Event Scheduled for Feb 3, 2012
Event: ME Spring 2012 Seminar Series and School of Engineering Distinguished Lecture, Prof. Mehmet Toner, Harvard
Location: UTEB 150
Time: 02:00 pm
Details of Event:
Viable tumor-derived circulating tumor cells (CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. The reliable isolation of CTCs using the microfluidic chip in metastatic cancer offers the possibility of monitoring patient response and changes in tumor genotypes during the course of treatment. However, the ability to isolate CTCs as a potential alternative to invasive biopsies as a source of tumor tissue for detection, characterization and monitoring of cancer patients have proven to be difficult due to the exceedingly low frequency of CTCs in circulation. We previously demonstrated the effectiveness of a microfluidic device, the CTC-Chip, in capturing rare CTCs using antibody-coated micro-posts under laminar flow conditions. More recently, we developed a second-generation chip based on high throughput microfluidic mixing approach, the herringbone-chip, or ‘HB-chip’, which provides an enhanced platform for CTC isolation. The HB-chip design applies passive mixing of blood cells through the generation of micro-vortices to dramatically increase the number of interactions between target CTCs and the antibody-coated chip surface. We applied the microfluidic platforms to blood samples obtained from metastatic lung, prostate, breast, colon, and pancreatic cancer patients. These studies with patient blood showed very high sensitivity and specificity of the microchip. We also tested the microchip in a cohort of patients with metastatic cancer undergoing systemic treatment and showed the temporal changes in CTC numbers correlated well with the clinical course of disease as measured by standard radiographic methods. To further show the utility of the CTC-chip, we isolated CTCs from patients with metastatic non-small-cell-lung cancer and identified the expected EGFR activating mutation in CTCs. We also detected the T790M mutation, which confers drug resistance, in CTCs collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. More recently, we applied microchip to isolate CTCs from blood specimens of patients with either metastatic or localized prostate cancer. Remarkably, the low shear design of the HB-chip revealed micro-clusters of CTCs in a subset of patient samples. Microscopic CTC aggregates may contribute to the hematogenous dissemination of cancer. Currently, the work is focused on dissemination of the technology to multiple clinical centers as well as the development of novel tools for high sensitivity detection of CTCs for early detection of cancer. This presentation will share our integrated strategy to simultaneously advance the engineering and microfluidics of CTC-Chip development, the biology of these rare cells, and the potential clinical applications of circulating tumor cells.
Dr. Toner received BS degree from Istanbul Technical University and MS degree from the Massachusetts Institute of Technology (MIT), both in Mechanical Engineering. Subsequently he completed his PhD degree in Medical Engineering at Harvard-MIT Division of Health Sciences and Technology in 1989. Since that time he has been on the faculty at Harvard Medical School. He was appointed as an assistant professor in 1990, promoted to associate professor in 1996, and to professor in 2002. Currently, he is the Helen Andrus Benedict Professor of Biomedical Engineering at the Massachusetts General Hospital, Harvard Medical School.
He is internationally regarded for his work in multiple areas including: (1) cryobiology, (2) tissue engineering, and (3) micro/nanotechnology and applications in cancer, burns and trauma, and HIV/AIDS. Dr. Toner has published >200 original papers in archival journals, including wide spectrum of high impact journals such as Nature, Science, New England Journal of Medicine, Science Translational Medicine, Nature Biotechnology, and PNAS. He has also delivered 350+ invited, keynote and plenary presentations.
Dr. Toner established the BioMicroElectroMechanical Systems Resource Center (BMRC) at the MGH and serves as its founding Director. This Center is primarily funded by NIH and aims to explore the applications of nano/micro-technologies in basic biology, systems biology, diagnostics and clinical medicine. In 1994, he was recognized by the “YC Fung Faculty Award” in Bioengineering. In 1995, he received the “Whitaker Foundation Special Opportunity Award.” In 1998, Dr Toner was selected to become a “Fellow of the American Institute of Medical and Biological Engineering.” In 2007, he became a “Fellow of the American Society of Mechanical Engineers.” In 2008, he was given “One-of-the hundred” award by the Massachusetts General Hospital cancer Center for his impact in cancer research. He was also recognized by the magazine “Popular Mechanics” as one of the top ten inventors in 2008. In 2010, he received the American Association of Cancer Research (AACR) Team Award.
Dr. Toner has served on many national and international panels and review boards. In 2010, he was selected to serve a three-year term on the NSF Directorate of Engineering, Board of Advisors. Dr. Toner serves on the scientific advisory board of Tissue Engineering Research Center at Tufts U/MIT/Columbia U, Resource for Synthesis and Bulk Characterization of Polymer Biomaterials at Rutgers U, Institute of Engineering and Medicine at UMinn, Center for Biomedical Engineering at UNC Charlotte, and Center for Biomedical Engineering at Brown U. Dr. Toner is also on the editorial board of various technical and scientific journals including Journal of Biomechanical Engineering, Cryo-Letters, Cryobiology (Associate Editor), Cell Preservation Technologies (Associate Editor), Nanomedicine, Integrated Biology, Nanolife, and Annual Review of Biomedical Engineering (Associate Editor and Co-Founder).
Among the > 70 graduate and postgraduate students trained by Toner today, >40 occupy major academic positions. Multiple of his alumni have received the NSF Career Award, NSF Presidential Young Investigator Award, NIH First Award, NIH Director’s Young Investigator Award, and multiple are now Fellows of AIMBE or ASME. A number of his former students secured endowed chairs or other prestigious awards such as Howard Hughes Medical Investigator (HHMI).
Target Audience: Open to All
Sponsored By: Mechanical Engineering
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