Melinda E. Sanders, M.D.

Faculty Appointments
Professor of Pathology, Microbiology and Immunology
M.D., Thomas Jefferson University, Jefferson Medical College, Philadelphia, PennsylvaniaB.S., Zoology, Duke University, Durham, North Carolina
Office Address
Vanderbilt University Medical Center
MCN C-3322
1161 21st Avenue South
Nashville, TN 37232-2561
Research Description
My research endeavors include studies of proliferative breast disease and breast cancer. I am engaged in both discovery projects and investigation of specific genetic alterations. My work is principally funded by a Vanderbilt Physician Scientist Development Award and the Breast Cancer S.P.O.R.E. through which I have received a Career Development Award. My main effort is characterization of the molecular changes accompanying the pre-invasive to invasive breast cancer transition. This is an important focus for breast cancer research because extensive epidemiologic data have shown the most critical event in mammary neoplasia to be the transition from ductal carcinoma in situ (DCIS) to invasive mammary carcinoma (IMC). Approximately one third of women diagnosed with IMC in 2003 will subsequently develop metastatic disease and die as a result. In contrast, DCIS is a non-invasive process which by definition has no metastatic capacity with survival rates comparable to those of women in the general population. Differences in gene and protein expression should be responsible for these strikingly different clinical phenotypes and are under investigation using cDNA microarrays and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The goal of these projects is to determine the expression differences which are predictive of biologic behavior both between and within these groups. These are discovery projects which will result in identification of genes and/or proteins associated with breast cancer invasion. The causal and mechanistic association of these genes and/or proteins with breast cancer invasiveness will be subsequently studied in appropriate cell and mouse models. Furthermore, epidemiologic validation linking invasion-associated genes and proteins with clinical outcome can be explored in databases with appropriate clinical follow-up such as the Nashville Breast Cohort. Additional projects include 1) The relationship of the transforming growth factor-¿Ò1 T29C polymorphism to breast cancer risk, 2) Interdependence of radial scar and proliferative disease with respect to invasive breast cancer risk in benign breast biopsies, and 3) p27 haploinsufficiency in invasive breast cancer.
Research Keywords
Breast Cancer and Proliferative Breast Disease
Oppenheimer SR, Mi D, Sanders ME, Caprioli RM. Molecular analysis of tumor margins by MALDI mass spectrometry in renal carcinoma. J. Proteome Res. 2010 May 5/7/2010; 9(5): 2182-90. PMID: 20141219, PMCID: PMC2866033, DOI: 10.1021/pr900936z, ISSN: 1535-3907.

Bauer JA, Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, De Matos Granja-Ingram N, Olivares MG, Kelley MC, Mayer IA, Meszoely IM, Means-Powell JA, Johnson KN, Tsai CJ, Ayers GD, Sanders ME, Schneider RJ, Formenti SC, Caprioli RM, Pietenpol JA. Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin. Cancer Res [print-electronic]. 2010 Jan 1/15/2010; 16(2): 681-90. PMID: 20068102, PMCID: PMC2892225, PII: 1078-0432.CCR-09-1091, DOI: 10.1158/1078-0432.CCR-09-1091, ISSN: 1078-0432.

Dupont WD, Breyer JP, Bradley KM, Schuyler PA, Plummer WD, Sanders ME, Page DL, Smith JR. Protein phosphatase 2A subunit gene haplotypes and proliferative breast disease modify breast cancer risk. Cancer. 2010 Jan 1/1/2010; 116(1): 8-19. PMID: 19890961, PMCID: PMC2807897, DOI: 10.1002/cncr.24702, ISSN: 0008-543X.

Breyer JP, Sanders ME, Airey DC, Cai Q, Yaspan BL, Schuyler PA, Dai Q, Boulos F, Olivares MG, Bradley KM, Gao YT, Page DL, Dupont WD, Zheng W, Smith JR. Heritable variation of ERBB2 and breast cancer risk. Cancer Epidemiol. Biomarkers Prev [print-electronic]. 2009 Apr; 18(4): 1252-8. PMID: 19336545, PMCID: PMC2730036, PII: 1055-9965.EPI-08-1202, DOI: 10.1158/1055-9965.EPI-08-1202, ISSN: 1055-9965.

Boulos FI, Dupont WD, Simpson JF, Schuyler PA, Sanders ME, Freudenthal ME, Page DL. Histologic associations and long-term cancer risk in columnar cell lesions of the breast: a retrospective cohort and a nested case-control study. Cancer. 2008 Nov 11/1/2008; 113(9): 2415-21. PMID: 18816618, PMCID: PMC3121952, DOI: 10.1002/cncr.23873, ISSN: 0008-543X.

Sanders ME, Dias EC, Xu BJ, Mobley JA, Billheimer D, Roder H, Grigorieva J, Dowsett M, Arteaga CL, Caprioli RM. Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. J. Proteome Res [print-electronic]. 2008 Apr; 7(4): 1500-7. PMID: 18386930, PMCID: PMC2738605, DOI: 10.1021/pr7008109, ISSN: 1535-3893.

Guix M, Granja Nde M, Meszoely I, Adkins TB, Wieman BM, Frierson KE, Sanchez V, Sanders ME, Grau AM, Mayer IA, Pestano G, Shyr Y, Muthuswamy S, Calvo B, Krontiras H, Krop IE, Kelley MC, Arteaga CL. Short preoperative treatment with erlotinib inhibits tumor cell proliferation in hormone receptor-positive breast cancers. J. Clin. Oncol [print-electronic]. 2008 Feb 2/20/2008; 26(6): 897-906. PMID: 18180460, PII: JCO.2007.13.5939, DOI: 10.1200/JCO.2007.13.5939, ISSN: 1527-7755.

Cornett DS, Mobley JA, Dias EC, Andersson M, Arteaga CL, Sanders ME, Caprioli RM. A novel histology-directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer. Mol. Cell Proteomics [print-electronic]. 2006 Oct; 5(10): 1975-83. PMID: 16849436, PII: M600119-MCP200, DOI: 10.1074/mcp.M600119-MCP200, ISSN: 1535-9476.

McLaren BK, Schuyler PA, Sanders ME, Jensen RA, Simpson JF, Dupont WD, Page DL. Excellent survival, cancer type, and Nottingham grade after atypical lobular hyperplasia on initial breast biopsy. Cancer. 2006 Sep 9/15/2006; 107(6): 1227-33. PMID: 16894523, DOI: 10.1002/cncr.22113, ISSN: 0008-543X.

Sanders ME, Page DL, Simpson JF, Schuyler PA, Dale Plummer W, Dupont WD. Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies. Cancer. 2006 Apr 4/1/2006; 106(7): 1453-61. PMID: 16502407, DOI: 10.1002/cncr.21730, ISSN: 0008-543X.

Wu FY, Wang SE, Sanders ME, Shin I, Rojo F, Baselga J, Arteaga CL. Reduction of cytosolic p27(Kip1) inhibits cancer cell motility, survival, and tumorigenicity. Cancer Res. 2006 Feb 2/15/2006; 66(4): 2162-72. PMID: 16489017, PII: 66/4/2162, DOI: 10.1158/0008-5472.CAN-05-3304, ISSN: 0008-5472.

Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer. 2005 Jun 6/15/2005; 103(12): 2481-4. PMID: 15884091, DOI: 10.1002/cncr.21069, ISSN: 0008-543X.

Chaurand P, Sanders ME, Jensen RA, Caprioli RM. Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. Am. J. Pathol. 2004 Oct; 165(4): 1057-68. PMID: 15466373, PMCID: PMC3118833, PII: S0002-9440(10)63367-6, DOI: 10.1016/S0002-9440(10)63367-6, ISSN: 0002-9440.

Muraoka RS, Koh Y, Roebuck LR, Sanders ME, Brantley-Sieders D, Gorska AE, Moses HL, Arteaga CL. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Mol. Cell. Biol. 2003 Dec; 23(23): 8691-703. PMID: 14612410, PMCID: PMC262670, ISSN: 0270-7306.

Reid G, Sanders ME, Gaskins HR, Gibson GR, Mercenier A, Rastall R, Roberfroid M, Rowland I, Cherbut C, Klaenhammer TR. New scientific paradigms for probiotics and prebiotics. J. Clin. Gastroenterol. 2003 Aug; 37(2): 105-18. PMID: 12869879, ISSN: 0192-0790.

Xu BJ, Caprioli RM, Sanders ME, Jensen RA. Direct analysis of laser capture microdissected cells by MALDI mass spectrometry. J. Am. Soc. Mass Spectrom. 2002 Nov; 13(11): 1292-7. PMID: 12443019, DOI: 10.1016/S1044-0305(02)00644-X, ISSN: 1044-0305.

Sanders ME, Mick R, Tomaszewski JE, Barr FG. Unique patterns of allelic imbalance distinguish type 1 from type 2 sporadic papillary renal cell carcinoma. Am. J. Pathol. 2002 Sep; 161(3): 997-1005. PMID: 12213728, PMCID: PMC1867241, PII: S0002-9440(10)64260-5, DOI: 10.1016/S0002-9440(10)64260-5, ISSN: 0002-9440.

Yeung PS, Sanders ME, Kitts CL, Cano R, Tong PS. Species-specific identification of commercial probiotic strains. J. Dairy Sci. 2002 May; 85(5): 1039-51. PMID: 12086037, PII: S0022-0302(02)74164-7, DOI: 10.3168/jds.S0022-0302(02)74164-7, ISSN: 0022-0302.

Seibold JR, Korn JH, Simms R, Clements PJ, Moreland LW, Mayes MD, Furst DE, Rothfield N, Steen V, Weisman M, Collier D, Wigley FM, Merkel PA, Csuka ME, Hsu V, Rocco S, Erikson M, Hannigan J, Harkonen WS, Sanders ME. Recombinant human relaxin in the treatment of scleroderma. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 2000 Jun 6/6/2000; 132(11): 871-9. PMID: 10836913, PII: 200006060-00004, ISSN: 0003-4819.

Fogt F, Urbanski SJ, Sanders ME, Furth EE, Zimmerman RL, Deren JJ, Noffsinger AE, Vortmeyer AO, Hartmann CJ, Odze RL, Brown CA. Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis. Hum. Pathol. 2000 Mar; 31(3): 288-91. PMID: 10746669, ISSN: 0046-8177.

Sanders ME, van de Rijn M, Barr FG. Detection of a variant SYT-SSX1 fusion in a case of predominantly epithelioid synovial sarcoma. Mol. Diagn. 1999 Mar; 4(1): 65-70. PMID: 10229776, PII: S1084-8592(99)80051-4, DOI: 10.154/MODI00400065, ISSN: 1084-8592.

Chin JE, Winterrowd GE, Krzesicki RF, Sanders ME. Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular adhesion molecule 1 and HLA class I and class II antigens in rheumatoid synovial fibroblasts. Arthritis Rheum. 1990 Dec; 33(12): 1776-86. PMID: 1701992, ISSN: 0004-3591.

Kursunoglu-Brahme S, Riccio T, Weisman MH, Resnick D, Zvaifler N, Sanders ME, Fix C. Rheumatoid knee: role of gadopentetate-enhanced MR imaging. Radiology. 1990 Sep; 176(3): 831-5. PMID: 2389044, DOI: 10.1148/radiology.176.3.2389044, ISSN: 0033-8419.

Basinger MA, Jones MM, Craft WD, Walker EM, Sanders MM. Chelating-agent suppression of cadmium-induced hepatotoxicity. J Toxicol Environ Health. 1987; 22(3): 261-71. PMID: 2890768, DOI: 10.1080/15287398709531070, ISSN: 0098-4108.