Shanna Alexandria Arnold, Ph.D.

Research Assistant Professor

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Faculty Appointments
Research Assistant Professor of Pathology, Microbiology and Immunology
M.S.C.I., Clinical Investigation, Vanderbilt University, Nashville, TennesseePh.D., Integrative Biology, University of Texas Southwestern Medical Center, Dallas, TexasB.S., Biology, Texas Christian University, Fort Worth, Texas
Office Address
1161 21st Ave S.
MCN C-2103
Nashville, TN 37232
Research Description
It is estimated that there will be 140,430 new diagnoses of urogenital cancers and 30,000 associated deaths in 2013. Metastatic progression is the primary cause of cancer-related death. Managing care for cancer patients with progressive disease is an arduous challenge and poses an increasing financial burden on our medical institutions. Therefore, is imperative that we elucidate the molecular mechanisms that drive metastasis and identify clinical biomarkers that can specifically recognize invasive disease and rapidly assess therapeutic response. Our objective is to discover and validate fluid-based biomarkers for disease surveillance, monitoring treatment response, and predicting recurrence. Furthermore, we aim to determine the mechanisms underlying these biomarkers that drive tumor cell survival and migration.

We have identified Activated Leukocyte Cell Adhesion Molecule (ALCAM) as an important regulator of tumor cell motility and metastasis in both pre-clinical and mechanistic studies. We have demonstrated that ALCAM is a critical contributor to tumor cell metastasis. By analyzing ALCAM in the serum of tumor-bearing animals, we demonstrated that shedding of the extracellular domain of ALCAM corresponds to disease progression and tumor burden. Furthermore, we found significantly elevated ALCAM levels in both the urine and serum of patients with renal (RCC) and bladder (BCa) cancer. Based on our preliminary studies, we hypothesize that the proteolytic shedding of ALCAM contributes to disease progression and that shed ALCAM is a biomarker of disease progression, as well as treatment response in urogenital cancers. The value of shed ALCAM as a biomarker is two-fold: 1) It is a mechanistic link to tumor cell migration and, subsequently, able to report on invasive disease rather than merely the presence of cancer, and 2) The non-invasive detection of ALCAM in urine and serum offers longitudinal assessment of treatment response and disease progression. In addition, understanding how proteolytic processing of ALCAM contributes mechanistically to disease progression will reveal therapeutic approaches that can intervene in the malignant dissemination of cancer.

Our research plan has three aspects that include validating ALCAM as a biomarker in urogenital cancers, determining the function of various ALCAM domains in tumor cell survival and metastasis, and discovering new biomarkers similar to ALCAM in function and utility.

The clinical impact of such biomarkers would be multifaceted by reducing healthcare costs, reducing toxicities associated with ineffective drugs, and improving the implementation of drug trials. In summary, successful implementation of active monitoring for recurrence and rapid identification of treatment response is synonymous with reducing morbidity, mortality, and the associated cost of health care.
Research Keywords
Translational Research of Biomarkers in Urogenital Cancers
David SN, Arnold Egloff SA, Goyal R, Clark PE, Phillips S, Gellert LL, Hameed O, Giannico GA. MAGI2 is an independent predictor of biochemical recurrence in prostate cancer. Prostate [print-electronic]. 2018 Jun; 78(8): 616-22. PMID: 29542165, DOI: 10.1002/pros.23506, ISSN: 1097-0045.

Hebron KE, Li EY, Arnold Egloff SA, von Lersner AK, Taylor C, Houkes J, Flaherty DK, Eskaros A, Stricker TP, Zijlstra A. Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion through differential proteolysis. Sci Rep. 2018 Feb 2/16/2018; 8(1): 3208. PMID: 29453336, PMCID: PMC5816644, PII: 10.1038/s41598-018-21467-x, DOI: 10.1038/s41598-018-21467-x, ISSN: 2045-2322.

Eskaros AR, Egloff SA, Boyd KL, Richardson JE, Hyndman ME, Zijlstra A. Larger core size has superior technical and analytical accuracy in bladder tissue microarray. Lab. Invest [print-electronic]. 2017 Mar; 97(3): 335-42. PMID: 28112755, PII: labinvest2016151, DOI: 10.1038/labinvest.2016.151, ISSN: 1530-0307.

Cate F, Kapp M, Arnold SA, Gellert LL, Hameed O, Clark PE, Wile G, Coogan A, Giannico GA. Core Needle Biopsy and Fine Needle Aspiration Alone or in Combination: Diagnostic Accuracy and Impact on Management of Renal Masses. J. Urol [print-electronic]. 2017 Jan 1/13/2017; PMID: 28093293, PII: S0022-5347(17)30064-2, DOI: 10.1016/j.juro.2017.01.038, ISSN: 1527-3792.

Giannico GA, Arnold SA, Gellert LL, Hameed O. New and Emerging Diagnostic and Prognostic Immunohistochemical Biomarkers in Prostate Pathology. Adv Anat Pathol. 2017 Jan; 24(1): 35-44. PMID: 27941540, PII: 00125480-201701000-00004, DOI: 10.1097/PAP.0000000000000136, ISSN: 1533-4031.

Loomans HA, Arnold SA, Hebron K, Taylor CJ, Zijlstra A, Andl CD. Loss of ACVRIB leads to increased squamous cell carcinoma aggressiveness through alterations in cell-cell and cell-matrix adhesion proteins. Am J Cancer Res. 2017; 7(12): 2422-37. PMID: 29312797, PMCID: PMC5752684, ISSN: 2156-6976.

Arnold Egloff SA, Du L, Loomans HA, Starchenko A, Su PF, Ketova T, Knoll PB, Wang J, Haddad AQ, Fadare O, Cates JM, Lotan Y, Shyr Y, Clark PE, Zijlstra A. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer. Oncotarget [print-electronic]. 2016 Nov 11/24/2016; PMID: 27894096, PII: 13546, DOI: 10.18632/oncotarget.13546, ISSN: 1949-2553.

Loomans HA, Arnold SA, Quast LL, Andl CD. Esophageal squamous cell carcinoma invasion is inhibited by Activin A in ACVRIB-positive cells. BMC Cancer. 2016 Nov 11/9/2016; 16(1): 873. PMID: 27829391, PMCID: PMC5101642, PII: 10.1186/s12885-016-2920-y, DOI: 10.1186/s12885-016-2920-y, ISSN: 1471-2407.

Goldstein J, Borowsky AD, Goyal R, Roland JT, Arnold SA, Gellert LL, Clark PE, Hameed O, Giannico GA. MAGI-2 in prostate cancer: an immunohistochemical study. Hum. Pathol [print-electronic]. 2016 Jun; 52: 83-91. PMID: 26980016, PII: S0046-8177(16)00035-6, DOI: 10.1016/j.humpath.2016.01.003, ISSN: 1532-8392.

Arnold SA, Loomans HA, Ketova T, Andl CD, Clark PE, Zijlstra A. Urinary oncofetal ED-A fibronectin correlates with poor prognosis in patients with bladder cancer. Clin. Exp. Metastasis [print-electronic]. 2016 Jan; 33(1): 29-44. PMID: 26456754, PMCID: PMC4742427, PII: 10.1007/s10585-015-9754-x, DOI: 10.1007/s10585-015-9754-x, ISSN: 1573-7276.

Giannico GA, Arnold S, Langone A, Schaefer H, Helderman JH, Shaffer D, Fogo AB. Non-immunoglobulin A mesangial immune complex glomerulonephritis in kidney transplants. Hum. Pathol [print-electronic]. 2015 Oct; 46(10): 1521-8. PMID: 26245687, PII: S0046-8177(15)00217-8, DOI: 10.1016/j.humpath.2015.06.012, ISSN: 1532-8392.

Oakley FD, Woods M, Arnold S, Young PP. Transfusion reactions in pediatric compared with adult patients: a look at rate, reaction type, and associated products. Transfusion [print-electronic]. 2015 Mar; 55(3): 563-70. PMID: 25145580, DOI: 10.1111/trf.12827, ISSN: 1537-2995.

Hansen AG, Arnold SA, Jiang M, Palmer TD, Ketova T, Merkel A, Pickup M, Samaras S, Shyr Y, Moses HL, Hayward SW, Sterling JA, Zijlstra A. ALCAM/CD166 is a TGF-ß-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res [print-electronic]. 2014 Mar 3/1/2014; 74(5): 1404-15. PMID: 24385212, PMCID: PMC4149913, PII: 0008-5472.CAN-13-1296, DOI: 10.1158/0008-5472.CAN-13-1296, ISSN: 1538-7445.

Palmer TD, Martínez CH, Vasquez C, Hebron KE, Jones-Paris C, Arnold SA, Chan SM, Chalasani V, Gomez-Lemus JA, Williams AK, Chin JL, Giannico GA, Ketova T, Lewis JD, Zijlstra A. Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. Cancer Res [print-electronic]. 2014 Jan 1/1/2014; 74(1): 173-87. PMID: 24220242, PMCID: PMC3947299, PII: 0008-5472.CAN-13-0275, DOI: 10.1158/0008-5472.CAN-13-0275, ISSN: 1538-7445.

Hansen AG, Freeman TJ, Arnold SA, Starchenko A, Jones-Paris CR, Gilger MA, Washington MK, Fan KH, Shyr Y, Beauchamp RD, Zijlstra A. Elevated ALCAM shedding in colorectal cancer correlates with poor patient outcome. Cancer Res [print-electronic]. 2013 May 5/15/2013; 73(10): 2955-64. PMID: 23539446, PMCID: PMC3660148, PII: 0008-5472.CAN-12-2052, DOI: 10.1158/0008-5472.CAN-12-2052, ISSN: 1538-7445.

Arnold SA, Rivera LB, Carbon JG, Toombs JE, Chang CL, Bradshaw AD, Brekken RA. Losartan slows pancreatic tumor progression and extends survival of SPARC-null mice by abrogating aberrant TGFß activation. PLoS ONE [print-electronic]. 2012; 7(2): e31384. PMID: 22348081, PMCID: PMC3279359, PII: PONE-D-11-19108, DOI: 10.1371/journal.pone.0031384, ISSN: 1932-6203.

Arnold SA, Rivera LB, Miller AF, Carbon JG, Dineen SP, Xie Y, Castrillon DH, Sage EH, Puolakkainen P, Bradshaw AD, Brekken RA. Lack of host SPARC enhances vascular function and tumor spread in an orthotopic murine model of pancreatic carcinoma. Dis Model Mech [print-electronic]. 2010 Jan; 3(1-2): 57-72. PMID: 20007485, PMCID: PMC2806901, PII: dmm.003228, DOI: 10.1242/dmm.003228, ISSN: 1754-8411.

Arnold SA, Brekken RA. SPARC: a matricellular regulator of tumorigenesis. J Cell Commun Signal [print-electronic]. 2009 Dec; 3(3-4): 255-73. PMID: 19809893, PMCID: PMC2778590, DOI: 10.1007/s12079-009-0072-4, ISSN: 1873-961X.

Bull Phelps SL, Carbon J, Miller A, Castro-Rivera E, Arnold S, Brekken RA, Lea JS. Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity. Am. J. Obstet. Gynecol [print-electronic]. 2009 Feb; 200(2): 180.e1-7. PMID: 18992864, PMCID: PMC3709016, PII: S0002-9378(08)00983-6, DOI: 10.1016/j.ajog.2008.08.047, ISSN: 1097-6868.

Arnold S, Mira E, Muneer S, Korpanty G, Beck AW, Holloway SE, Mañes S, Brekken RA. Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. Exp. Biol. Med. (Maywood) [print-electronic]. 2008 Jul; 233(7): 860-73. PMID: 18445772, PMCID: PMC2459223, PII: 0801-RM-12, DOI: 10.3181/0801-RM-12, ISSN: 1535-3702.