: PMC3387287

Lee, J.Y., Nakada, D., Yilmaz, Ö.H., Tothova, Z., Lim, M.S., Gilliland, D.G., Morrison, S.J. (2010) An mTOR-induced tumor suppressor response contributes to the depletion of hematopoietic stem cells after Pten deletion. Cell Stem Cell 7(5), 593-605. PMCID: PMC2995996

Oravecz-Wilson, K.I.*, Philips S.T.*, Yilmaz, Ö.H.*, Li, L., Lucas, P.C., Sitwala, K., Downing, J.R., Morrison, S.J., Ross, T.S. (2009) Persistence of Leukemia-initiating Cells in a Novel Mouse Model of Imantinib-Responsive Myeloid Leukemia. Cancer Cell 16(2): 137-148. PMCID: PMC2763369

Levi, B., Yilmaz, Ö.H., Duester, G and Morrison, S.J. (2009) Aldehyde dehydrogenase 1a1 is dispensable for murine nervous and hematopoietic stem cell function. Blood 113(8), 1670-1680. PMCID: PMC2763369

Kiel, M.J., Yilmaz, Ö.H., and Morrison, S.J. (2008) CD150 negative cells are transiently reconstituting multipotent progenitors with little or no stem cell activity. Blood 111(8), 4413-4414. PMCID: PMC2293285

Yilmaz, Ö.H. and Morrison, S.J. (2008) The PI-3kinase pathway in hematopoietic stem cells and leukemia-initiating cells: a mechanistic difference between normal and cancer stem cells. Blood Cells Mol Dis. 41(1), 73-76. PMCID:  PMC2517145

Yilmaz, Ö.H., Valdez, R., Thiesen, B.K., Guo, W. Ferguson, D.O., Wu, H., and Morrison, S.J. (2006) Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475-482. [Cover Article].

Yilmaz, Ö.H., Kiel, M.J., and Morrison, S.J. (2006) SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity. Blood 107, 924-930.

Kiel, M.J.*, Yilmaz, Ö.H.*, Iwashita, T.*, Terhorst, C., and Morrison, S.J. (2005). SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells. Cell 121, 1109-1121.

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