The Ian C. Summerhayes Cell and Molecular Biology (ICSCMB) Lab at Lahey Hospital & Medical Center performs translational research primarily focused on molecular oncology, and collaborates with high tech corporations pioneering methods of earlier detection of cancer. Additionally, the ICSCMB Lab is actively engaged in an NIH initiative known as TCGA or The Cancer Genome Atlas Project. TCGA is ‘a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies’.
The ICSCMB lab is focused on the discovery of new genes and cellular pathways implicated in cancer, enhancing understanding of how genetic variations affect the development and progression of cancer. A major focus of the research is to characterize the molecular changes in cancer patients’ tumors by analyzing DNA, RNA and proteins in the tumors and other bodily fluid. The molecular changes can be used as biomarkers for diagnosis, prognosis and prediction of response/resistance to treatment. The lab seeks to facilitate translational application of these findings, first to clinical research in oncology, then to patient care. Of course, the ultimate goal is for physicians to use these markers to select the best treatment with the fewest side effects for each patient.
One of the focuses of our lab is on the molecular basis of genitourinary cancers and improved treatments for patients with prostate, kidney and bladder cancer. Current laboratory research focuses on microRNA (miRNA), a small 22-27 nucleotide RNA species that serves as an mRNA regulator.
Two recent studies have investigated the use of miRNAs as biomarkers for urologic cancer staging. One study identified miRNAs in T1 TURBT specimens that correlate with upstaging at cystectomy. These miRNA have the potential to serve as biomarkers indicative of more aggressive disease. In the second study differential miRNA expression levels were investigated in TRUS biopsies with prostate cancer utilizing a tissue printing method. These samples demonstrated different miRNA expression levels between Gleason Sum (GS) groups (6 vs 7 vs >8). These distinct patterns suggest that certain miRNAs are important at specific stages of prostate cancer progression and holds promise to improve diagnosis, prognosis, and characterization of prostate cancer.
Research: Be a Part of It
Three ongoing studies in the ICSCMB Lab also focus on the utility of miRNAs as biomarkers of cancer staging:
- One study is investigating the potential of miRNAs to identify patients with GS6 prostate biopsies that are upstaged at prostatectomy.
- Another study is screening miRNAs to determine their potential in discriminating bladder cancer patients with occult metastasis.
- A third study is profiling kidney tumors in an effort to identify those individuals who are likely to progress to metastatic disease.
Biospecimen banking is storing excess human sample that has been removed during a medical procedure such as an operation, a biopsy, or a blood test. This extra material is not needed for your diagnosis or treatment. With your written consent, this material is placed in our biospecimen bank, where it is carefully preserved and protected. We use samples from these banks to study disease and find better ways to diagnose, prevent, and treat cancer in the future.
Rescue Lung/Rescue Life
Lung cancer kills more men and women in the United States than breast, colorectal, and prostate cancers combined with approximately 450 deaths from lung cancer every day. Starting in January 2012, Lahey Hospital & Medical Center began offering free Low Dose CT (LDCT) lung screening to individuals who meet the established high-risk criteria and to date, has evaluated more than 1300 patients.
Biomarkers have the potential to further stratify lung cancer risk in the subgroup of high risk patients, as well as confirming the presence of cancer in patients with suspicious findings. The biomarker-aided diagnosis then could prompt a more aggressive intervention including surgical resection. The current design of the lung screening is based on detecting morphological changes, which usually follow molecular traits with a delay of months to years. Adding biomarker-based testing to the work-up of patients with initial negative scan could increase the accuracy of diagnosis, influence the frequency of follow-up screening visits, improve outcomes, and ultimately reduce costs.
The ISCMB lab is establishing a unique high quality biological sample collection from patients in Lahey’s LDCT screening program. The acquired biosamples will be kept in biorepositories to support current studies on mRNA and miRNA as well as future correlative studies. Combining biomarkers and imaging may allow clinicians to eliminate patients from further diagnostic or therapeutic intervention who are at low risk of disease and to increase intervention for patients who are at increased risk.
Rieger-Christ KM, Mourtzinos A, Cain J, Silverman M, Libertino JA and Summerhayes IC. Identification of FGFR3 mutations in urine sediment DNA complements cytology in bladder tumor detection. Cancer 98:737-744, 2003.
Rieger-Christ KM, Lee P, Zagha R, Kosakowski M, Moinzadeh A, Stoffel J, Pezza JA, Ben-Ze’ev, Libertino JA and Summerhayes IC. Novel expression of N-cadherin elicits in vitro bladder cell invasion via the Akt signaling pathway. Oncogene 23:4745-4753, 2004.
Kim J, Zhang X, Rieger-Christ KM, Summerhayes IC, Wazer DE, Paulson E and Yee AS. Suppression of WNT signaling by the green tea compound EGCG in invasive breast cancer cells: Requirement of the transcriptional suppressor HBP1. J. Biol. Chem. 281:10865-10875, 2006.
Rieger-Christ KM, Hanley RS, Canes D, Boynton K, Shuber AP, Libertino JA and Summerhayes IC. DNA integrity assay (DIA): A plasma based screening tool for the detection of prostate cancer. Clin. Cancer Res. 12: 4569-4574, 2006.
Baumgart E, Cohen MS, Silva Neto B, Jacobs MA, Wotkowicz C, Rieger-Christ KM, Biolo A, Zeheb R, Loda M, Libertino JA and Summerhayes IC. Identification and prognostic significance of an epithelial-mesenchymal transition epression profile in human bladder tumors. Clin. Cancer Res. 13: 1685-1694, 2007.
Rieger-Christ KM, Hanley R, Lodowsky C, Bernier T, Yee AS, Libertino JA and Summerhayes IC. Down-regulation of N-cadherin expression and inactivation of Akt by EGCG accompanies suppression of migration in bladder carcinoma cells. J. Cell. Biochem. 102: 377-88, 2007.
Rieger-Christ KM, Paulson KE, McDevitt MA, Kuperwasser C, Kim J,Zhang X, Hu M, Berasi SP, Huang C-Y, Paganelli RH, Giri D, Kaufmann S, Dugan JM, Blum J, Netto G, Huang Z, Wazer DE, Summerhayes IC, Yee AS. Alterations of the HBP1 transcriptional repressor are associated with invasive breast cancer. Cancer Res. 67: 6136-45, 2007.
Rieger-Christ KM, Neeley LA, Silva Neto B, Eroshkin A, Garver J, Patel S, Phung NA, McLaughlin S, Libertino JA, Whitney D and Summerhayes IC. A microRNA expression signature characterizing the invasive phenotype in bladder tumors. Urol Oncol. 28: 39-48, 2010.
Kozinn SI, Harty NJ, DeLong JM, Deliyiannis C, Logvinenko T, Summerhayes IC, Holway AH, Libertino JA, Rieger-Christ KM. MicroRNA profile predicts gemcitabine resistance in bladder carcinoma cell lines. (In press, Genes and Cancer)