|Degrees:||PhD (VU University, Amsterdam, The Netherlands)|
|Phone:||613-520-2600 x 1209|
|Office:||3309 Health Sciences Building|
Primary Field of Specialization:
Mucosal Immunology and Epithelial (Stem Cell) Biology.
Mucosal tissue such as the digestive tract has several important basic functions including nutrient uptake. In addition, our gut serves to protect us from many challenges such as those induced by food or other damaging agents, as well as by pathogens. In our lab, we focus on the following three topics:
- Early-life gut development: Upon birth our guts are not fully developed yet, and massive changes still take place in the first year of life. In this timeframe, the commensal microbiota rapidly changes from pioneering species to a highly complex ecosystem, our major source of energy and nutrition switches from milk to solids, immune cells are educated (by microbiota and food) to provide tolerance to those foreign agents, and finally, the epithelium matures to also deal with all these changes. We study how these actors orchestrate early-life gut development.
- Immunity to infection: Our gut is a common site for some devastating infections by pathogens such as bacteria, viruses, fungi, and helminths. Each pathogen requires a different host response to generate immunity. We study how intestinal epithelium is involved in regulating immune responses, from mounting them to the ultimate effector response needed for pathogen clearance.
- Epithelial repair after damage: Many agents can cause damage in the gut. For example, radiation during cancer treatment, inflammation in inflammatory bowel diseases (IBD), infection by pathogens. After damage, the epithelium needs to quickly cover the wound and rebuild its structure to regain its barrier and nutrient uptake function. We study how reparative processes are regulated intrinsically by the epithelium.
Please see below some selected publications that cover the topics described above.
Lindholm HT, Parmar N, Drurey C, Campillo Poveda M, Vornewald PM, Ostrop J, Díez-Sanchez A, Maizels RM, Oudhoff MJ. BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13-driven tuft cell hyperplasia. Science Immunology 2022 May 13;7(71):eabl6543
Drurey C, Lindholm HT, Coakley G, Loeser S, Doolan R, Gerbe F, Jay P, Harris N, Oudhoff MJ, Maizels RM. Intestinal tuft cell induction by type 2 cytokines is negated by a helminth parasite and its secreted products. Journal of Experimental Medicine 2022 Jan 3;219(1):e20211140
Martin-Alonso M, Iqbal S, Vornewald PM, Lindholm HT, Damen MJ, Martínez F, Hoel S, Díez-Sánchez A, Altelaar M, Katajisto P, Arroyo AG, Oudhoff MJ. Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage. Nature Communications 2021 Nov 18; 12(1):6741
Chetty A, Darby M, Vornewald PM, Martín-Alonso M, Filz A, Ritter M, McSorley H, Masson L, Smith K, Brombacher F, O’Shea M, Cunningham A, Ryffel B, Oudhoff MJ, Dewals B, Layland L, Horsnell W. Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology following HSV-2 infection. Cell Host & Microbe 2021 Apr 14;29(4):579-593.e.5.
Parmar N, Burrows K, Vornewald PM, Lindholm HT, Zwiggelaar RT, Díez-Sánchez A, Martin-Alonso M, Fosslie M, Vallance B, Arne Dahl J, Zaph C, Oudhoff MJ. Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection. PLoS Pathogens 2021 Mar 31;13(3):e1009476 2020
Roberts LB, Schnoeller C, Berkachy R, Darby M, Pillaye J, Oudhoff MJ, Parmar N, Mackowiak C, Sedda D, Quesniaux V, Ryffel B, Vaux R, Gounaris K, Berrard S, Withers DR, Horsnell WG, Selkirik ME. Acetylcholine production by type 2 innate lymphoid cells promotes mucosal immunity to helminth parasites. Science Immunology 2021 Mar 5;6(57):eabd0359
Ostrop J, Zwiggelaar R, Terndrup Pedersen M, Gerbe F, Bosl K, Lindholm H, Diez-Sanchez A, Parmar N, Radetzki S, von Kries J, Jay P, Jensen K, Arrowsmith C, Oudhoff MJ. A semi-automated screening method demonstrates epigenetic control of intestinal epithelial differentiation. Frontiers in Cell and Developmental Biology 2021 Jan 21;8:618552.
Zwiggelaar RT, Lindholm HT, Fosslie M, Terndrup Pedersen M, Ohta Y, Díez-Sanchez A, Martín-Alonso M, Ostrop J, Matano M, Parmar N, Kvaløy E, Spanjers RR, Nazmi K, Rye M, Drabløs F, Arrowsmith C, Arne Dahl J, Jensen KB, Sato T, and Oudhoff MJ. LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium. Science Advances 2020 11;6(37):eabc0367
Oudhoff MJ*, Antignano F*, Chenery AL, Braam MJ, Zaph C. Intestinal epithelial cell-intrinsic deletion of Setd7 identifies crucial roles for developmental pathways in immunity against parasitic and bacterial infections. PLoS Pathogens 2016 Sep 6; 12(9): e1005876. *equal contribution
Oudhoff MJ, Braam MJS, Freeman SA, Wong D, Rattray DG, Wang J, Antignano F, Snyder K, Refaeli I, Hughes MR, McNagny KM, Gold MR, Arrowsmith CH, Sato T, Rossi FMV, Tatlock JH, Owen DR, Brown PJ, Zaph C. SETD7 controls intestinal regeneration and tumorigenesis by regulating Wnt/b-Catenin and Hippo/YAP signaling. Developmental Cell 2016 37 (1): 47–57.