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Thomas Kelly Jr

TitleAssociate Professor
InstitutionUniversity of Arkansas for Medical Sciences
DepartmentPathology, College of Medicine
DivisionPathology Academic
Address318 Cancer Institute
200 South Cedar
Mail Slot # 845
Little Rock AR 72202
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    We are defining the mechanisms of cross-talk between activated fibroblasts and tumor associated macrophages that results in facilitation of breast cancer growth and progression that ultimately kills people with breast cancer. Specifically, we are investigating if activated fibroblasts are capable of converting immune activating macrophages (M1) to immune suppressive macrophages (M2). We are also investigating if immune suppressive macrophages can cause fibroblast activation. Steven R. Post and I have shown that SR-A mediated adhesion of macrophages to modified collagen results in PGE2 production and this PGE2 feeds back onto the macrophages and modulates cytokine production towards an M2 phenotype as evidenced by decreased TNF-alpha and increased IL-10 production (Nikolic et al, 2015, J. Leukocyte Biol. Feb 25. pii: jlb.2A1014-471RR. [Epub ahead of print]). We are currently looking to determine if adhesion of macrophages to FAP-modified collagen also promotes the M2 phenotype. I am an experienced PI with a broad background in cellular biology, and since 1992, I have focused my research on two matrix degrading enzymes—fibroblast activation protein-a (FAP) and heparanase—and their relationship to breast cancer. For over 20 years, I have led an independent research group that studies mechanisms of breast cancer metastasis that has been continuously funded by DoD-BCRP, NIH, and Industry grants and contracts. As a result, I am experienced in successfully administering research projects (e.g., staffing, research protections and budget) and collaborating with both basic and clinical scientists. My research has been published in prestigious cancer journals, such as Cancer Research and Blood. Through this research, my team and I have developed extensive experience with FAP biology in breast cancer.

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    American Society for Cell Biology
    American Association for Cancer Research
    Metastasis Research Society

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    1. Holthoff ER, Byrum SD, Mackintosh SG, Kelly T, Tackett AJ, Quick CM, Post SR. Vulvar squamous cell carcinoma aggressiveness is associated with differential expression of collagen and STAT1. Clin Proteomics. 2017; 14:40. PMID: 29225558.
      View in: PubMed
    2. Holthoff ER, Spencer H, Kelly T, Post SR, Quick CM. Pathologic features of aggressive vulvar carcinoma are associated with epithelial-mesenchymal transition. Hum Pathol. 2016 10; 56:22-30. PMID: 27327194; PMCID: PMC5021565 [Available on 10/01/17].
    3. Mazur A, Holthoff E, Vadali S, Kelly T, Post SR. Cleavage of Type I Collagen by Fibroblast Activation Protein-a Enhances Class A Scavenger Receptor Mediated Macrophage Adhesion. PLoS One. 2016; 11(3):e0150287. PMID: 26934296; PMCID: PMC4774960.
    4. Jeffus SK, Gehlot A, Holthoff E, Stone R, Spencer H, Kelly T, Post SR, Quick CM. A fibromyxoid stromal response is associated with an infiltrative tumor morphology, perineural invasion, and lymph node metastasis in squamous cell carcinoma of the vulva. Am J Surg Pathol. 2015 Sep; 39(9):1226-33. PMID: 26274029; PMCID: PMC4538995.
    5. Holthoff ER, Jeffus SK, Gehlot A, Stone R, Erickson SW, Kelly T, Quick CM, Post SR. Perineural Invasion Is an Independent Pathologic Indicator of Recurrence in Vulvar Squamous Cell Carcinoma. Am J Surg Pathol. 2015 Aug; 39(8):1070-4. PMID: 25786085; PMCID: PMC4503485.
    6. Nikolic DM, Vadali S, He B, Ware J, Kelly T, Post SR. Prostaglandins produced during class A scavenger receptor-mediated macrophage adhesion differentially regulate cytokine production. J Leukoc Biol. 2015 May; 97(5):901-908. PMID: 25717147.
      View in: PubMed
    7. Rahal OM, Pabona JM, Kelly T, Huang Y, Hennings LJ, Prior RL, Al-Dwairi A, Simmen FA, Simmen RC. Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming. Carcinogenesis. 2013 Feb; 34(2):464-74. PMID: 23144318; PMCID: PMC3564444.
    8. Kelly T, Huang Y, Simms AE, Mazur A. Fibroblast activation protein-a: a key modulator of the microenvironment in multiple pathologies. Int Rev Cell Mol Biol. 2012; 297:83-116. PMID: 22608558.
      View in: PubMed
    9. Huang Y, Simms AE, Mazur A, Wang S, León NR, Jones B, Aziz N, Kelly T. Fibroblast activation protein-a promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis. 2011 Aug; 28(6):567-79. PMID: 21604185.
      View in: PubMed
    10. Sharma SG, Gokden M, McKenney JK, Phan DC, Cox RM, Kelly T, Gokden N. The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features. Appl Immunohistochem Mol Morphol. 2010 Dec; 18(6):494-8. PMID: 21102195.
      View in: PubMed
    11. Monzavi-Karbassi B, Hine RJ, Stanley JS, Ramani VP, Carcel-Trullols J, Whitehead TL, Kelly T, Siegel ER, Artaud C, Shaaf S, Saha R, Jousheghany F, Henry-Tillman R, Kieber-Emmons T. Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells. Int J Oncol. 2010 Sep; 37(3):615-22. PMID: 20664930; PMCID: PMC3267577.
    12. Kelly T, Suva LJ, Nicks KM, MacLeod V, Sanderson RD. Tumor-derived syndecan-1 mediates distal cross-talk with bone that enhances osteoclastogenesis. J Bone Miner Res. 2010 Jun; 25(6):1295-304. PMID: 20200931; PMCID: PMC3148092.
    13. Galanzha EI, Shashkov EV, Kelly T, Kim JW, Yang L, Zharov VP. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat Nanotechnol. 2009 Dec; 4(12):855-60. PMID: 19915570; PMCID: PMC3663137.
    14. Naito A, Cook CC, Mizumachi T, Wang M, Xie CH, Evans TT, Kelly T, Higuchi M. Progressive tumor features accompany epithelial-mesenchymal transition induced in mitochondrial DNA-depleted cells. Cancer Sci. 2008 Aug; 99(8):1584-8. PMID: 18754870; PMCID: PMC2535852.
    15. Mueller S, Artym V, and Kelly. T. The Cancer Degradome - Proteases in Cancer Biology, Eds: Ed. D. Edwards, G. Hoyer-Hansen, F. Blasi, and B. F. Sloane. Invadopodia: Interface for invasion. 2008; 403-431.
    16. Kelly T, Coleman EA, Fifer E, Burns E, Orr C, and Nicholas, RW . Partners in research: benefits of a summer research program. Journal of Cancer Education. 2006; 21:243-247. 2006; 21:243-247.
    17. Sanderson RD, Yang Y, Kelly T, MacLeod V, Dai Y, Theus A. Enzymatic remodeling of heparan sulfate proteoglycans within the tumor microenvironment: growth regulation and the prospect of new cancer therapies. J Cell Biochem. 2005 Dec 01; 96(5):897-905. PMID: 16149080.
      View in: PubMed
    18. Monzavi-Karbassi B, Whitehead TL, Jousheghany F, Artaud C, Hennings L, Shaaf S, Slaughter A, Korourian S, Kelly T, Blaszczyk-Thurin M, Kieber-Emmons T. Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer. Int J Cancer. 2005 Nov 10; 117(3):398-408. PMID: 15906360.
      View in: PubMed
    19. Zharov VP, Galitovskaya EN, Johnson C, Kelly T. Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy. Lasers Surg Med. 2005 Sep; 37(3):219-26. PMID: 16175635.
      View in: PubMed
    20. Kelly T, Suva LJ, Huang Y, Macleod V, Miao HQ, Walker RC, Sanderson RD. Expression of heparanase by primary breast tumors promotes bone resorption in the absence of detectable bone metastases. Cancer Res. 2005 Jul 01; 65(13):5778-84. PMID: 15994953.
      View in: PubMed
    21. Kelly T. Fibroblast activation protein-alpha and dipeptidyl peptidase IV (CD26): cell-surface proteases that activate cell signaling and are potential targets for cancer therapy. Drug Resist Updat. 2005 Feb-Apr; 8(1-2):51-8. PMID: 15939342.
      View in: PubMed
    22. Yang Y, Macleod V, Bendre M, Huang Y, Theus AM, Miao HQ, Kussie P, Yaccoby S, Epstein J, Suva LJ, Kelly T, Sanderson RD. Heparanase promotes the spontaneous metastasis of myeloma cells to bone. Blood. 2005 Feb 01; 105(3):1303-9. PMID: 15471949.
      View in: PubMed
    23. Sanderson RD, Yang Y, Suva LJ, Kelly T. Heparan sulfate proteoglycans and heparanase--partners in osteolytic tumor growth and metastasis. Matrix Biol. 2004 Oct; 23(6):341-52. PMID: 15533755.
      View in: PubMed
    24. Huang Y, Wang S, Kelly T. Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer. Cancer Res. 2004 Apr 15; 64(8):2712-6. PMID: 15087384.
      View in: PubMed
    25. Kelly T, Miao HQ, Yang Y, Navarro E, Kussie P, Huang Y, MacLeod V, Casciano J, Joseph L, Zhan F, Zangari M, Barlogie B, Shaughnessy J, Sanderson RD. High heparanase activity in multiple myeloma is associated with elevated microvessel density. Cancer Res. 2003 Dec 15; 63(24):8749-56. PMID: 14695190.
      View in: PubMed
    26. Chen WT, Kelly T. Seprase complexes in cellular invasiveness. Cancer Metastasis Rev. 2003 Jun-Sep; 22(2-3):259-69. PMID: 12785000.
      View in: PubMed
    27. Goodman JD, Rozypal TL, Kelly T. Seprase, a membrane-bound protease, alleviates the serum growth requirement of human breast cancer cells. Clin Exp Metastasis. 2003; 20(5):459-70. PMID: 14524536.
      View in: PubMed
    28. Chen WT, Kelly T, Ghersi G. DPPIV, seprase, and related serine peptidases in multiple cellular functions. Curr Top Dev Biol. 2003; 54:207-32. PMID: 12696751.
      View in: PubMed
    29. Hovdenak N, Wang J, Sung CC, Kelly T, Fajardo LF, Hauer-Jensen M. Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer. Int J Radiat Oncol Biol Phys. 2002 Jul 15; 53(4):919-27. PMID: 12095558.
      View in: PubMed
    30. Kelly T, Børset M, Abe E, Gaddy-Kurten D, Sanderson RD. Matrix metalloproteinases in multiple myeloma. Leuk Lymphoma. 2000 Apr; 37(3-4):273-81. PMID: 10752979.
      View in: PubMed
    31. Kelly T. Evaluation of seprase activity. Clin Exp Metastasis. 1999 Feb; 17(1):57-62. PMID: 10390148.
      View in: PubMed
    32. Kaushal GP, Xiong X, Athota AB, Rozypal TL, Sanderson RD, Kelly T. Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9. Br J Haematol. 1999 Feb; 104(2):365-73. PMID: 10050721.
      View in: PubMed
    33. Kelly T, Kechelava S, Rozypal TL, West KW, Korourian S. Seprase, a membrane-bound protease, is overexpressed by invasive ductal carcinoma cells of human breast cancers. Mod Pathol. 1998 Sep; 11(9):855-63. PMID: 9758365.
      View in: PubMed
    34. Kelly T, Yan Y, Osborne RL, Athota AB, Rozypal TL, Colclasure JC, Chu WS. Proteolysis of extracellular matrix by invadopodia facilitates human breast cancer cell invasion and is mediated by matrix metalloproteinases. Clin Exp Metastasis. 1998 Aug; 16(6):501-12. PMID: 9872598.
      View in: PubMed
    35. Dhodapkar MV, Kelly T, Theus A, Athota AB, Barlogie B, Sanderson RD. Elevated levels of shed syndecan-1 correlate with tumour mass and decreased matrix metalloproteinase-9 activity in the serum of patients with multiple myeloma. Br J Haematol. 1997 Nov; 99(2):368-71. PMID: 9375756.
      View in: PubMed
    36. Monsky WL, Lin CY, Aoyama A, Kelly T, Akiyama SK, Mueller SC, Chen WT. A potential marker protease of invasiveness, seprase, is localized on invadopodia of human malignant melanoma cells. Cancer Res. 1994 Nov 01; 54(21):5702-10. PMID: 7923219.
      View in: PubMed
    37. Kelly T, Mueller SC, Yeh Y, Chen WT. Invadopodia promote proteolysis of a wide variety of extracellular matrix proteins. J Cell Physiol. 1994 Feb; 158(2):299-308. PMID: 8106567.
      View in: PubMed
    38. Chen WT, Lee CC, Goldstein L, Bernier S, Liu CH, Lin CY, Yeh Y, Monsky WL, Kelly T, Dai M, et al. Membrane proteases as potential diagnostic and therapeutic targets for breast malignancy. Breast Cancer Res Treat. 1994; 31(2-3):217-26. PMID: 7881100.
      View in: PubMed
    39. Monsky WL, Kelly T, Lin CY, Yeh Y, Stetler-Stevenson WG, Mueller SC, Chen WT. Binding and localization of M(r) 72,000 matrix metalloproteinase at cell surface invadopodia. Cancer Res. 1993 Jul 01; 53(13):3159-64. PMID: 8391388.
      View in: PubMed
    40. Mueller SC, Kelly T, Dai MZ, Dai HN, Chen WT. Dynamic cytoskeleton-integrin associations induced by cell binding to immobilized fibronectin. J Cell Biol. 1989 Dec; 109(6 Pt 2):3455-64. PMID: 2513332; PMCID: PMC2115959.
    41. Kelly, T. PhD Dissertation. 1988.
    42. Burridge K, Fath K, Kelly T, Nuckolls G, Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988; 4:487-525. PMID: 3058164.
      View in: PubMed
    43. Kelly T, Molony L, Burridge K. Purification of two smooth muscle glycoproteins related to integrin. Distribution in cultured chicken embryo fibroblasts. J Biol Chem. 1987 Dec 15; 262(35):17189-99. PMID: 3500174.
      View in: PubMed
    44. Burridge K, Molony L, Kelly T. Adhesion plaques: sites of transmembrane interaction between the extracellular matrix and the actin cytoskeleton. J Cell Sci Suppl. 1987; 8:211-29. PMID: 3332661.
      View in: PubMed
    45. Burridge K, Kelly T, Connell L. Proteins involved in the attachment of actin to the plasma membrane. Philos Trans R Soc Lond B Biol Sci. 1982 Nov 04; 299(1095):291-9. PMID: 6129663.
      View in: PubMed
    46. Burridge K, Kelly T, Mangeat P. Nonerythrocyte spectrins: actin-membrane attachment proteins occurring in many cell types. J Cell Biol. 1982 Nov; 95(2 Pt 1):478-86. PMID: 6183274; PMCID: PMC2112974.
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