Science Portrait: Dr. Menno J. Oudhoff

This is a summary of the curriculum vitae (CV) of Dr. Menno Oudhoff, Associate Professor, Department of Health Sciences, Faculty of Science, Carleton University, Ottawa, Canada. On September 30, he will give a presentation at Fujita Health University.

Dr. Oudhoff is from the Netherlands, where he got his master’s degree in Biology in 2006 (he is still young), and from then has had a number of exciting research positions studying mucosal tissues in the Netherlands, Canada, Norway, South Africa, and now again Canada. He is definitely “up and coming,” with, even within 2021-2022 alone, publications as last author in journals like Science Immunology, Cell Host & Microbe, Nature Communications, and PLoS Pathogens.

He was brought to my attention as an excellent speaker by Prof. Jim Kaufman, whom many of you know as a previous speaker and a regular visitor of our seminars. Knowing how critical Prof. Kaufman is, I am sure about Dr. Oudhoff’s ability to give an engaging presentation.

After completing his MSc degree in Biology in 2006, Dr. Oudhoff did his PhD at the Department of Oral Biochemistry (VU University, Amsterdam) under supervision of Dr. Enno Veerman. There, he showed that histatins, salivary peptides, not only have antimicrobial activity but also promote wound healing by affecting epithelial cell behavior (Oudhoff et al. 2008). The interplay at our mucosal barriers between the immune system, cell growth, and tissue homeostasis/formation has intrigued him ever since. Naturally, because of his interest in these overlap functions, the arm of the immune system that he would often encounter in his research is “Type 2” immunity, which fights helminths (parasitic worms) but also promotes wound repair and, unfortunately, tumor growth.

From 2011 to 2016, as a postdoctoral researcher, he joined the Mucosal Immunology lab of Dr. Colby Zaph at the University of British Columbia in Vancouver, Canada, to study another mucosal organ, the intestine. Like the oral cavity, also the intestine is characterized by rapidly growing epithelial cells (with a turnover rate of about five days) and the necessity to maintain homeostasis (be stable and tolerant) in the presence of foreign food particles and commensal microorganisms. In Vancouver, Dr. Oudhoff’s initial focus was on intestinal helminth infection, but he soon also became interested in the cellular pathways that promote cell regeneration (replacing of dying cells by new cells derived from stem cells) and cancer. In this period, he found that Set7, a lysine methyltransferase, promotes the Hippo and Wnt pathways of cell proliferation, and is important for regeneration and cancer formation of intestinal epithelial cells (IEC) (Oudhoff et al. 2013; 2016a). Furthermore, he found that Set7 was important for the Type 2 immune defense mechanism of expelling helminth worms by increased turnover rates of IECs (Oudhoff et al. 2016b).

Dr. Oudhoff’s achievements in Vancouver landed him, in 2016, a position as group leader at the Centre for Molecular Inflammation Research (CEMIR) at the Norwegian University of Science and Technology (NTNU), Trondheim, Norway, where he worked until very recently. In Norway, his major research topic remained the intestinal barrier function, focusing on interactions between immune factors and IEC cell phenotypes (e.g., Parmar et al. 2021; Drurey et al. 2022; Lindholm et al. 2022). During his Norway period, he also spent seven months in the lab of Dr. William Horsnell, University of Cape Town, South Africa, participating in work on helminths.

Just a few months ago, this year, he returned to Canada to become an associate professor at Carleton University in Ottawa. His main interests there remain intestinal mucosal immunology and IEC biology, with also an accent now on how the intestine develops and changes during our first year of life.

Mucosal barriers, where immune functions interplay with rapidly dividing epithelial cells and—depending on the organ—large numbers of commensal microorganisms, are a critical part of our bodies. It should be great to have someone like Dr. Oudhoff explain about this.

CURRICULUM VITAE

EDUCATION:

2006  MSc degree, Biology, Faculty of Earth and Life Sciences, VU University, Amsterdam, NL.

2010  PhD degree (December 7th, 2010). Enno C.I. Veerman (supervisor) Faculty of Dentistry, Department of Oral Biochemistry, VU University, Amsterdam, The Netherlands (NL)

Thesis Title: Discovery of the wound-healing capacity of salivary histatins.

PROFESSIONAL EXPERIENCE:

2011-2016  Postdoctoral researcher, The Biomedical Research Centre, University of British Columbia (UBC), Vancouver, Canada. Colby Zaph (supervisor)

2016 – 2022  Group Leader, Centre for Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

2020  Visiting Researcher, Laboratory of Parasite Immune Regulation (Dr. William Horsnell), University of Cape Town, South Africa (7 months)

2022 – now Associate Professor, Department of Health Sciences, Faculty of Science, Carleton University

CAREER DEVELOPMENT:

2017-2021  Outstanding Fellow program (NTNU), 3 two-day retreats each year covering various aspects in professional development 2020 ERC workshop Sex and Gender dimension in Frontier research (1 day)

2017  EMBO Laboratory Leadership Course (4 days), Heidelberg, Germany 2016 PhD supervisor workshop (2 days), NTNU, Norway

AWARDS

2006  Scholarship award, 1 week, PhD course ‘regeneration of epidermal-mesenchymal organs’ COST Action B23, Paris, France

2008  IOT-Glaxo Smith Klein Best Presentation Award, Research days for Dutch Dentistry, The Netherlands

2011  Best research publication award, Dutch Society for Oral Biology, The Netherlands

2013  Young Investigator Travel Award, 16th International Congress of Mucosal Immunology, Vancouver, BC, Canada

2014  Travel Award Till and McCulloch Meeting, Ottawa, ON, Canada

2015  Travel Award Till and McCulloch Meeting, Toronto, ON, Canada

REVIEWER FUNCTIONS:

Dr. Oudhoff has acted as a reviewer for the following journals: Nature Chemical Biology, Mucosal Immunology, Parasites, eLife, Stem Cell Reports, Cellular and Molecular Immunology, FASEB Journal, Journal of Ophthalmology, Journal of Immunology Research, and Placenta.

PUBLICATIONS

Perspectives / Commentaries (not peer-reviewed)

1. Vornewald PM, Oudhoff MJ. Helminths get MIFfed by the tuft cell – ILC2 circuit. 2022 Immunology and Cell Biology May; 100(5):301-303.

2. Horsnell WGC, Oudhoff MJ. Helminths are positively AMPing up gut de-bugging. 2022 Cell Host & Microbe 2022 Jan 12;30(1):1-2.

Peer reviewed publications:

1. 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. 2022 Science Immunology May 13;7(71):eabl6543.

2. 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. 2022 Journal of Experimental Medicine Jan 3;219(1):e20211140.

3. Martin-Alonso M, Iqbal S, Vornewald PM, Lindholm HT, Damen MJ, Martínez F, Hoel S, DíezSánchez 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. 2021 Nature Communications Nov 18; 12(1):6741.

4. 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. 2021 Cell Host & Microbe Apr 14;29(4):579-593.e.5.

5. Parmar N, Burrows K, Vornewald PM, Lindholm HT, Zwiggelaar RT, Díez-Sánchez A, MartinAlonso 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. 2021 PLoS Pathogens Mar 31;13(3):e1009476 2020.

6. 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. (image was selected for the cover)

7. 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 semiautomated screening method demonstrates epigenetic control of intestinal epithelial differentiation. Frontiers in Cell and Developmental Biology 2021 Jan 21;8:618552.

8. 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. *co-first

9. Judson RN, Quarta M*, Oudhoff MJ*, Soliman H, Chang CK, Yi L, Lou G, Hamer M, Blonigan J, He WJ, Su L, Zhang RH, Xu P, Cait A, Vander Werff R, Eisner C, Lewis CA, Low M, Barta I, Karimi MM, Zaph C, Rando TA, and Rossi FM. Inhibition of methyltransferase Setd7 allows the Curriculum Vitae Menno J Oudhoff 7 of 8 in vitro expansion of myogenic stem cells with improved therapeutic potential. Cell Stem Cell. 2018 22 (2) 177-190. *equal contribution

10. Gómez-Escudero J, Moreno V, Martín-Alonso M, Hernández-Riquer V, Feinberg T, Colmenar Á, Calvo E, Camafeita E, Martínez F, Oudhoff MJ, Weiss SJ, Arroyo AG. E-Cadherin cleavage by MT2-MMP regulates apical junctional signaling and epithelial homeostasis in the intestine. J. Cell Science. 2017 130 (23), 4013-4027. (image was selected for the cover)

11. Oudhoff MJ*† , Antignano F*, Chenery AL, Braam MJ, Zaph C† . Intestinal epithelial cellintrinsic 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 † co-corresponding

12. Antignano F, Braam MJS, Hughes MR, Chenery A, Burrows K, Gold MJ, Oudhoff MJ, Rattray D, Halim T, Cait AM, Takei F, Rossi FMV, McNagny KM, Zaph C. G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program. J. Exp. Med. 2016 213 (7): 1153-62.

13. 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. † cocorresponding

14. Barsyte-Lovejoy D*, Li F*, Oudhoff MJ*, Tatlock JH*, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA, Kuznetsova E, Marcellus R, Allali-Hassani A, Kennedy S, Lambert JP, Couzens AL, Aman A, Gingras A-C, Al-Awar R, Fish PV, Gerstenberger BS, Roberts L, Benn CL, Grimley RL, Braam MJS, Rossi FMV, Sudol M, Brown PJ, Bunnage ME, Owen DR, Zaph C, Vedadi M, Arrowsmith CH. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. PNAS 2014 111 (35): 12853–12858. *equal contribution

15. Antignano F, Burrows K, Hughes, ML, Han JM, Kron KJ, Penrod NM, Oudhoff MJ, Wang SKH, Min PH, Gold MJ, Chenery A, Braam MJS, Fung TC, Rossi FMV, McNagny KM, Arrowsmith CH, Lupien M, Levings MK, Zaph C. Methyltransferase G9A regulates T cell differentiation during murine intestinal inflammation. J. Clin. Invest. 2014 124 (5):1945–1955.

16. Mullaly SC, Oudhoff MJ, Min PH, Burrows, K, Antignano F, Rattray DG, Chenery A, McNagny KM, Ziltener HJ, Zaph C. Requirement for Core 2 O-Glycans for Optimal Resistance to Helminth Infection. PLoS ONE 2013 8 (3): e60124.

17. Oudhoff MJ, Freeman SA, Couzens AL, Antignano F, Min PH, Northrop JP, Burrows K, Chenery A, Lehnertz B, Barsyte-Lovejoy D, Vedadi M, Arrowsmith CH, Nishina H, Gold MR, Rossi FMV, Gingras A-C, Zaph C. Regulation of the Hippo pathway through Set7-dependent methylation of Yap. Developmental Cell 2013 26 (2): 188–194.

18. Bron JL, Mulder HW, Vonk LA, Doulabi DZ, Oudhoff MJ, Smit TH. Migration of intervertebral disc cells into dense collagen scaffolds intended for functional replacement. J. Mat. Sci.: Mat. in Med. 2012 23(3): 813-21.

19. Bolscher JG*, Oudhoff MJ*, Nazmi K, Antos JM, Guimareas CP, Spooner E, Haney EF, Garcia Vallejo JJ, Vogel HJ, van ‘t Hof W, Ploegh HL, Veerman EC. Sortase A as a tool for high-yield histatin cyclization. FASEB J. 2011 25(8): 2650-8. *equal contribution

20. Oudhoff MJ, Blaauboer ME, Nazmi K, Scheres N, Bolscher JG, Veerman EC. The role of salivary histatin and the human Cathelicidin LL-37 in wound healing and innate immunity. Biol. Chem. 2010 391(5): 541-48.

21. Oudhoff MJ, Kroeze KL, Nazmi K, van den Keijbus PA, van ‘t Hof W, Fernandez-Borja M, Hordijk PL, Gibbs S, Bolscher JG, Veerman EC. Structure-activity analysis of histatin, a potent wound healing peptide from human saliva: cyclization of histatin potentiates molar activity 1,000- fold. FASEB J. 2009 23(11):3928-35.

22. Oudhoff MJ, van den Keijbus PA, Kroeze KL, Nazmi K, Gibbs S, Bolscher JG, Veerman EC. Histatins enhance wound closure with oral and non-oral cells. J. Dent. Res. 2009 88(9):846-50.

23. Oudhoff MJ, Bolscher JG, Nazmi K, Kalay H, van ‘t Hof W, Amerongen AV, Veerman EC. Histatins are the major wound-closure stimulating factors in human saliva as identified in a cell culture assay. FASEB J. 2008 22(11):3805-12.

24. de Jong MA*, de Witte L*, Oudhoff MJ, Gringhuis SI, Gallay P, Geijtenbeek TB. TNF-alpha and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo. J. Clin. Invest. 2008 118(10):3440-52. *equal contribution

Book chapter

1. van ‘t Hof W, Oudhoff MJ, Veerman ECI (2013) Chapter 9: Histatins: multifunctional salivary antimicrobial peptides (Springer Basel AG). Antimicrobial peptides and innate immunity (Edited by Drs. P.S. Hiemstra and S.A. Zaat)