Explore This Lab

Overview

The goal of the Yilmaz laboratory is to understand how diverse diets influence the regeneration and development of cancers in the intestine. Although diet is known to impact the regeneration of the intestine and the incidence of intestinal cancers, very little is understood about the cellular and molecular mechanisms that underlie these processes. The intestine is a rapidly proliferating organ that on average replaces its entire lining every 5 days, which in an average adult human equates to approximately 300 grams of new intestinal tissue being generated daily. Intestinal stem cells power this regeneration by undergoing either self-renewal divisions that generate more stem cells or a series of divisions that engender the various differentiated cell types of the adult intestine.

To function properly, intestinal stem cells also require support cells, or niche cells, consisting of Paneth cells that play a key role in modulating stem cell function in response to calorie intake. By integrating cues from their Paneth cell niche, intestinal stem cells remodel the composition and function of the intestine, allowing for the intestine to dynamically adapt to different diets. Since stem cells and their niche drive intestinal regeneration in response to  diet and because most cancers are understood to arise from transformed or mutated stem cells, it is likely that intestinal stem cells, diet, and cancer are interconnected. The Yilmaz lab is working on elucidating the molecular mechanisms underpinning this connection between stem cells, diet, and cancer in conditions of low calorie diets as well as in high fat diet-induced obesity. By better understanding how intestinal stem cells adapt to diverse diets, his lab hopes 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.

Publications

Mihaylova M, Cheng CW, Cao AQ, Tripathi S, Mana MD, Bauer-Rowe KE, Abu-Remailleh M, Clavin L, Erdemir A, Lewis C, Freinkman E, Huang Y, Bell G, Deshpande V, Carmeliet P, Katajisto P, Sabatini DM, Yilmaz ÖH.
Fasting-Activated Fatty Acid Oxidation Enhances Intestinal Stem Cell Function. Cell Stem Cell. 2018; 22(5):769-778.

Roper J, Tammela T, Akkad A, Almeqdadi M, Santos, SB, Jacks T, Yilmaz ÖH. Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation. Nature Protocols. 2018;13(2):217-234.

Roper J, Tammela T, Cetinbas NM, Akkad A, Roghanian A, Rickelt S, Almeqdadi M, Wu K, Oberli M, Sánchez-Rivera FJ, Park Y, Liang X, Eng G, Azimi R, Kedrin D, Neupane R, Beyaz S, Sicinska ET, Bass A, Suarez Y, Yoo J, Chen L, Taylor MS, Zukerberg L, Katajisto P, Tsichlis PN, Lees J, Deshpande V, Chen J, Hynes RO, Langer R, Bhutkar A, Jacks T, Yilmaz ÖH. Epithelial genome editing and organoid transplantation models of
colorectal cancer. Nature Biotechnology. 2017; 35(6):569-576.

Beyaz S, Mana MD, Roper J, Kedrin D, Saadatpour A, Hong SJ, Bauer-Rowe KE, Xifaras ME, Akkad A, Pinello L, Katz Y, Shinagare S, Abu-Remaileh M, Lamming D, Guo G, Selig M, Nielsen GP, Gupta N, Ferrone C, Deshpande V, Yuan GC, Orkin SH, Sabatini DM, Yilmaz ÖH. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016; 531(7592):53-8.