Manolis Roulis, Ph.D

Assistant Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Contact InformationStellar Chance Laboratories 505A (office) /515 (lab)
422 Curie Boulevard
Philadelphia, PA, 19104
Office: 215-573-9812


Specialty Division

Cancer and Immunobiology

Expertise Summary

Function and architecture of the mesenchymal microenvironment in tissue homeostasis, immunopathology and cancer

Research Expertise

Homeostasis in mucosal barrier tissues is maintained through complex interactions between resident cell types, the immune system and the microbiota. The overarching goal of my research is to understand why and how this balance is broken at the onset of chronic inflammatory, fibrotic and neoplastic processes, which may lead to an irreversible loss of tissue architecture and organ functionality. In this context, the mesenchymal microenvironment and its primary constituents, the extracellular matrix and the millions of fibroblasts that build it, is one of the most enigmatic areas of tissue biology today. The research of my laboratory focuses on the biology of recently discovered types of intestinal fibroblasts, which occupy specific niches within the tissue, have distinct transcriptional programs, but their function in physiology and in disease remains completely unknown. By integrating single cell studies in human tissues and in mice with functional analyses in mouse models, human organoids and organotypic systems, my laboratory aims to uncover specific cellular and molecular mechanisms through which fibroblasts control intestinal inflammation, fibrosis and tumorigenesis.

Graduate Groups

Cell and Molecular Biology


Diploma (Biology), National and Kapodistrian University of Athens, Greece, 2005
PhD (Immunology), BSRC “Alexander Fleming” and University of Ioannina, Greece, 2009

Specialty Certification

Postgraduate Training

Postdoctoral Researcher, BSRC “Alexander Fleming,” Athens, Greece, 2009-14
Associate Research Scientist, Department of Immunobiology, Yale School of Medicine, 2015-23

Awards and Honors

State Scholarships Foundation (IKY) Award, Greece, 2002
PENED PhD Scholarship, General Secretariat of Research and Technology, Greece, 2006-08
Travel Award, Weizmann Systems Biology Initiative, 2016
Career Development Award, Crohn’s and Colitis Foundation, 2017-20
Career Transition Award, Yale Cancer Center, 2021

Web Links

Selected Publications

Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions

Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner DF, Mehal WZ; AlcHepNet; Yuval Kluger, Flavell RA., Cell, 2023, PMID:37562401

Read article

MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche

Wu N, Sun H, Zhao X, Zhang Y, Tan J, Qi Y, Wang Q, Ng M, Liu Z, He L, Niu X, Chen L, Liu Z, Li HB, Zeng YA, Roulis M, Liu D, Cheng J, Zhou B, Ng LG, Zou D, Ye Y, Flavell RA, Ginhoux F, Su B., Nature 592(): 606-610, 2021, PMID:33658717

Read article

Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche

Roulis M, Kaklamanos A, Schernthanner M, Bielecki P, Zhao J, Kaffe E, Frommelt LS, Qu R, Knapp MS, Henriques A, Chalkidi N, Koliaraki V, Jiao J, Brewer JR, Bacher M, Blackburn HN, Zhao X, Breyer RM, Aidinis V, Jain D, Su B, Herschman HR, Kluger Y, Kollias G, Flavell RA., Nature 580(): 524–529, 2020, PMID:32322056

Read article

Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity

Jarret A, Jackson R, Duizer C, Healy ME, Zhao J, Rone JM, Bielecki P, Sefik E, Roulis M, Rice T, Sivanathan KN, Zhou T, Solis AG, Honcharova-Biletska H, Vélez K, Hartner S, Low JS, Qu R, de Zoete MR, Palm NW, Ring AM, Weber A, Moor AE, Kluger Y, Nowarski R, Flavell RA., Cell 180(1)(): 50-63, 2020, PMID:31923399

Read article

Host and microbiota interactions are critical for development of murine Crohn's-like ileitis

Roulis M, Bongers G, Armaka M, Salviano T, He Z, Singh A, Seidler U, Becker C, Demengeot J, Furtado GC, Lira SA, Kollias G., Mucosal Immunol, 2016, PMID:26487367

Read article

Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis

Roulis M, Nikolaou C, Kotsaki E, Kaffe E, Karagianni N, Koliaraki V, Salpea K, Ragoussis J, Aidinis V, Martini E, Becker C, Herschman HR, Vetrano S, Danese S, Kollias G., Proc Natl Acad Sci U S A 111(): E4658-67, 2014, PMID:25316791

Read article

Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology

Roulis M, Armaka M, Manoloukos M, Apostolaki M, Kollias G., Proc Natl Acad Sci U S A 108(): 5396-401, 2011, PMID:21402942

Read article

Search PubMed for articles