Arthur Mortha PhD
Assistant Professor
arthur mortha

Contact Info

T: (416) 978-6245

Location

St. George Campus
University of Toronto, Medical Sciences Building
1 King's College Circle, Room 7208
Toronto, ON, M5S1A8

Accepting

Grad Students Must First Apply Through Department
Postdoctoral Fellows
Undergraduate Students
Summer Students

Research Interests

Innate Immunity, Innate lymphoid cells, Mucosal Immunology, Mononuclear phagocytes

Research Interest:

1. Innate Lymphoid Cell (ILC) biology
The Mortha lab has a strong interest in understanding the biology of innate lymphocytes. ILCs are a new family of human and murine lymphocytes composing of at least 3 individual lineages (ILC1, ILC2 and ILC3). These cells are rare in our circulating blood, rare to moderately represented in lymphoid tissues but highly abundant at mucosal tissue sites (i.e. intestine, liver, lung, adipose tissue or skin). ILCs are tissue-resident cells, characterized by the lack of an antigen receptor, the expression of lineage-defining transcription factors (ILC1: Tbet, ILC2: Gata3 and ILC3: Rorc), the fast release of cytokines and their instructive communication with non-hematopoietic tissue cells (intestinal epithelial cells, hepatocytes, adipocytes and fibroblasts). ILCs play an important role in defining and tuning the activation state of the tissue in the steady state and during disease. They promote antimicrobial activity, tissue regeneration, metabolic activity and organogenesis and are thus key player in our body’s physiology. Our laboratory has several aims addressing key questions and problems in ILC biology:

  • We aim to identify tissue-specific determinants of ILC lineage commitment, function and plasticity.
  • We aim to generate ILC-specific transgenic tools using CRISPR/Cas9 technology.
  • We aim to design translational approaches targeting ILC-specific functions for therapy.
  • We aim to understand how ILCs control adaptive immunity in the steady state and during disease.

 

2. Host-microbiome interactions
A second research topic of the laboratory is the crosstalk of the host immune system and commensal microbiota. The commensal microbiota is an essential community of microbes composed of viruses, bacteria, fungi and protists settling on our body’s mucosal surfaces. The sum of all genes (metagenome) provided by our commensal flora allows us to access new metabolites, vitamins and proteins that are essential to healthy life. Preventing our immune system from attacking our commensal communities is thus a key target to maintain equilibrium. Mononuclear phagocytes (MNP) are sentinel cells of our body and directly and indirectly interacting with our microflora. While MNP are found at every mucosal surface of our body, the microbes they are interacting with are vastly different between those sites. The interactions and the location of the MNP within the tissue will determine the underlying immune response. We aim to understand the nature of these signals and the immunologic consequences underlying the encounter of microbial signals by MNP.

 

Publications and Awards

View PubMed search of this faculty member's recent publications.

Recent Publications

Selected publications:

A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GMCSF.
Chuang LS, Villaverde N, Hui KY, Mortha A, Rahman A, (…), Silverberg MS, Muise AM, Brant SR, Daly MJ, Segal AW, Duerr RH, Merad M, McGovern DP, Peter I, Cho JH.
Gastroenterology. 2016 Jul 1;

Neutrophil ageing is regulated by the microbiome.
Zhang D, Chen G, Manwani D, Mortha A, Xu C, Faith JJ, Burk RD, Kunisaki Y, Jang JE, Scheiermann C, Merad M, Frenette PS.
Nature. 2015 Sep 24;525(7570):528-32.

Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility.
Muller PA, Koscsó B, Rajani GM, Stevanovic K, Berres ML, Hashimoto D, Mortha A, Leboeuf M, Li XM, Mucida D, Stanley ER, Dahan S, Margolis KG, Gershon MD, Merad M, Bogunovic M.
Cell. 2014 Jul 17;158(2):300-13

Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.
Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP, Belkaid Y and Merad M,
Science. 2014 Mar 28;343(6178):1249288

Innate lymphoid cells integrate stromal and immune signals to enhance antibody production by splenic marginal zone B cells.
Magri G, Miyajima M, Bascones S, Mortha A, Puga I, Cassis L, Barra CM, Comerma L, Chudnovskiy A, Gentile M, Llige D, Cols M, Serrano S, Aróstegui JI, Juan M, Yagüe J, Merad M, Fagarasan S and Cerutti A,
Nat Immunol., 2014 Apr;15(4):354-64.

Regulated expression of nuclear receptor RORgt confers distinct functional fates to NK cell receptor-expressing RORgt(+) innate lymphocytes.
Vonarbourg C*, Mortha A*, Bui VL, Hernandez PP, Kiss EA, Hoyler T, Flach M, Bengsch B, Thimme R, Hölscher C, Hönig M, Pannicke U, Schwarz K, Ware CF, Finke D, Diefenbach A.
Immunity. 2010 Nov 24;33(5):736-51 *equal contribution

RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells.
Sanos SL, Bui VL*, Mortha A*, Oberle K, Heners C, Johner C, Diefenbach A.
Nat Immunol. 2009 Jan;10(1):83-91 *equal contribution

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