Jeremy A. Goettel, PhD

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Office Address:
2215B Garland Ave., MRB IV, Room / Suite 1075J, Nashville, TN 37232-0252

Assistant Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition

Research Description

Our lab is interested in understanding the mechanisms regulating intestinal immunity and what leads to dysregulation and disease as well as how gut microbes shape the mucosal immune system. In particular the cytokine interleukin-23 (IL23) is required for the development of many experimental models of inflammatory bowel disease (IBD) in mice and mutations in IL23 receptor (IL23R) have been identified as susceptibility or resistance factors for Crohn’s disease. We have developed several murine strains that will facilitate investigations into the role of IL23R signaling in a cell-specific manner using experimental models of IBD and inflammation-associated carcinogenesis. In addition, we have developed several humanized murine systems to model intestinal inflammation driven by human immune cells and new models enabling engraftment of human tumors with autologous immune cells to assess combination therapies and immune activation. We hope that these strategies will be informative for clinical management and pave the way towards precision medicine.

Brief Description

Dr. Jeremy Goettel recently joined the Vanderbilt faculty in the Department of Medicine, Division of Gastroneterology, Hepatology, and Nutrition. He received his PhD in cell and developmental biology from Vanderbilt University in 2010 where he studied cytokine signaling in intestinal epithelial cells in the lab of Dr. Brent Polk. He performed his postdoctoral training with Dr. Scott Snapper at Harvard Medical School and Boston Children’s Hospital where he investigated mechanisms of mucosal immune regulation with a particular focus on monogenic disorders driving inflammatory bowel diseases. During this time, Dr. Goettel developed and utilized humanized murine systems as translational research tools that enabled studies related to human immune-mediated diseases, human immunobiology, and assessing human therapeutics. His contributions to the field of humanized mice, mucosal immunology, and inflammatory bowel disease earned him a Young Investigator Award from the International Workshop on Humanized Mice and, more recently, the prestigious CCFA Shanti Sitaraman Young IBD Investigator Award. Dr. Goettel’s research at Vanderbilt will focus on defining the roles specific regulatory T cells and innate lymphoid cells play in mucosal immune homeostasis and inflammation-associated carcinogenesis using both genetic and humanized murine systems.

Email
jeremy.goettel@vumc.org

Education

PhD - Vanderbilt University

Publications

Redhu NS, Bakthavatchalu V, Conaway EA, Shouval DS, Tsou A, Goettel JA, Biswas A, Wang C, Field M, Muller W, Bleich A, Li N, Gerber GK, Bry L, Fox JG, Snapper SB, Horwitz BH. Macrophage dysfunction initiates colitis during weaning of infant mice lacking the interleukin-10 receptorElife. 2017 Jul 7/5/2017; 6: PMID: 28678006, PMCID: PMC5531923, DOI: 10.7554/eLife.27652, ISSN: 2050-084X.

Lexmond WS, Goettel JA, Sallis BF, McCann K, Rings EHHM, Jensen-Jarolim E, Nurko S, Snapper SB, Fiebiger E. Spontaneous food allergy in Was(-/-) mice occurs independent of FceRI-mediated mast cell activationAllergy [print-electronic]. 2017 Jun 6/10/2017; PMID: 28600891, DOI: 10.1111/all.13219, ISSN: 1398-9995.

Sugimura R, Jha DK, Han A, Soria-Valles C, da Rocha EL, Lu YF, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Zhu TN, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, Daley GQ. Haematopoietic stem and progenitor cells from human pluripotent stem cellsNature [print-electronic]. 2017 May 5/25/2017; 545(7655): 432-8. PMID: 28514439, PII: nature22370, DOI: 10.1038/nature22370, ISSN: 1476-4687.

Schoellhammer CM, Lauwers GY, Goettel JA, Oberli MA, Cleveland C, Park JY, Minahan D, Chen Y, Anderson DG, Jaklenec A, Snapper SB, Langer R, Traverso G. Ultrasound-Mediated Delivery of RNA to Colonic Mucosa of Live MiceGastroenterology [print-electronic]. 2017 Apr; 152(5): 1151-60. PMID: 28088460, PMCID: PMC5368009, PII: S0016-5085(17)30013-6, DOI: 10.1053/j.gastro.2017.01.002, ISSN: 1528-0012.

Thiagarajah JR, Chang J, Goettel JA, Verkman AS, Lencer WI. Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epitheliaProc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Jan 1/17/2017; 114(3): 568-73. PMID: 28049834, PMCID: PMC5255594, PII: 1612921114, DOI: 10.1073/pnas.1612921114, ISSN: 1091-6490.

Goettel JA, Gandhi R, Kenison JE, Yeste A, Murugaiyan G, Sambanthamoorthy S, Griffith AE, Patel B, Shouval DS, Weiner HL, Snapper SB, Quintana FJ. AHR Activation Is Protective against Colitis Driven by T Cells in Humanized MiceCell Rep. 2016 Oct 10/25/2016; 17(5): 1318-29. PMID: 27783946, PMCID: PMC5106873, PII: S2211-1247(16)31355-9, DOI: 10.1016/j.celrep.2016.09.082, ISSN: 2211-1247.

Lexmond WS, Goettel JA, Lyons JJ, Jacobse J, Deken MM, Lawrence MG, DiMaggio TH, Kotlarz D, Garabedian E, Sackstein P, Nelson CC, Jones N, Stone KD, Candotti F, Rings EH, Thrasher AJ, Milner JD, Snapper SB, Fiebiger E. FOXP3+ Tregs require WASP to restrain Th2-mediated food allergyJ. Clin. Invest [print-electronic]. 2016 Oct 10/3/2016; 126(10): 4030-44. PMID: 27643438, PMCID: PMC5096801, PII: 85129, DOI: 10.1172/JCI85129, ISSN: 1558-8238.

Nelms BD, Waldron L, Barrera LA, Weflen AW, Goettel JA, Guo G, Montgomery RK, Neutra MR, Breault DT, Snapper SB, Orkin SH, Bulyk ML, Huttenhower C, Lencer WI. CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell typesGenome Biol. 2016 Sep 9/29/2016; 17(1): 201. PMID: 27687735, PMCID: PMC5043525, PII: 10.1186/s13059-016-1062-5, DOI: 10.1186/s13059-016-1062-5, ISSN: 1474-760X.

Goettel JA, Biswas S, Lexmond WS, Yeste A, Passerini L, Patel B, Yang S, Sun J, Ouahed J, Shouval DS, McCann KJ, Horwitz BH, Mathis D, Milford EL, Notarangelo LD, Roncarolo MG, Fiebiger E, Marasco WA, Bacchetta R, Quintana FJ, Pai SY, Klein C, Muise AM, Snapper SB. Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3Blood [print-electronic]. 2015 Jun 6/18/2015; 125(25): 3886-95. PMID: 25833964, PMCID: PMC4473116, PII: blood-2014-12-618363, DOI: 10.1182/blood-2014-12-618363, ISSN: 1528-0020.

Vucovich MM, Cotton RB, Shelton EL, Goettel JA, Ehinger NJ, Poole SD, Brown N, Wynn JL, Paria BC, Slaughter JC, Clark RH, Rojas MA, Reese J. Aminoglycoside-mediated relaxation of the ductus arteriosus in sepsis-associated PDAAm. J. Physiol. Heart Circ. Physiol [print-electronic]. 2014 Sep 9/1/2014; 307(5): H732-40. PMID: 24993047, PMCID: PMC4187398, PII: ajpheart.00838.2013, DOI: 10.1152/ajpheart.00838.2013, ISSN: 1522-1539.

Shouval DS, Biswas A, Goettel JA, McCann K, Conaway E, Redhu NS, Mascanfroni ID, Al Adham Z, Lavoie S, Ibourk M, Nguyen DD, Samsom JN, Escher JC, Somech R, Weiss B, Beier R, Conklin LS, Ebens CL, Santos FG, Ferreira AR, Sherlock M, Bhan AK, Müller W, Mora JR, Quintana FJ, Klein C, Muise AM, Horwitz BH, Snapper SB. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage functionImmunity [print-electronic]. 2014 May 5/15/2014; 40(5): 706-19. PMID: 24792912, PMCID: PMC4513358, PII: S1074-7613(14)00125-3, DOI: 10.1016/j.immuni.2014.03.011, ISSN: 1097-4180.

Shouval DS, Ouahed J, Biswas A, Goettel JA, Horwitz BH, Klein C, Muise AM, Snapper SB. Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humansAdv. Immunol. 2014; 122: 177-210. PMID: 24507158, PMCID: PMC4741283, PII: B978-0-12-800267-4.00005-5, DOI: 10.1016/B978-0-12-800267-4.00005-5, ISSN: 1557-8445.

Nguyen DD, Muthupalani S, Goettel JA, Eston MA, Mobley M, Taylor NS, McCabe A, Marin R, Snapper SB, Fox JG. Colitis and colon cancer in WASP-deficient mice require helicobacter speciesInflamm. Bowel Dis. 2013 Sep; 19(10): 2041-50. PMID: 23820270, PMCID: PMC4082694, DOI: 10.1097/MIB.0b013e318295fd8f, ISSN: 1536-4844.

Lexmond WS, Pardo M, Rooney K, Goettel JA, Snapper SB, Yen EH, Dehlink E, Nurko S, Fiebiger E. Elevated levels of leukotriene C4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patientsClin. Exp. Allergy. 2013 Aug; 43(8): 902-13. PMID: 23889244, PMCID: PMC3728707, DOI: 10.1111/cea.12146, ISSN: 1365-2222.

Weitkamp JH, Koyama T, Rock MT, Correa H, Goettel JA, Matta P, Oswald-Richter K, Rosen MJ, Engelhardt BG, Moore DJ, Polk DB. Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratiosGut [print-electronic]. 2013 Jan; 62(1): 73-82. PMID: 22267598, PMCID: PMC3606820, PII: gutjnl-2011-301551, DOI: 10.1136/gutjnl-2011-301551, ISSN: 1468-3288.

Nguyen DD, Wurbel MA, Goettel JA, Eston MA, Ahmed OS, Marin R, Boden EK, Villablanca EJ, Paidassi H, Ahuja V, Reinecker HC, Fiebiger E, Lacy-Hulbert A, Horwitz BH, Mora JR, Snapper SB. Wiskott-Aldrich syndrome protein deficiency in innate immune cells leads to mucosal immune dysregulation and colitis in miceGastroenterology [print-electronic]. 2012 Sep; 143(3): 719-729.e2. PMID: 22710191, PMCID: PMC3760724, PII: S0016-5085(12)00824-4, DOI: 10.1053/j.gastro.2012.06.008, ISSN: 1528-0012.

Hobbs SS, Goettel JA, Liang D, Yan F, Edelblum KL, Frey MR, Mullane MT, Polk DB. TNF transactivation of EGFR stimulates cytoprotective COX-2 expression in gastrointestinal epithelial cellsAm. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2011 Aug; 301(2): G220-9. PMID: 21566012, PMCID: PMC3154604, PII: ajpgi.00383.2010, DOI: 10.1152/ajpgi.00383.2010, ISSN: 1522-1547.

Zhang Y, Li X, Carpinteiro A, Goettel JA, Soddemann M, Gulbins E. Kinase suppressor of Ras-1 protects against pulmonary Pseudomonas aeruginosa infectionsNat. Med [print-electronic]. 2011 Mar; 17(3): 341-6. PMID: 21297617, PII: nm.2296, DOI: 10.1038/nm.2296, ISSN: 1546-170X.

Goettel JA, Liang D, Hilliard VC, Edelblum KL, Broadus MR, Gould KL, Hanks SK, Polk DB. KSR1 is a functional protein kinase capable of serine autophosphorylation and direct phosphorylation of MEK1Exp. Cell Res [print-electronic]. 2011 Feb 2/15/2011; 317(4): 452-63. PMID: 21144847, PMCID: PMC3038243, PII: S0014-4827(10)00547-1, DOI: 10.1016/j.yexcr.2010.11.018, ISSN: 1090-2422.

Goettel JA, Scott Algood HM, Olivares-Villagómez D, Washington MK, Chaturvedi R, Wilson KT, Van Kaer L, Polk DB. KSR1 protects from interleukin-10 deficiency-induced colitis in mice by suppressing T-lymphocyte interferon-¿ productionGastroenterology [print-electronic]. 2011 Jan; 140(1): 265-74. PMID: 20875416, PMCID: PMC3008308, PII: S0016-5085(10)01421-6, DOI: 10.1053/j.gastro.2010.09.041, ISSN: 1528-0012.

Edelblum KL, Goettel JA, Koyama T, McElroy SJ, Yan F, Polk DB. TNFR1 promotes tumor necrosis factor-mediated mouse colon epithelial cell survival through RAF activation of NF-kappaBJ. Biol. Chem [print-electronic]. 2008 Oct 10/24/2008; 283(43): 29485-94. PMID: 18713739, PMCID: PMC2570867, PII: M801269200, DOI: 10.1074/jbc.M801269200, ISSN: 0021-9258.

McElroy SJ, Frey MR, Yan F, Edelblum KL, Goettel JA, John S, Polk DB. Tumor necrosis factor inhibits ligand-stimulated EGF receptor activation through a TNF receptor 1-dependent mechanismAm. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2008 Aug; 295(2): G285-93. PMID: 18467504, PMCID: PMC2519857, PII: 00425.2007, DOI: 10.1152/ajpgi.00425.2007, ISSN: 0193-1857.