Ömer H. Yilmaz, MD, PhD

"The adult intestine is maintained by stem cells that require a cellular neighborhood, or niche, consisting in part of Paneth cells. By better understanding how intestinal stem cells and their Paneth cell niche adapt to diverse diets, we hope to identify and develop new strategies that prevent and reduce the growth of cancers involving the intestinal tract."

Ömer Yilmaz is the Eisen and Chang Career Development Professor, an Associate Professor of Biology at MIT, and a gastrointestinal pathologist at the Massachusetts General Hospital and Harvard Medical School. He is a graduate of the University of Michigan Medical School, where he performed his thesis work under the guidance of Professor Sean Morrison. He also spent two years as a visiting postdoctoral Fellow in the laboratory of Professor David M. Sabatini, a member of the Whitehead and Koch Institutes. He joined the faculty of the Koch Institute in 2014. Professor Yilmaz has been awarded a V Scholar Grant from the Jimmy V foundation and an American Federation for Aging Research Grant for Junior Faculty. In 2016, he was named a Sidney Kimmel Scholar, an honor granted to the nation's most promising young cancer researchers. Professor Yilmaz was also named a Pew-Stewart Scholar for Cancer Research, which is a national initiative designed to support innovative early career scientists whose research will accelerate discovery and advance progress to a cure for cancer.

Research Summary

The goal of the Yilmaz laboratory is to understand how adult stem cells and their microenvironment adapt to diverse diets in the contexts of tissue regeneration, aging, and cancer initiation. Accordingly, Professor Yilmaz is 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 into tissue-specific cell types, they likely play an important role in remodeling the intestine in response to diet-induced physiologies.

Most 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 cells' cellular neighborhood or “niche,” and elaborate myriad growth factors and cues necessary for the maintenance of ISCs. The Yilmaz lab is working to understand the molecular mechanisms underpinning the interactions between ISCs and Paneth cells in conditions of calorie restriction, and 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.

For more information about Professor Yilmaz’s research, please visit the Yilmaz lab webpage.

Selected Publications

Roper J, Tammela T, Cetinbas NM, Akkad A, Roghanian A, Rickelt S, Almeqdadi M, Wu K, Oberli MA, Sánchez-Rivera F, ... Yilmaz ÖH. 2017. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol 35: 569–576.

Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS, Helenius K, Park Y, Azimi R, Kerper NR, Wesselhoeft RA, et al. 2017. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature 545: 355–359.

Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, Bauer-Rowe KE, Xifaras ME, Akkad A, Arias E, Pinello L, Katz Y, Shinagare S, Abu-Remaileh M, Mihaylova MM, Lamming DW, Dogum R, Guo G, Bell GW, Selig M, Nielsen GP, Gupta N, Ferrone CR, Deshpande V, Yuan GC, Orkin SH, Sabatini DM, Yilmaz ÖH. 2016. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature 531: 53–58.

Yilmaz ÖH, Katajisto P, Lamming DW, Gültekin Y, Bauer-Rowe KE, Sengupta S, Birsoy K, Dursun A, Yilmaz VO, Selig M, Nielsen GP, Mino-Kenudson M, Zukerberg LR, Bhan AK, Deshpande V, Sabatini DM. 2012. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486: 490–495.

Oravecz-Wilson KI*, Philips ST*, Yilmaz ÖH*, Ames HM, Li L, Crawford BD, Gauvin AM, Lucas PC, Sitwala K, Downing JR, Morrison SJ, Ross TS. 2009. Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder. Cancer Cell 16: 137–148.

Yilmaz ÖH, Kiel MJ, Morrison SJ. 2006. SLAM family markers are conserved among hematopoietic stem cells from old and reconstituted mice and markedly increase their purity. Blood 107: 924–930.

Yilmaz ÖH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, Morrison SJ. 2006. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441: 475–482.

Kiel MJ*, Yilmaz ÖH*, Iwashita T*, Terhorst C, Morrison SJ. 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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