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Salisbury, Travis

SundaramTravis Salisbury, PhD
Associate Professor

Research Statement

I have 12 years of experience in studies on regulation of gene expression in response to signaling. My work on regulated gene expression started during my postdoctoral training. My research identified that gonadotropin releasing hormone (GnRH), which signals through a G protein coupled receptor (GPCR), regulates gene expression by activating the transcriptional coactivator β-catenin. Finding that GPCR signaling regulated β- catenin activity was novel, because β-catenin had historically been associated with the developmental Wnt signaling pathway. Currently, I supervise an active laboratory, teach medical and graduate students and I was promoted to associate professor with tenure in 2015. My work remains focused on signal-regulated gene expression. Our recent studies have identified that the aryl hydrocarbon receptor (AHR), which is a ligandactivated transcription factor, responds to and mediates signaling pathways in breast cancer cells including insulin like growth factor 2 (IGF2), tumor necrosis factor (TNF) and adipokines. Evidence that IGF2, TNF, and adipokines signal through AHR is an important shift in its role, considering that AHR is best known for mediating the toxic and gene expression effects of the environmental toxicant TCDD

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Research focus.

Our research focus is on signaling mechanisms that control breast cancer. One project investigates targeting nutrient transport to suppress breast cancer in obesity. The premise for this project stems from clinical work showing that obesity significant increases breast cancer mortality, worsens breast cancer outcomes, renders tumors less responsive to cancer therapy and increases the rate of metastatic breast cancer. The signaling mechanisms by which obesity promotes breast cancer progression is an important knowledge gap. We hypothesize that paracrine and endocrine factors released by adipose tissue during obesity induce signaling in breast cancer cells that increases leucine absorption by cancer cells. In addition to being an essential amino acid that is required for protein synthesis, leucine can also induce and sustain oncogenic mTOR signaling in cancer. Thus, suppressing leucine uptake by cancer cells will not only starve tumor cells, but it will also reduce mTOR pathways that promote the growth and metastatic potential of cancer. Others and we have published that L-Type Amino Acid Transporter 1 (LAT1) is a critically important leucine transporter that is overexpressed in breast cancer. Others and we have published that suppressing LAT1 inhibits the growth of breast cancer cells. We have new data showing that adipose tissue secretes factors that induce LAT1 expression and activity in breast cancer cells. We therefore hypothesize that obesity promotes breast cancer by inducing LAT1 expression and activity in breast tumors. We are currently investigating the unique regulation of LAT1 in breast cancer during obesity.


Our second project involves targeting the aryl hydrocarbon receptor (AHR) to suppress breast cancer. The AHR is a ligand activated transcription factor. Others and we have shown that certain AHR ligands inhibit the growth and metastatic potential of breast cancer cells.  We recently published that the putative endogenous AHR ligand, ITE, reduces the JAG1-NOTCH1 pathway in triple negative breast cancer (TNBC) cells. The JAG1-NOTCH1 pathway is an embryonic pathway that upon being overactive induces and promotes breast cancer.  There are drugs in clinical trials to suppress the JAG1-NOTCH1 pathway for breast cancer therapy. However, our report is the first to show that an AHR ligand suppresses JAG1-NOTCH1 signaling in cancer. This new finding provides mechanistic evidence to suppress JAG1-NOTCH1 signaling in cancer with AHR ligands. We are currently investigating mechanisms by which ITE inhibits breast cancer growth by inhibiting cell cycle and the JAG1-NOTCH1 pathway.


Specific Projects:

  • Targeting cellular nutrient transport to suppress breast cancer during obesity.
  • Targeting the aryl hydrocarbon receptor to inhibit breast cancer
  • We use a variety of cell biology, molecular biology, gene knockdown, and genomic methods to study breast cancer.
  1. The Regulation and Function of the L-Type Amino Acid Transporter 1 (LAT1) in Cancer. Salisbury TB, Arthur S.Salisbury TB, et al.Int J Mol Sci. 2018 Aug 12;19(8):2373. doi: 10.3390/ijms19082373.Int J Mol Sci. 2018.PMID: 30103560Free PMC article.Review.
  2. Aryl hydrocarbon receptor (AHR) regulation of L-Type Amino Acid Transporter 1 (LAT-1) expression in MCF-7 and MDA-MB-231 breast cancer cells. Tomblin JK, Arthur S, Primerano DA, Chaudhry AR, Fan J, Denvir J, Salisbury TB.Tomblin JK, et al.Biochem Pharmacol. 2016 Apr 15;106:94-103. doi: 10.1016/j.bcp.2016.02.020. Epub 2016 Mar 2.Biochem Pharmacol. 2016.PMID: 26944194Free PMC article.
  3. Insulin/Insulin-like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms, and new blocking strategies. Salisbury TB, Tomblin JK.Salisbury TB, et al.Front Endocrinol (Lausanne). 2015 Feb 2;6:12. doi: 10.3389/fendo.2015.00012. eCollection 2015.Front Endocrinol (Lausanne). 2015.PMID: 25699021Free PMC article.Review.
  4. Endogenous aryl hydrocarbon receptor promotes basal and inducible expression of tumor necrosis factor target genes in MCF-7 cancer cells. Salisbury TB, Tomblin JK, Primerano DA, Boskovic G, Fan J, Mehmi I, Fletcher J, Santanam N, Hurn E, Morris GZ, Denvir J.Salisbury TB, et al.Biochem Pharmacol. 2014 Oct 1;91(3):390-9. doi: 10.1016/j.bcp.2014.06.015. Epub 2014 Jun 24.Biochem Pharmacol. 2014.PMID: 24971714Free PMC article.
  5. The putative endogenous AHR ligand ITE reduces JAG1 and associated NOTCH1 signaling in triple negative breast cancer cells. Piwarski SA, Thompson C, Chaudhry AR, Denvir J, Primerano DA, Fan J, Salisbury TB.Piwarski SA, et al.Biochem Pharmacol. 2020 Apr;174:113845. doi: 10.1016/j.bcp.2020.113845. Epub 2020 Feb 4.Biochem Pharmacol. 2020.PMID: 32032581
  6. Insulin like growth factor 2 regulation of aryl hydrocarbon receptor in MCF-7 breast cancer cells. Tomblin JK, Salisbury TB.Tomblin JK, et al.Biochem Biophys Res Commun. 2014 Jan 17;443(3):1092-6. doi: 10.1016/j.bbrc.2013.12.112. Epub 2013 Dec 28.Biochem Biophys Res Commun. 2014.PMID: 24380854Free PMC article.
  7. Welcoming beta-catenin to the gonadotropin-releasing hormone transcriptional network in gonadotropes. Salisbury TB, Binder AK, Nilson JH.Salisbury TB, et al.Mol Endocrinol. 2008 Jun;22(6):1295-303. doi: 10.1210/me.2007-0515. Epub 2008 Jan 24.Mol Endocrinol. 2008.PMID: 18218726Free PMC article.Review.
  8. Aryl hydrocarbon receptor ligands inhibit igf-ii and adipokine stimulated breast cancer cell proliferation. Salisbury TB, Morris GZ, Tomblin JK, Chaudhry AR, Cook CR, Santanam N.Salisbury TB, et al.ISRN Endocrinol. 2013 Sep 23;2013:104850. doi: 10.1155/2013/104850. eCollection 2013.ISRN Endocrinol. 2013.PMID: 24171117Free PMC article.
  9. GnRH-regulated expression of Jun and JUN target genes in gonadotropes requires a functional interaction between TCF/LEF family members and beta-catenin. Salisbury TB, Binder AK, Grammer JC, Nilson JH.Salisbury TB, et al.Mol Endocrinol. 2009 Mar;23(3):402-11. doi: 10.1210/me.2008-0370. Epub 2009 Jan 8.Mol Endocrinol. 2009.PMID: 19131506Free PMC article.
  10. In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-pentachlorodibenzofuran reduces growth and disrupts reproductive parameters in female rats. Salisbury TB, Marcinkiewicz JL.Salisbury TB, et al.Biol Reprod. 2002 Jun;66(6):1621-6. doi: 10.1095/biolreprod66.6.1621.Biol Reprod. 2002.PMID: 12021039
  11. Maximal activity of the luteinizing hormone beta-subunit gene requires beta-catenin. Salisbury TB, Binder AK, Grammer JC, Nilson JH.Salisbury TB, et al.Mol Endocrinol. 2007 Apr;21(4):963-71. doi: 10.1210/me.2006-0383. Epub 2007 Jan 23.Mol Endocrinol. 2007.PMID: 17244763

Lab personnel:

  • Chelsea Thompson, Research Associate II, BS, Ball State University
  • Cora Miracle, MD/PhD Candidate