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Rosalyn Irby
Title Associate Professor
Institution College of Medicine
Department Medicine
Address 500 University Drive Hershey PA 17033
Mailbox: H072
Telephone 7175311050
Email
Background
PREFERRED TITLE/ROLE:

Associate Professor of Medicine

GRADUATE PROGRAM AFFILIATIONS:

Cell and Molecular Biology, Integrative Biosciences, Molecular Medicine

EDUCATION:

B.S., Duke University
Ph.D., University of South Florida College of Medicine

NARRATIVE:

Investigation into the etiology of large granular lymphocyte (LGL) leukemia. We are looking for a transmissable viral component to LGL leukemia. There is data to support this theory, and we expect to isolate and characterize the virus that causes LGL leukemia. In addition, we are using microarray technology to create a fingerprint of LGL leukemia, and to relate it to rheumatoid arthritis. This will allow us to identify those genes that are responsible for the LGL leukemia phenotype, to determine a relationship between LGL leukemia and rheumatoid arthritis, and to test the response of both diseases to drug treatments.

Identification of the molecular basis for metastatic disease in colorectal cancer. For the past eight years I have been working on the Src oncogene and its role in colorectal cancer progression with an emphasis on metastasis. We have identified upstream activators and downstream targets of Src. The relationship of Src to other oncogenes and tumor suppressor genes, including osteopontin, Ras, p21, p53, and adenomatous polyposis coli (APC) have been studied. We have examined a number of phenotypic effects of Src, and are in the process of using novel Src specific inhibitors to determine the degree of metastatic inhibition they will exert in vivo. Current studies are being conducted to examine the effects of Src on tumor suppressor genes in both colon and breast cancer. The goal of these studies is to identify an effective target for chemotherapy.
Publications
1. Allen JE, Gallant JN, Dicker DT, Amin S, Irby RB, Sharma AK, El-Deiry WS. The Akt Inhibitor ISC-4 Synergizes with Cetuximab in 5-FU-Resistant Colon Cancer. PLoS One. 2013; 8(3):e59380.
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2. Irby RB, Kline CL. Par-4 as a potential target for cancer therapy. Expert Opin Ther Targets. 2013 Jan; 17(1):77-87.
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3. Nyland SB, Krissinger DJ, Clemente MJ, Irby RB, Baab KT, Jarbadan NR, Sokol L, Schaefer E, Liao J, Cuthbertson D, Epling-Burnette P, Paquette R, List AF, Maciejewski JP, Loughran TP. Seroreactivity to LGL leukemia-specific epitopes in aplastic anemia, myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria: results of a bone marrow failure consortium study. Leuk Res. 2012 May; 36(5):581-7.
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4. Kline CL, Irby RB. The pro-apoptotic protein Prostate Apoptosis Response Protein-4 (Par-4) can be activated in colon cancer cells by treatment with Src inhibitor and 5-FU. Apoptosis. 2011 Dec; 16(12):1285-94.
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5. Krishnegowda G, Prakasha Gowda AS, Tagaram HR, Carroll KF, Irby RB, Sharma AK, Amin S. Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway. Bioorg Med Chem. 2011 Oct 15; 19(20):6006-14.
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6. Sharma AK, Kline CL, Berg A, Amin S, Irby RB. The Akt inhibitor ISC-4 activates prostate apoptosis response protein-4 and reduces colon tumor growth in a nude mouse model. Clin Cancer Res. 2011 Jul 1; 17(13):4474-83.
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7. Irby RB. Epidermal growth factor receptor revisited: prognostic marker or target for therapy? Cancer Biol Ther. 2010 Sep; 10(5):422-4.
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8. House CD, Vaske CJ, Schwartz AM, Obias V, Frank B, Luu T, Sarvazyan N, Irby R, Strausberg RL, Hales TG, Stuart JM, Lee NH. Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res. 2010 Sep 1; 70(17):6957-67.
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9. Wang BD, Kline CL, Pastor DM, Olson TL, Frank B, Luu T, Sharma AK, Robertson G, Weirauch MT, Patierno SR, Stuart JM, Irby RB, Lee NH. Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network. Mol Cancer. 2010; 9:98.
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10. Pastor DM, Irby RB, Poritz LS. Tumor necrosis factor alpha induces p53 up-regulated modulator of apoptosis expression in colorectal cancer cell lines. Dis Colon Rectum. 2010 Mar; 53(3):257-63.
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11. Pastor DM, Poritz LS, Olson TL, Kline CL, Harris LR, Koltun WA, Chinchilli VM, Irby RB. Primary cell lines: false representation or model system? a comparison of four human colorectal tumors and their coordinately established cell lines. Int J Clin Exp Med. 2010; 3(1):69-83.
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12. Yang J, Liu X, Nyland SB, Zhang R, Ryland LK, Broeg K, Baab KT, Jarbadan NR, Irby R, Loughran TP. Platelet-derived growth factor mediates survival of leukemic large granular lymphocytes via an autocrine regulatory pathway. Blood. 2010 Jan 7; 115(1):51-60.
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13. Kline CL, Shanmugavelandy SS, Kester M, Irby RB. Delivery of PAR-4 plasmid in vivo via nanoliposomes sensitizes colon tumor cells subcutaneously implanted into nude mice to 5-FU. Cancer Biol Ther. 2009 Oct; 8(19):1831-7.
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14. Kline CL, Olson TL, Irby RB. Src activity alters alpha3 integrin expression in colon tumor cells. Clin Exp Metastasis. 2009; 26(2):77-87.
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15. Kline CL, Jackson R, Engelman R, Pledger WJ, Yeatman TJ, Irby RB. Src kinase induces tumor formation in the c-SRC C57BL/6 mouse. Int J Cancer. 2008 Jun 15; 122(12):2665-73.
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16. Shah MV, Zhang R, Irby R, Kothapalli R, Liu X, Arrington T, Frank B, Lee NH, Loughran TP. Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes. Blood. 2008 Aug 1; 112(3):770-81.
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17. Niu G, Wright KL, Ma Y, Wright GM, Huang M, Irby R, Briggs J, Karras J, Cress WD, Pardoll D, Jove R, Chen J, Yu H. Role of Stat3 in regulating p53 expression and function. Mol Cell Biol. 2005 Sep; 25(17):7432-40.
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18. Cook AC, Tuck AB, McCarthy S, Turner JG, Irby RB, Bloom GC, Yeatman TJ, Chambers AF. Osteopontin induces multiple changes in gene expression that reflect the six "hallmarks of cancer" in a model of breast cancer progression. Mol Carcinog. 2005 Aug; 43(4):225-36.
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19. Irby RB, Malek RL, Bloom G, Tsai J, Letwin N, Frank BC, Verratti K, Yeatman TJ, Lee NH. Iterative microarray and RNA interference-based interrogation of the SRC-induced invasive phenotype. Cancer Res. 2005 Mar 1; 65(5):1814-21.
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20. Irby RB, McCarthy SM, Yeatman TJ. Osteopontin regulates multiple functions contributing to human colon cancer development and progression. Clin Exp Metastasis. 2004; 21(6):515-23.
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21. Agrawal D, Chen T, Irby R, Quackenbush J, Chambers AF, Szabo M, Cantor A, Coppola D, Yeatman TJ. Osteopontin identified as colon cancer tumor progression marker. C R Biol. 2003 Oct-Nov; 326(10-11):1041-3.
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22. Chen T, Yang I, Irby R, Shain KH, Wang HG, Quackenbush J, Coppola D, Cheng JQ, Yeatman TJ. Regulation of caspase expression and apoptosis by adenomatous polyposis coli. Cancer Res. 2003 Aug 1; 63(15):4368-74.
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23. Lopez D, Irby RB, McLean MP. Peroxisome proliferator-activated receptor alpha induces rat sterol carrier protein x promoter activity through two peroxisome proliferator-response elements. Mol Cell Endocrinol. 2003 Jul 31; 205(1-2):169-84.
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24. Malek RL, Irby RB, Guo QM, Lee K, Wong S, He M, Tsai J, Frank B, Liu ET, Quackenbush J, Jove R, Yeatman TJ, Lee NH. Identification of Src transformation fingerprint in human colon cancer. Oncogene. 2002 Oct 17; 21(47):7256-65.
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25. Irby RB, Yeatman TJ. Increased Src activity disrupts cadherin/catenin-mediated homotypic adhesion in human colon cancer and transformed rodent cells. Cancer Res. 2002 May 1; 62(9):2669-74.
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26. Agrawal D, Chen T, Irby R, Quackenbush J, Chambers AF, Szabo M, Cantor A, Coppola D, Yeatman TJ. Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst. 2002 Apr 3; 94(7):513-21.
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27. Teng S, Sun J, Irby R, Hamilton AD, Sebti S, Yeatman TJ. v-Src transformation is mediated through farnesylated proteins. J Surg Res. 2001 Aug; 99(2):343-6.
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28. Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci U S A. 2001 Jun 19; 98(13):7319-24.
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29. Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene. 2000 Nov 20; 19(49):5636-42.
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30. Irby RB, Mao W, Coppola D, Kang J, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ. Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet. 1999 Feb; 21(2):187-90.
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31. Paredes-Zaglul A, Kang JJ, Essig YP, Mao W, Irby R, Wloch M, Yeatman TJ. Analysis of colorectal cancer by comparative genomic hybridization: evidence for induction of the metastatic phenotype by loss of tumor suppressor genes. Clin Cancer Res. 1998 Apr; 4(4):879-86.
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32. Mao W, Irby R, Coppola D, Fu L, Wloch M, Turner J, Yu H, Garcia R, Jove R, Yeatman TJ. Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. Oncogene. 1997 Dec 18; 15(25):3083-90.
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33. Irby R, Mao W, Coppola D, Jove R, Gamero A, Cuthbertson D, Fujita DJ, Yeatman TJ. Overexpression of normal c-Src in poorly metastatic human colon cancer cells enhances primary tumor growth but not metastatic potential. Cell Growth Differ. 1997 Dec; 8(12):1287-95.
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34. McLean MP, Warden KJ, Sandhoff TW, Irby RB, Hales DB. Altered ovarian sterol carrier protein expression in the pregnant streptozotocin-treated diabetic rat. Biol Reprod. 1996 Jul; 55(1):38-46.
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35. McLean MP, Billheimer JT, Warden KJ, Irby RB. Prostaglandin F2 alpha mediates ovarian sterol carrier protein-2 expression during luteolysis. Endocrinology. 1995 Nov; 136(11):4963-72.
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36. McLean MP, Billheimer JT, Warden KJ, Irby RB. Differential expression of hepatic sterol carrier proteins in the streptozotocin-treated diabetic rat. Endocrinology. 1995 Aug; 136(8):3360-8.
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37. McLean MP, Nanjo K, Irby RB, Warden KJ, Billheimer JT. Reduced hepatic sterol carrier protein-2 expression in the streptozotocin treated diabetic rat. Endocrine. 1995 Aug; 3(8):563-71.
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38. Irby RB, Adair WL. Intermediates in the folic acid biosynthetic pathway are incorporated into molybdopterin the yeast, Pichia canadensis. J Biol Chem. 1994 Sep 30; 269(39):23981-7.
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39. Irby R, Adair WL. Enzymatic preparation of [2,4,5,6,8-14C, 5'-3H]guanosine for use in biosynthetic studies of pterinoid and flavin compounds. Anal Biochem. 1994 May 1; 218(2):413-6.
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40. Cochrane BJ, Irby RB, Snell TW. Effects of copper and tributyltin on stress protein abundance in the rotifer Brachionus plicatilis. Comp Biochem Physiol C. 1991; 98(2-3):385-90.
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41. Irby R. PSRO, NHI, HMO'S--the doctor's dilemma. Va Med Mon (1918). 1974 May; 101(5):362-5.
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42. Van Valkenburgh WG, Georges LP, Irby R. Aortic insufficiency and pelvospondylitis in a seropositive female with rheumatoid nodules. Arthritis Rheum. 1972 Sep-Oct; 15(5):544-52.
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43. Melton JW, Irby R. Multicentric reticulohistiocytosis. Arthritis Rheum. 1972 Mar-Apr; 15(2):221-6.
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44. Cooke CL, Owen DS, Irby R, Toone E. Gonococcal arthritis. A survey of 54 cases. JAMA. 1971 Jul 12; 217(2):204-5.
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45. Waller M, Moon JH, Irby R, Toone EC. The effect of 1-phenylalanine mustard on anti-globulin antibodies in multiple myeloma. Clin Exp Immunol. 1971 Jan; 8(1):91-100.
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46. Owen DS, Irby R, Toone E. Relapsing polychondritis with aortic involvement. Arthritis Rheum. 1970 Nov-Dec; 13(6):877-81.
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47. Owen DS, Toone EC, Irby R. Management of gouty arthritis and hyperuricemia. GP. 1968 Oct; 38(4):133-8.
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48. Irby R, Hume DM. Joint changes observed following renal transplants. Clin Orthop Relat Res. 1968 Mar-Apr; 57:101-14.
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49. Owen DS, Toone E, Irby R. Coexistent rheumatoid arthritis and chronic tophaceous gout. JAMA. 1966 Sep 19; 197(12):953-6.
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50. WALLER M, IRBY R, MULLINAX F, TOONE EC. CONNECTIVE-TISSUE DISEASE AND RHEUMATOID FACTORS IN PATIENTS WITH RENAL TRANSPLANTS. N Engl J Med. 1965 Jul 1; 273:12-8.
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51. CALABAR SWELLING IN VIRGINIA. Va Med Mon (1918). 1965 May; 92:226-8.
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52. IRBY R, TOONE EC, WITTKAMP B, WIESINGER H. CATARACTS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH CORTICOSTEROIDS. GP. 1964 Jan; 29:92-5.
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53. IRBY R. Anti-inflammatory agents in the treatment of connective tissue diseases. Va Med Mon (1918). 1963 Apr; 90:169-73.
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54. WALLER MV, DECKER B, TOONE EC, IRBY R. Evaluation of rheumatoid factor tests. Arthritis Rheum. 1961 Dec; 4:579-91.
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55. TOONE EC, IRBY R, PIERCE EL. The L.E. cell in rheumatoid arthritis. Am J Med Sci. 1960 Nov; 240:599-608.
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56. IRBY R, ADAMS RA, TOONE EC. Peripheral neuritis associated with rheumatoid arthritis. Arthritis Rheum. 1958 Feb; 1(1):44-53.
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57. TOONE EC, IRBY R. An evaluation of phenylbutazone (butazolidin) in the treatment of gout, rheumatoid spondylitis, rheumatoid arthritis and other conditions of the musculoskeletal system. South Med J. 1957 May; 50(5):655-62.
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58. TOONE EC, IRBY R. Effect of cortisone in the long-term treatment of rheumatoid arthritis: observation of thirty-five patients over a three-year period. Am J Med. 1955 Jan; 18(1):41-50.
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59. MACKNIGHT JC, IRBY R, TOONE EC. Phenylbutazone in management of rheumatoid arthritis, rheumatoid spondylitis, and gouty arthritis. Geriatrics. 1954 Mar; 9(3):111-5.
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60. IRBY R. Congenital hemolytic anemia in Negro brothers; report of two cases. J Am Med Assoc. 1953 Sep 12; 153(2):103-4.
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61. IRBY R, HENNIGAR GR, KIRK J. Acute disseminated lupus erythematosus in the Negro male. Ann Intern Med. 1952 Dec; 37(6):1274-80.
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62. TUCKER HS, TALIAFERRO I, KIRKLAND RH, IRBY R. Addison's disease in the Negro. Am J Med Sci. 1952 May; 223(5):479-86.
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63. Tucker HS, Taliaferro I, Kirkland RH, Irby R. Addison's Disease in the Negro. Trans Am Clin Climatol Assoc. 1952; 63:8-20.
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Keyword
Last Name
Institution
    
 
 
 
Co-Authors  
Amin, Shantu
Loughran, Thomas
Nyland, Susan
Poritz, Lisa
Sharma, Arun
See all (14) people
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