MAIN CONFERENCE
MONDAY, MARCH 23
1:00-2:00 Conference Registration
2:00-2:10 Welcoming Remarks from Conference Director
Julia Boguslavsky, Executive Director, Conferences, Cambridge Healthtech Institute
Special Focus: microRNA in Cancer
2:10-2:15 Chairperson’s Opening Remarks
Frank Slack, Ph.D., Associate Professor, Department of Molecular, Cellular and Developmental Biology, Yale University
2:15-2:40 microRNAs in Cancer
Frank Slack, Ph.D., Associate Professor, Department of Molecular, Cellular and Developmental Biology, Yale University
MicroRNAs are small non-coding RNAs that regulate gene expression to control important aspects of development and metabolism such as cell differentiation, apoptosis and lifespan. let-7 encodes a microRNA implicated in human cancer. Specifically, human let-7 is poorly expressed or deleted in lung cancer, and over-expression of let-7 in lung cancer cells inhibits their growth, demonstrating a role for let-7 as a tumor suppressor in lung tissue. let-7 is expressed in the developing mammalian lung and regulates the expression of important oncogenes implicated in lung cancer, suggesting a mechanism for let-7’s involvement in cancer. We are focused on the role of let-7 and other oncomirs in regulating proto-oncogene expression during development and cancer, and on using miRNAs to suppress tumorigenesis.
2:40-3:05 Diagnostic and Therapeutic microRNA Strategies in Ovarian Cancer
Lin Zhang, M.D., Research Assistant Professor, Center for Research on the Early Detection & Cure of Ovarian Cancer, Center for Research on Reproduction and Women’s Health, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine
miRNAs are ~22 nucleotide non-coding RNAs, which negatively regulate gene expression in a sequence-specific manner. Increasing evidence indicates that miRNAs are key regulators of various fundamental biological processes. We have reported that miRNAs exhibit genomic alterations at high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. Indeed, our recent studies indicate that a miRNA-based method is a novel strategy with strong potential application to human ovarian cancer in early detection, diagnosis and treatment.
3:05-3:30 microRNA Signature in Waldenstrom Macroglobulinemia
Aldo Roccaro, M.D., Ph.D., Instructor in Medicine, Harvard Medical School
We analyzed microRNA expression in CD19+ cells isolated from bone marrow of patients with Waldenstrom Macroglobulinemia (WM) compared to CD19+ cells isolated from bone marrow and peripheral blood of healthy donors, and identified a specific signature in WM patients characterized by overexpression of microRNA-363*, -206, -494, -155, -184, and -542-3p; and downregulation of microRNA-9*. Further confirmation of these miRNAs was performed using real-time PCR analysis on the same samples. The expression of these miRNA correlated with poor prognostic features in WM. We then focused on the functional role of microRNA-155, and demonstrated that it regulates proliferation and growth of WM cells in vitro and in vivo by inhibiting signaling cascades including MAPK/ERK, PI3/AKT and NF-kB pathways. Moreover, we further explored whether commonly used therapeutic agents alter levels of the 7 major microRNAs identified, and demonstrated that rituximab, perifosine, and bortezomib treatment in WM cell line induced downmodulation of patient-overexpressed microRNAs (all but microRNA-206) and upregulation of patient-downexpressed microRNA (microRNA-9*). These data indicate that miRNAs play a pivotal role in the biology of WM; represent important prognostic markers; and provide the basis for the development of new miRNA-based targeted therapies in this disease.
3:30-3:55 Networking Refreshment Break
3:55-4:20 MicroRNAs and Brain Tumors
Sean Lawler, Ph.D., Assistant Professor, Neurological Surgery, Ohio State University
My group has recently identified several microRNA alterations in human glioblastoma patient samples. We have shown that these alterations can affect hallmark processes in glioblastoma such as cell proliferation and invasion. We have also identified that miR-128 regulates the self renewal of cancer stem cell through its target Bmi-1. These data are revealing novel therapeutic approaches for this difficult disease.
4:20-4:35 Sponsored Presentation (Opportunity available)
Contact Jon Stroup, Manager, Business Development, at jstroup@healthtech.com or 781-972-5483.
4:35-5:00 The Role of the let-7 microRNA Family During Cancer Progression
Aurora Esquela-Kerscher, Ph.D., Assistant Professor, Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School
MicroRNAs regulate important developmental events in animals and are closely correlated with human cancers. The let-7 miRNA family is postulated to function as tumor suppressor genes in a variety of human tissues, particularly in the lung, by regulating the oncogenes RAS, MYC, and HMGA2 as well as several cell cycle progression genes. We are investigating the role of let-7 during development and cancer progression in both nematode and mammalian systems as well as the use of miRNAs to suppress tumorigenesis.
5:00-6:00 Opening Reception with Exhibit and Poster Viewing
Sponsorship opportunity available. Contact Jon Stroup, Manager, Business Development, at jstroup@healthtech.com or 781-972-5483.