Image Place holder

Caroline Appleyard, PhD



    • Cancer Biology and Evolution Program

Education & Training


  • University of Southampton, UK - PhD - Clinical Pharmacology Group


  • University of Calgary, Fellow - GI Phys/Pharm
  • University of South Dakota, Fellow - GI Phys/Pharm

Dr. Appleyard's research interests are in the molecular basis of ulcerative colitis-associated dysplasia. One of the complications of Ulcerative Colitis is an increased risk for the development of cancer of the colon and rectum. Little is know about the transition from chronic inflammation into dysplasia and colorectal cancer, so the lab is currently attempting to develop a model of colitis-associated dysplasia which could be used to identify genetic alterations present in tumors. We will compare the development of dysplasia in animals which have tumors induced by a well-known carcinogen to that observed in animals with long term chronic intestinal inflammation, and controls. Dr. Appleyard and her associates aim to establish a profile of cancer related gene mutations (specifically p53, K-ras and APC) during the transition of inflammation to dysplasia, and correlate these with both histological and inflammatory changes. This may thus provide a molecular tool for improved estimation of diagnosis in patients with long standing ulcerative colitis as to their progression to colorectal cancer.


  • Pagán-Busigó JE, López-Carrasquillo J, Appleyard CB, Torres-Reverón A. Beyond depression and anxiety; a systematic review about the role of corticotropin-releasing hormone antagonists in diseases of the pelvic and abdominal organs. PLoS One. 2022 Mar.17(3):e0264909. Pubmedid: 35275963. Pmcid: PMC8916623.
  • Ortiz CN, Torres-Reverón A, Appleyard CB. Metabolomics in endometriosis: challenges and perspectives for future studies. Reprod Fertil. 2021 Apr.2(2):R35-R50. Pubmedid: 35128453. Pmcid: PMC8812441.
  • Appleyard CB, Flores I, Torres-Reverón A. The Link Between Stress and Endometriosis: from Animal Models to the Clinical Scenario. Reprod Sci. 2020 Sep.27(9):1675-1686. Pubmedid: 32542543.
  • Seguinot-Tarafa I, Luna N, Suarez E, Appleyard CB, Flores I. Inhibition of Histone Methyltransferase EZH2 Suppresses Endometriotic Vesicle Development in a Rat Model of Endometriosis. Reprod Sci. 2020 Sep.27(9):1812-1820. Pubmedid: 32651901. Pmcid: PMC9092274.
  • Torres-Reverón A, Rana M, Gorabi V, Rivera-Lopez LL, Appleyard CB. Short treatment with antalarmin alters adrenal gland receptors in the rat model of endometriosis. PLoS One. 2020 Jan.15(1):e0227456. Pubmedid: 31935235. Pmcid: PMC6959558.
  • Lopez A, Cruz ML, Chompre G, Hernández S, Isidro RA, Flores I, Appleyard CB. Influence of Stress on the Vitamin D-Vitamin D Receptor System, Macrophages, and the Local Inflammatory Milieu in Endometriosis. Reprod Sci. 2020 Dec.27(12):2175-2186. Pubmedid: 32583376.
  • Rivera J, Isidro RA, Loucil-Alicea RY, Cruz ML, Appleyard CB, Isidro AA, Chompre G, Colon-Rivera K, Noel RJ. Infusion of HIV-1 Nef-expressing astrocytes into the rat hippocampus induces enteropathy and interstitial pneumonitis and increases blood-brain-barrier permeability. PLoS One. 2019 Nov.14(11):e0225760. Pubmedid: 31774879. Pmcid: PMC6881014.
  • Torres-Reverón A, Rivera LL, Flores I, Appleyard CB. Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression. Reprod Sci. 2018 Sep.25(9):1336-1348. Pubmedid: 29137551. Pmcid: PMC6346300.
  • Martinez-Orengo N, Cruz ML, Velazquez B, Noel RJ, Appleyard CB. Nurturing interest in science and understanding the role of a scientist by teaching younger students how to apply scientific thinking during daily activities. Adv Physiol Educ. 2018 Sep.42(3):466-472. Pubmedid: 29972061. Pmcid: PMC6334932.
  • Torres-Reverón A, Rivera-Lopez LL, Flores I, Appleyard CB. Antagonizing the corticotropin releasing hormone receptor 1 with antalarmin reduces the progression of endometriosis. PLoS One. 2018 Nov.13(11):e0197698. Pubmedid: 30427841. Pmcid: PMC6235236.
  • Cuevas M, Cruz ML, Ramirez AE, Flores I, Thompson KJ, Bayona M, Vernon MW, Appleyard CB. Stress During Development of Experimental Endometriosis Influences Nerve Growth and Disease Progression. Reprod Sci. 2018 Mar.25(3):347-357. Pubmedid: 29108503. Pmcid: PMC6343219.
  • Hernandez S, Cruz ML, Seguinot II, Torres-Reveron A, Appleyard CB. Impact of Psychological Stress on Pain Perception in an Animal Model of Endometriosis. Reprod Sci. 2017 Oct.24(10):1371-1381. Pubmedid: 28093054. Pmcid: PMC5933089.
  • Hernandez S, Cruz ML, Torres-Reveron A, Appleyard CB. Impact of physical activity on pain perception in an animal model of endometriosis. J Endometr Pelvic Pain Disord. 2017 Feb.7(3):89-114. Pubmedid: 28217664. Pmcid: PMC5310711.
  • Isidro RA, Lopez A, Cruz ML, Gonzalez Torres MI, Chompre G, Isidro AA, Appleyard CB. The Probiotic VSL#3 Modulates Colonic Macrophages, Inflammation, and Microflora in Acute Trinitrobenzene Sulfonic Acid Colitis. J Histochem Cytochem. 2017 08.65(8):445-461. Pubmedid: 28692320. Pmcid: PMC5533272.
  • Torres-Reverón A, Palermo K, Hernández-López A, Hernández S, Cruz ML, Thompson KJ, Flores I, Appleyard CB. Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray. Reprod Sci. 2016 Sep.23(9):1158-1167. Pubmedid: 27089914. Pmcid: PMC5933161.
  • Isidro RA, Appleyard CB. Colonic macrophage polarization in homeostasis, inflammation, and cancer. Am J Physiol Gastrointest Liver Physiol. 2016 Jul.311(1):G59-G73. Pubmedid: 27229123. Pmcid: PMC4967174.
  • Abreu-Delgado Y, Isidro RA, Torres EA, González A, Cruz ML, Isidro AA, González-Keelan CI, Medero P, Appleyard CB. Serum vitamin D and colonic vitamin D receptor in inflammatory bowel disease. World J Gastroenterol. 2016 Apr.22(13):3581-3591. Pubmedid: 27053850. Pmcid: PMC4814644.
  • de Jesus ER, Isidro RA, Cruz ML, Marty H, Appleyard CB. Adoptive Transfer of Dendritic Cells Expressing Fas Ligand Modulates Intestinal Inflammation in a Model of Inflammatory Bowel Disease. J Clin Cell Immunol. 2016 Apr.7(2). Pubmedid: 27274906. Pmcid: PMC4892183.
  • Isidro RA, Cruz ML, Isidro AA, Baez A, Arroyo A, González-Marqués WA, González-Keelan C, Torres EA, Appleyard CB. Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia. World J Gastroenterol. 2015 Feb.21(6):1749-1758. Pubmedid: 25684939. Pmcid: PMC4323450.
  • Isidro RA, Isidro AA, Cruz ML, Hernandez S, Appleyard CB. Double immunofluorescent staining of rat macrophages in formalin-fixed paraffin-embedded tissue using two monoclonal mouse antibodies. Histochem Cell Biol. 2015 Dec.144(6):613-621. Pubmedid: 26403093. Pmcid: PMC4758119.
  • Appleyard CB, Cruz ML, Hernández S, Thompson KJ, Bayona M, Flores I. Stress management affects outcomes in the pathophysiology of an endometriosis model. Reprod Sci. 2015 Apr.22(4):431-441. Pubmedid: 25015902. Pmcid: PMC4812689.
  • Pacheco WI, Noel RJ, Porter JT, Appleyard CB. Beyond the GRE: using a composite score to predict 
the success of Puerto Rican students in a biomedical 
PhD program. CBE Life Sci Educ. 2015.14(2). Pubmedid: 25828404. Pmcid: PMC4477729.
  • Appleyard CB, Antonia SJ, Sullivan DM, Santiago-Cardona PG, Cáceres W, Velez H, Torres-Ruiz JA, Wright KL. Building a long distance training program to enhance clinical cancer research capacity in Puerto Rico. Rev Recent Clin Trials. 2014 Dec.9(4):254-262. Pubmedid: 25626061. Pmcid: PMC4378863.
  • Baez A, Pacheco W, Appleyard CB. The graduate student portfolio: organize and energize your career development. Physiologist. 2012 Oct.55(5):177-178. Pubmedid: 23155926.
  • Cuevas M, Flores I, Thompson KJ, Ramos-Ortolaza DL, Torres-Reveron A, Appleyard CB. Stress exacerbates endometriosis manifestations and inflammatory parameters in an animal model. Reprod Sci. 2012 Aug.19(8):851-862. Pubmedid: 22527982. Pmcid: PMC4046310.
  • Pagán B, Isidro AA, Cruz ML, Ren Y, Coppola D, Wu J, Appleyard CB. Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model. World J Gastroenterol. 2011 Nov.17(44):4858-4866. Pubmedid: 22171126. Pmcid: PMC3235628.
  • Uronis JM, Arthur JC, Keku T, Fodor A, Carroll IM, Cruz ML, Appleyard CB, Jobin C. Gut microbial diversity is reduced by the probiotic VSL#3 and correlates with decreased TNBS-induced colitis. Inflamm Bowel Dis. 2011 Jan.17(1):289-297. Pubmedid: 20564535. Pmcid: PMC2953593.
  • Appleyard CB, Cruz ML, Isidro AA, Arthur JC, Jobin C, De Simone C. Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer. Am J Physiol Gastrointest Liver Physiol. 2011 Dec.301(6):G1004-G1013. Pubmedid: 21903764. Pmcid: PMC3233787.
  • Pagán B, Isidro AA, Coppola D, Chen Z, Ren Y, Wu J, Appleyard CB. Effect of a neurokinin-1 receptor antagonist in a rat model of colitis-associated colon cancer. Anticancer Res. 2010 Sep.30(9):3345-3353. Pubmedid: 20944107. Pmcid: PMC3733557.
  • Appleyard CB, Morales M, Santiago C. Chronic inflammation alters the contribution of neurokinin receptor subtypes to epithelial function in rat colon. Digest Dis Sci. 2008 Jan.53(1):220-228. Pubmedid: 17510797.
  • Santiago C, Pagán B, Isidro AA, Appleyard CB. Prolonged chronic inflammation progresses to dysplasia in a novel rat model of colitis-associated colon cancer. Cancer Res. 2007 Nov.67(22):10766-10773. Pubmedid: 18006820.
  • Rivera E, Flores I, Rivera E, Appleyard CB. Molecular profiling of a rat model of colitis: validation of known inflammatory genes and identification of novel disease-associated targets. Inflamm Bowel Dis. 2006 Oct.12(10):950-966. Pubmedid: 17012966.
  • Appleyard CB, Morales M, Percy WH. Regional variations in neurokinin receptor subtype contributions to muscularis mucosae and epithelial function in rat colon. Digest Dis Sci. 2006 Mar.51(3):506-516. Pubmedid: 16614960.
  • Rojas-Cartagena C, Flores I, Appleyard CB. Role of tumor necrosis factor receptors in an animal model of acute colitis. Cytokine. 2005 Oct.32(2):85-93. Pubmedid: 16213154.
  • Hernández GA, Valentín MR, Appleyard CB. Effect of bacterial chemotactic peptides on intestinal inflammation in animal models of acute and chronic "relapsed" colitis. Digest Dis Sci. 2005 Aug.50(8):1444-1453. Pubmedid: 16110833.
  • Appleyard CB, Hernández G, Rios-Bedoya CF. Basic epidemiology of inflammatory bowel disease in Puerto Rico. Inflamm Bowel Dis. 2004 Mar.10(2):106-111. Pubmedid: 15168809.
  • Hernández GA, Appleyard CB. Bacterial load in animal models of acute and chronic 'reactivated' colitis. Digestion. 2003.67(3):161-169. Pubmedid: 12853728.
  • Appleyard CB, Alvarez A, Percy WH. Temporal changes in colonic vascular architecture and inflammatory mediator levels in animal models of colitis. Digest Dis Sci. 2002 Sep.47(9):2007-2014. Pubmedid: 12353846.
  • Asfaha S, MacNaughton WK, Appleyard CB, Chadee K, Wallace JL. Persistent epithelial dysfunction and bacterial translocation after resolution of intestinal inflammation. Am J Physiol Gastrointest Liver Physiol. 2001 Sep.281(3):G635-G644. Pubmedid: 11518675.
  • Hathaway CA, Appleyard CB, Percy WH, Williams JL. Experimental colitis increases blood-brain barrier permeability in rabbits. Am J Physiol Gastrointest Liver Physiol. 1999 May.276(5 pt 1):G1174-G1180. Pubmedid: 10330008.
  • Appleyard CB, Williams JL, Hathaway CA, Percy WH. Temporal patterns of colonic blood flow and tissue damage in an animal model of colitis. Digest Dis Sci. 1999 Feb.44(2):431-438. Pubmedid: 10063934.
  • Swain MG, Appleyard CB, Wallace JL, Maric M. TNF-alpha facilitates inflammation-induced glucocorticoid secretion in rats with biliary obstruction. J Hepatol. 1997 Feb.26(2):361-368. Pubmedid: 9059958.
  • Davies NM, Røseth AG, Appleyard CB, McKnight W, Del Soldato P, Calignano A, Cirino G, Wallace JL. NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects. Aliment Pharmacol Ther. 1997 Feb.11(1):69-79. Pubmedid: 9042976.
  • Ferraz JG, Tigley AW, Appleyard CB, Wallace JL. TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in cirrhotic rats. Am J Physiol. 1997 Apr.272(4 Pt 1):G809-G814. Pubmedid: 9142912.
  • Appleyard CB, McCafferty DM, Tigley AW, Swain MG, Wallace JL. Tumor necrosis factor mediation of NSAID-induced gastric damage: role of leukocyte adherence. Am J Physiol. 1996 Jan.270(1 Pt 1):G42-G48. Pubmedid: 8772499.
  • Appleyard CB, Wallace JL. Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. Am J Physiol. 1995 Jul.269(1 Pt 1):G119-G125. Pubmedid: 7631788.
  • Wallace JL, Le T, Carter L, Appleyard CB, Beck PL. Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid. J Pharmacol Toxicol Methods. 1995 Aug.33(4):237-239. Pubmedid: 8527832.
  • Appleyard CB, Hillier K. Catabolism of platelet-activating factor by human colonic mucosa. Calcium dependence of the catabolizing enzymes. Biochem Pharmacol. 1992 Jun.43(12):2503-2509. Pubmedid: 1632809.