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Kathleen L. O'Connor, PhD

Connect

859-323-7534
kloconnor@uky.edu
HKRB 344

Positions

  • Professor, Molecular and Cellular Biochemistry
  • Associate Director of Cancer Education and Mentoring, Markey Cancer Center
  • Director, Markey Science Training in Research, Oncology, Networking and professional Growth (STRONG) Scholars Program
  • Director, Markey STRONG Post-baccalaureate Fellows Program

College Unit(s)

Other Affiliation(s)
  • Markey Cancer Center
  • MD/PhD Program Mentor

Biography and Education

Education

B.S., James Madison University, 1988

Ph.D., Case Western Reserve University, 1996

Post-doctoral training, Harvard Medical School, 2001

Research

My research focuses on how integrin signaling promotes carcinoma invasion and metastasis with special emphasis on the integrin 伪6尾4. Integrin 伪6尾4 confers an invasive and metastatic phenotype in many types of carcinomas, including triple-receptor negative breast cancer (TNBC). Dissecting the pathways altered by integrin 伪6尾4 has given and will continue to contribute great insight into the processes that perpetuate an invasive and metastatic phenotype. I originally discovered links between integrin signaling and the cAMP pathway (JCB, 1998; JBC, 2001), and also determined that integrin 伪6尾4 could stimulate the small GTPase RhoA leading to lamellae formation (JCB, 2000; Oncogene 2013). We have further expanded our work to include investigations on how integrin 伪6尾4 modifies the transcriptome toward an invasion signature. Through these studies, we have identified the first transcriptional targets for NFAT1 (Oncogene 2005) and NFAT5 (JBC 2009) in cancer and found that integrin 伪6尾4 can stimulate select demethylation of the promoters of pro-metastatic genes, including S100A4/metastasin (JBC 2009), amphiregulin and epiregulin (JBC 2015). Our work on how integrin 伪6尾4 mediates promoter DNA demethylation uncovered a novel function for the integrin in regulating DNA repair. We find that the integrin stimulates and utilizes base excision repair in active DNA demethylation. We also found that the ability to stimulate DNA repair extends also to nucleotide excision repair (Sci Rep 2017) and non-homologous end joining (BioRxiv, 2019). Our overarching long-term goal is to determine how integrin 伪6尾4 drives the aggressive properties of TNBC so that this information can be used to guide precision medicine for TNBC.

Selected Publications

  1. Chen M, Marrs B, Qi L, Knifley T, Weiss HL, D鈥橭razio JA, and O鈥機onnor KL. Integrin 伪6尾4 signals through DNA damage response pathway to sensitize breast cancer cells to cisplatin. Front. Oncol. 12:1043538. 2022.  doi: 10.3389/fonc.2022.1043538
  2. Qi L, Chen M, Knifley T, and O鈥機onnor KL. Integrin 伪6尾4 requires plectin binding and vimentin to drive adhesion complex distribution and invasive growth. Journal of Cell Science, 15;135(2):jcs258471, 2022. PMCID: PMC8917354. PMID: 34897465.
  3. Qi L, Knifley T, Piecoro DW, Rychahou P, Wu J, O鈥機onnor KL, Chen M. Spontaneous Metastasis Assays Using A549 Lung Cancer Cells. Bio-protocol. 2020 April; 10(7):3579. doi: 10.21769/BioProtoc.3579.
  4. O'Connor KL. J Cancer Educ. 2020 Feb;35(1):205-209. doi: 10.1007/s13187-019-01514-5. PubMed PMID: 30887313; PubMed Central PMCID: PMC6751031.
  5. Huang X, Ye Q, Chen M, Li A, Mi W, Fang Y, Zaytseva YY, O'Connor KL, Vander Kooi CW, Liu S, She QB. Nat Commun. 2019 Aug 16;10(1):3708. doi: 10.1038/s41467-019-11580-4. PubMed PMID: 31420553; PubMed Central PMCID: PMC6697747.
  6. Harper NW, Hodges KB, Stewart RL, Wu J, Huang B, O'Connor KL, Romond EH. Clin Breast Cancer. 2019 Aug;19(4):e495-e500. doi: 10.1016/j.clbc.2019.05.009. Epub 2019 May 24. PubMed PMID: 31208874; PubMed Central PMCID: PMC6693323.
  7. Liu L, Qi L, Knifley T, Piecoro DW, Rychahou P, Liu J, Mitov MI, Martin J, Wang C, Wu J, Weiss HL, Butterfield DA, Evers BM, O'Connor KL, Chen M.J Biol Chem.2019 May 3;294(18):7516-7527. doi: 10.1074/jbc.RA118.004365. Epub 2019 Mar 18. PubMed PMID: 30885944; PubMed Central PMCID: PMC6509482.
  8. Xiong G, Stewart RL, Chen J, Gao T, Scott TL, Samayoa LM, O'Connor K, Lane AN, Xu R. Nat Commun. 2018 Oct 26;9(1):4456. doi: 10.1038/s41467-018-06893-9. PubMed PMID: 30367042; PubMed Central PMCID: PMC6203834.
  9. Carpenter BL, Liu J, Qi L, Wang C, O'Connor KL. Sci Rep. 2017 Jul 21;7(1):6174. doi: 10.1038/s41598-017-06351-4. PubMed PMID: 28733611; PubMed Central PMCID: PMC5522472.
  10. Stewart RL, O'Connor KL.  Hum Pathol. 2017 Mar;61:223-224. doi: 10.1016/j.humpath.2016.09.032. Epub 2016 Nov 2. PubMed PMID: 27816722.

  11. Stewart RL, West D, Wang C, Weiss HL, Gal T, Durbin EB, O'Connor W, Chen M, O'Connor KL.  Hum Pathol. 2016 Aug;54:174-83. doi: 10.1016/j.humpath.2016.04.003. Epub 2016 Apr 20. PubMed PMID: 27107458; PubMed Central PMCID: PMC4938774.

  12. Stewart RL, Carpenter BL, West DS, Knifley T, Liu L, Wang C, Weiss HL, Gal TS, Durbin EB, Arnold SM, O'Connor KL, Chen M.  Oncotarget. 2016 Jun 7;7(23):34630-42. doi: 10.18632/oncotarget.8969. PubMed PMID: 27127879; PubMed Central PMCID: PMC5085181.

        

  13. Carpenter BL, Chen M, Knifley T, Davis KA, Harrison SM, Stewart RL, O'Connor KL.  J Biol Chem. 2015 Nov 6;290(45):27228-38. doi: 10.1074/jbc.M115.686873. Epub 2015 Sep 17. PubMed PMID: 26381405; PubMed Central PMCID: PMC4646402.

        

  14. Stewart RL, O'Connor KL.  Lab Invest. 2015 Sep;95(9):976-86. doi: 10.1038/labinvest.2015.82. Epub 2015 Jun 29. Review. PubMed PMID: 26121317; PubMed Central PMCID: PMC4554527.

       

  15. Zaytseva YY, Elliott VA, Rychahou P, Mustain WC, Kim JT, Valentino J, Gao T, O'Connor KL, Neltner JM, Lee EY, Weiss HL, Evers BM. Carcinogenesis. 2014 Jun;35(6):1341-51. doi: 10.1093/carcin/bgu042. Epub 2014 Feb 7. PubMed PMID: 24510238; PubMed Central PMCID: PMC4043242.

       

  16. Yin Y, Deng X, Liu Z, Baldwin LA, Lefringhouse J, Zhang J, Hoff JT, Erfani SF, Rucker EB 3rd, O'Connor K, Liu C, Wu Y, Zhou BP, Yang XH.  Cell Cycle. 2014;13(17):2707-22. doi: 10.4161/15384101.2015.945823. PubMed PMID: 25486358; PubMed Central PMCID: PMC4614859.

        

  17. Chen M, Knifley T, Subramanian T, Spielmann HP, O'Connor KL.  PLoS One. 2014 Feb 26;9(2):e89892. doi: 10.1371/journal.pone.0089892. eCollection 2014. PubMed PMID: 24587105; PubMed Central PMCID: PMC3935959.

        

  18. Harrison SM, Knifley T, Chen M, O'Connor KL.  BMC Cancer. 2013 Oct 27;13:501. doi: 10.1186/1471-2407-13-501. PubMed PMID: 24160245; PubMed Central PMCID: PMC3819718.

        

  19. Chen M, Bresnick AR, O'Connor KL.  Oncogene. 2013 Aug 8;32(32):3754-64. doi: 10.1038/onc.2012.383. Epub 2012 Sep 10. PubMed PMID: 22964635; PubMed Central PMCID: PMC3525797.

        

  20. O'Connor K, Chen M.  Small GTPases. 2013 Jul-Sep;4(3):141-7. doi: 10.4161/sgtp.25131. Epub 2013 Jun 10. Review. PubMed PMID: 24025634; PubMed Central PMCID: PMC3976970.

        

  21. Lee S, Qiao J, Paul P, O'Connor KL, Evers MB, Chung DH. Oncotarget. 2012 Dec;3(12):1576-87. PubMed PMID: 23211542; PubMed Central PMCID: PMC3681496.

        

  22. Zaytseva YY, Rychahou PG, Gulhati P, Elliott VA, Mustain WC, O'Connor K, Morris AJ, Sunkara M, Weiss HL, Lee EY, Evers BM.  Cancer Res. 2012 Mar 15;72(6):1504-17. doi: 10.1158/0008-5472.CAN-11-4057. Epub 2012 Jan 19. PubMed PMID: 22266115; PubMed Central PMCID: PMC3596828.

        

  23. O'Connor KL, Chen M, Towers LN.  Am J Physiol Cell Physiol. 2012 Feb 1;302(3):C605-14. doi: 10.1152/ajpcell.00095.2011. Epub 2011 Nov 2. PubMed PMID: 22049212; PubMed Central PMCID: PMC3287157.

        

  24. Chen M, Sastry SK, O'Connor KL.  Am J Physiol Cell Physiol. 2011 May;300(5):C1155-63. doi: 10.1152/ajpcell.00407.2010. Epub 2011 Feb 2. PubMed PMID: 21289293.

  25. Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, Lee EY, Weiss HL, O'Connor KL, Gao T, Evers BM.  Cancer Res. 2011 May 1;71(9):3246-56. doi: 10.1158/0008-5472.CAN-10-4058. Epub 2011 Mar 23. PubMed PMID: 21430067; PubMed Central PMCID: PMC3085654.

        

  26. Murillo CA, Woodside KJ, Guo Q, Zhang S, O'Connor KL, Hunter GC.  J Surg Res. 2009 Jul;155(1):157-64. doi: 10.1016/j.jss.2008.08.005. Epub 2008 Sep 7. PubMed PMID: 19394653.

  27. Paulucci-Holthauzen AA, Vergara LA, Bellot LJ, Canton D, Scott JD, O'Connor KL.  J Biol Chem. 2009 Feb 27;284(9):5956-67. doi: 10.1074/jbc.M805606200. Epub 2008 Dec 23. PubMed PMID: 19106088; PubMed Central PMCID: PMC2645839.

        

  28. Chen M, Sinha M, Luxon BA, Bresnick AR, O'Connor KL.  J Biol Chem. 2009 Jan 16;284(3):1484-94. doi: 10.1074/jbc.M803997200. Epub 2008 Nov 14. PubMed PMID: 19011242; PubMed Central PMCID: PMC2615501.

        

  29. Cruz-Monserrate Z, O'Connor KL.  Neoplasia. 2008 May;10(5):408-17. PubMed PMID: 18472958; PubMed Central PMCID: PMC2373869.

        

  30. Cruz-Monserrate Z, Qiu S, Evers BM, O'Connor KL.  Mod Pathol. 2007 Jun;20(6):656-67. Epub 2007 Apr 13. PubMed PMID: 17415382; PubMed Central PMCID: PMC4697742.

        

  31. Chen M, Towers LN, O'Connor KL.  Am J Physiol Cell Physiol. 2007 May;292(5):C1927-33. PubMed PMID: 17496233.

  32. Li J, O'Connor KL, Cheng X, Mei FC, Uchida T, Townsend CM Jr, Evers BM.  Mol Endocrinol. 2007 Jan;21(1):159-71. Epub 2006 Oct 26. PubMed PMID: 17068197.

  33. Paulucci-Holthauzen AA, O'Connor KL.  Anal Biochem. 2006 Aug 15;355(2):175-82. Epub 2006 Jun 19. PubMed PMID: 16842735.

  34. Chen M, O'Connor KL.  Oncogene. 2005 Jul 28;24(32):5125-30. PubMed PMID: 15897878.

  35. Li J, O'Connor KL, Greeley GH Jr, Blackshear PJ, Townsend CM Jr, Evers BM.  J Biol Chem. 2005 Mar 4;280(9):8351-7. Epub 2004 Dec 28. PubMed PMID: 15623535.

  36. Li J, O'Connor KL, Hellmich MR, Greeley GH Jr, Townsend CM Jr, Evers BM.  J Biol Chem. 2004 Jul 2;279(27):28466-74. Epub 2004 Apr 27. PubMed PMID: 15123666.

  37. Farrow B, Rychahou P, O'Connor KL, Evers BM.  J Gastrointest Surg. 2003 Nov;7(7):864-70. PubMed PMID: 14592659.

  38. Farrow B, Rychahou P, Murillo C, O'connor KL, Iwamura T, Evers BM.  Surgery. 2003 Aug;134(2):197-205. PubMed PMID: 12947318.

  39. Farrow B, O'Connor KL, Hashimoto K, Iwamura T, Evers BM.  Surgery. 2003 Aug;134(2):206-12. PubMed PMID: 12947319.

  40. O'Connor KL, Mercurio AM.  J Biol Chem. 2001 Dec 21;276(51):47895-900. Epub 2001 Oct 17. PubMed PMID: 11606581.

  41. Mercurio AM, Bachelder RE, Chung J, O'Connor KL, Rabinovitz I, Shaw LM, Tani T.  J Mammary Gland Biol Neoplasia. 2001 Jul;6(3):299-309. Review. PubMed PMID: 11547899.

  42. Mercurio AM, Bachelder RE, Rabinovitz I, O'Connor KL, Tani T, Shaw LM.  Surg Oncol Clin N Am. 2001 Apr;10(2):313-28, viii-ix. Review. PubMed PMID: 11382589.

  43. O'Connor KL, Nguyen BK, Mercurio AM.  J Cell Biol. 2000 Jan 24;148(2):253-8. PubMed PMID: 10648558; PubMed Central PMCID: PMC2174290.

        

  44. O'Connor KL, Shaw LM, Mercurio AM.  J Cell Biol. 1998 Dec 14;143(6):1749-60. PubMed PMID: 9852165; PubMed Central PMCID: PMC2132981.

        

  45. Culp LA, Lin W, Kleinman NR, O'Connor KL, Lechner R.  J Histochem Cytochem. 1998 May;46(5):557-68. Review. PubMed PMID: 9562566.

  46. Culp LA, O'Connor KL, Lechner R. Principles of Medical Biology, Volume 7B. Bittar E, editor. Greenwich, CT: JAI Press; 1997. Chapter 25, Extracellular matrix adhesion: Biological, molecular and pathological mechanisms; p.573-607. 
  47. O'Connor KL, Culp LA. Biotechniques. 1994 Sep;17(3):502-6, 508-9. PubMed PMID: 7818904.
  48. O'Connor KL, Culp LA. Topological and quantitative analyses of early events in tumor formation using histochemically-tagged transformed 3T3 cells. Oncology reports. 1994; 1:869-896.

  49. Lin WC, O'Connor KL, Culp LA.  Br J Cancer. 1993 May;67(5):910-21. PubMed PMID: 8494724; PubMed Central PMCID: PMC1968424.

        

  50. Strayer DS, Jerng HH, O'Connor K.  Virology. 1991 Dec;185(2):585-95. PubMed PMID: 1660196.

  51. Heard HK, O'Connor K, Strayer DS.  J Immunol. 1990 May 15;144(10):3992-9. PubMed PMID: 2159037.

  52. Dendinger JE, O'Connor KL. Purification and characterization of a trypsin-like enzyme from the midgut gland of the Atlantic Blue Crab, Callinectes sapidus. Comp. Biochem. Physiol.. 1990; 95B:525-530.