Sunday, February 07, 2010
2:00pm - 5:40pm

Lecturers: Dr. Gabriel Lopez-Berestein, David D McPherson, Renata Pasqualini, Anil K. Sood

Course Description and Outline
Module 1 - Presented by David D McPherson:
Taking the Correct Concept and Translating Engineering into Biology: Biomedical Engineering: Targeted Molecular Imaging and Drug and Gene Delivery

Many challenges in biomedical engineering lay not with respect to the engineering input but more in identifying the correct biologic concepts that need engineering expertise to develop these concepts. If these concepts are poorly identified and characterized, then challenges will exist in bringing the concept into a clinical medicine.

This review will primarily utilize cardiovascular and cancer questions in which biomedical engineering expertise is required and areas where biomedical expertise has fallen short in addressing biologic concepts. Targeted Molecular Imaging; and Drug and Gene Delivery will be used as examples where biomedical engineering expertise is intimately required for the development of strategies to help us better understand and treat disease pathology.

References:

1. Laing ST. McPherson DD. Cardiovascular Therapeutic Uses of Targeted Ultrasound Contrast. Cardiovasc Res 2009; 4:626-635.
2. Porter T. The utilization of Ultrasound and microbubbles for therapy in acute coronary syndromes. Cardiovasc Res 2009 4:636-642
3. Linder J. Contrast ultrasound molecular imaging: harnessing the power of bubbles. Cardiovasc Res 2009 4:615-616

Module 2 - Presented by Renata Pasqualini:
Ligand-directed therapy and molecular imaging based on in vivo phage display technology: translational updates in nanomedicine applications.

Our central working hypothesis is that differential protein expression in the human vascular endothelium associated with normal or diseased tissues offers the potential for developing novel diagnostic, imaging, and therapeutic strategies. In essence, our research program uses combinatorial library selection (peptide- and antibody-based) to discover, validate, and exploit the vascular biochemical diversity of endothelial cell surfaces. Such targeting technologies have already led to the development of ligand-directed agents for potential application in the treatment of cancer patients. Translational milestones, such as a first-in-man clinical trial based on this technology, have recently been met, based on an M.D. Anderson Cancer Center sponsored IND. Other drugs and imaging agents are in pre-IND stage and several others are in pre-clinical laboratory phase. Long-term, the broader vision of our research is a large-scale mapping of receptors in human vasculature towards a new ligand-directed pharmacology. As we enter an age of engineering molecular assemblies, the combination of nanotechnology, phage display, and biophotonics offers remarkable opportunities to improve the diagnosis and treatment of many diseases. It is not trivial to design and implement an entity with nanodimensions that can reproducibly and effectively integrate different functions such as signal reporting, tissue targeting, drug delivery, as well as carrying therapeutic functions. The concept being developed as part of a collaborative effort with several laboratories combines phage display technology and gold nanoparticles (Au) in a "bottom-up" molecular direct assembly of Au and phage into the Au-phage "scaffold" structures (Au-phage scaffold). Such nanoassemblies show unique optical properties, including the capability of converting near infrared (NIR) radiation into heat, providing signal enhancement for fluorescent imaging and surface enhanced Raman scattering (SERS) detection. The combination of NIR optical properties and the programmable targeting capabilities of phage allow Au-phage scaffolds to carry targeted therapeutic and detection functions.

Module 3 - Presented by A.K. Sood:
Interfering with Tumor Vasculature

The progressive growth of ovarian cancer and associated metastases is dependent on an adequate blood supply (angiogenesis). Targeting angiogenesis is a particularly attractive strategy because of the presumed genetic stability of endothelial cells. This is best illustrated by recent successes of anti-angiogenic therapy (e.g., bevacizumab) in patients with solid tumors. However, despite initial responses, most patients eventually develop tumor progression resulting in their demise. Therefore, new anti-angiogenesis therapeutic strategies are needed. We are utilizing novel approaches for identifying and targeting the tumor vasculature. Genomic profiling studies of endothelial cells from cancer vasculature compared to normal endothelial cells have identified a number of novel targets (e.g., EZH2, Jag1). Since many of these are difficult to target with conventional approaches, we are utilizing RNAi strategies coupled with novel biocompatible nanoparticles. Among these, chitosan nanoparticles are highly attractive for targeting the angiogenic tumor vasculature. We have carried out a series of studies using both passive and active targeting for silencing critical genes for tumor angiogenesis. These and other approaches will be discussed in detail in this lecture.

Module 4- Presented by G. Lopez-Berestein:
In preparation

Lecturers

		Gabriel Lopez-Berestein Professor of Medicine and Cancer Biology Department of Experimental Therapeutics Executive Director of the Pharmaceutical Development Center University of Texas M. D. Anderson Cancer Center (MDACC) Dr. Gabriel Lopez-Berestein currently serves as a Professor of Medicine and Cancer Biology in the Department of Experimental Therapeutics and as the Executive Director of the Pharmaceutical Development Center at the University of Texas M. D. Anderson Cancer Center (MDACC). Dr. Lopez-Berestein has been working at M.D. Anderson Cancer Center since 1979 and has more than 30 years of experience in cancer research. He has published more than 200 research articles, reviews, and book chapters and has edited books in the area of cancer research. Dr. Lopez-Berestein's two major areas of interest are nanoparticulate carriers for the delivery of nucleotides and small molecules in the treatment of cancer, cell differentiation and apoptosis signaling in acute promyelocytic leukemia (APL). As part of his interest in apoptosis and differentiation in cancer, he characterized the role of posttranscriptional events in the ATRA induced differentiation in leukemia cells. These findings led to the identification of several proteins involved in key regulatory pathways of cell growth both in solid and hematologic malignancies. He has demonstrated that retinoic acid (RA) induces post-transcriptional suppressive pathways during differentiation. These processes involve eukaryotic initiation, elongation factors, and protein phosphatases 2A; these were found to function in pre-mRNA processing, splicing and export. More recently, he has shown that one of the apoptotic proteins, DAP5/86, was involved in the repression of translation thus playing a potential role in differentiation and resistance in APL cells. These findings provide potential novel post-transcriptional regulatory mechanisms in APL and may serve as a model for differentiation induction in other cell types. Dr. Lopez-Berestein's laboratory exploited the use of lipid based carriers for the delivery of antifungal and anticancer agents. Dr. Lopez-Berestein's present efforts are concentrated on the development of nanoliposomes and nanoparticles for the delivery of siRNA to target major signaling pathways in cancer. Several of these targets were identified to play a prominent role in cell growth in our laboratory. Dr. Lopez-Berestein brought from concept to clinic, seven different antimicrobial and antitumor agents, of which one, Abelcet, reached the market and others are in different stages of clinical development.
		D.D McPherson Head Division of Cardiology The University of Texas Health Science Center at Houston Dr. McPherson was trained at the University of Alberta, Dalhousie University and the University of Iowa. In 1989, he was recruited to Northwestern University to develop an ultrasound based imaging group. Recruited to The University of Texas Health Science Center at Houston to head the Division of Cardiology 2006. Dr. McPherson is the recipient of many distinctions, awards and grants for the development and use of new and innovative ultrasound tools and devices for the evaluation and treatment of atherosclerosis in coronary and peripheral vascular beds. These include the National Institutes of Health and American Heart Association awards. He is a reviewer for many journals including Circulation, Circulation Research, and the American Journal of Physiology; is on the editorial board of the American Journal of Physiology; is a standing grant reviewer/grant review co-chairman for the National Institutes of Health and the American Heart Association; and is on councils and committees for the American Society of Echocardiography, American Federation for Clinical Research and American Heart Association. He is a supervisor for biomedical engineering doctoral students, cardiology fellows, residents, and medical students training in advanced echocardiographic research. Prior to coming to Texas, he was responsible for a large advanced echocardiography training course for the Midwest Clinical interests include, the evaluation of valvular heart disease, adult congenital cardiology, and clinical echocardiography including transesophageal echocardiography (TEE). Current research projects include; the development of new acoustic agents for ultrasound tissue enhancement and targeted drug and gene delivery; the development of new ultrasound techniques to guide angioplasty and stent placement; and new three dimensional techniques for cardiac and vascular reconstruction. Dr. McPherson is the author of 105 manuscripts, 247 abstracts, 20 book chapters, 13 review articles, 7 editorials in the fields of evaluating atheroma, drug and gene delivery and cardiovascular dynamics. He is the co- editor of the textbook. "Non-invasive Imaging of Atherosclerosis".
		Renata Pasqualini Buchanan & Seeger Professor Medicine and Cancer Biology The University of Texas M. D. Anderson Cancer Center Renata Pasqualini, Ph.D. is the Buchanan & Seeger Professor of Medicine and Cancer Biology at The University of Texas M. D. Anderson Cancer Center. She received her Ph.D. degree in Biochemistry at the Ludwig Institute for Cancer Research, São Paulo Branch from the University of São Paulo, Brazil. She pursued postdoctoral training at Children's Hospital of Boston and at Dana Farber Cancer Institute, Harvard Medical School and at the Burnham Institute in La Jolla. Dr. Pasqualini is an internationally recognized expert in vascular biology, metastasis, and angiogenesis. She has originally co-developed in vivo phage display. This technology enables combinatorial mapping of tissue and disease-specific molecular addresses in vivo, allowing for the development of ligand-directed targeted delivery of therapeutic and imaging agents. Dr. Pasqualini has a close and longstanding scientific collaboration with Dr. Wadih Arap; together, they run a large research laboratory with several graduate and medical students, postdoctoral fellows, and technical and clerical staff. She serves on grant review boards for several national and international funding agencies. Drs. Arap and Pasqualini lead an active drug development program. "Safe to proceed" status for their first Investigational New Drug application has recently been granted by the Food & Drug Administration.
		Anil K. Sood Professor and Director Blanton-Davis Ovarian Cancer Research Program Departments of Gynecologic Oncology and Cancer Biology The University of Texas M.D. Anderson Cancer Center Dr. Sood is Professor and Director of the Blanton-Davis Ovarian Cancer Research Program in the Departments of Gynecologic Oncology and Cancer Biology at the M. D. Anderson Cancer Center. His research is focused in three main areas: 1) development of new strategies for systemic in vivo siRNA delivery using biocompatible nanoparticles; 2) effect of neuroendocrine stress hormones on ovarian cancer growth and progression; and 3) development of novel anti-vascular therapeutic approaches. Dr. Sood has published numerous peer-reviewed articles and has authored and co-authored several book chapters. Dr. Sood has received major recognition for his research accomplishments including the Gynecologic Cancer Foundation/Margaret Greenfield/Carmel Cohen, M.D. "Excellence in Ovarian Cancer Research Award".