Maurizio Pellecchia, Ph.D.

Sanford|Burnham
Medical Research Institute

Research Focus
Dr. Pellecchia’s research focuses on the characterization of intermolecular interactions, on the determination of protein structures and on the development of small molecule inhibitors of protein targets involved in cell-signaling, virulence factors and host-pathogens interactions. The resulting compounds are then used as molecular probes to provide further understanding on the mechanism of action of their respective targets. The overall goal of the laboratory is to successfully bring together basic sciences involving modern nuclear magnetic resonance spectroscopy (NMR) techniques, computer modeling and traditional medicinal chemistry to elucidate the molecular basis of disease and to develop novel therapeutic compounds. Amongst the several projects that Dr. Pellecchia’s laboratory have initiated in the past years, noteworthy are the discovery, characterization and further development of potential therapeutic compounds targeting proteins of the Bcl-2 family, such as Bcl-xL and Bcl-2 (cancer targets) as well as Bid (involved in neurodegenerative diseases) and protein kinases such as p38 and Jnk (inflammation and diabetes). In addition, other very active areas of research involve the development of antitoxin compounds targeting the Anthrax metalloproteinase LF and protein components of the type-III secretion system, common to many pathogens, including Yersinia pestis and Salmonella. Finally, an area in which Dr. Pellecchia remains particularly interested is the development of novel NMR-based techniques to aid the characterization of protein structure, protein-protein and protein-ligand interactions using NMR spectroscopy. The design and synthesis of several high affinity ligands, for example, was made possible by the SAR by ILOEs approach, a NMR-based method developed in Dr. Pellecchia’s laboratory that enables the identification of high affinity ligands for a given protein target.

Biography
Dr. Pellecchia is a medicinal chemist with a strong background in biophysics and NMR-based drug design. He trained at the University of Naples (Italy) where he obtained his Ph.D. in Pharmaceutical Sciences, at the ETH-Zurich (working with 2002 Nobel Laureate Prof. Dr. Kurt Wüthrich) and the University of Michigan. Prior to his recruitment at The Burnham Institute as Associate Professor, Dr. Pellecchia spent a few years in the pharmaceutical industry. Dr. Pellecchia’s laboratory is centered on the characterization of intermolecular interactions, protein structure and on the development of small molecule inhibitors in systems involved in cell-signaling and apoptosis for the treatment of several human diseases including cancer, neurodegeneration and infectious diseases.

Tomas Mustelin, Ph.D.

RIA MedImmune

Research Focus
Dr. Mustelin investigates a family of genes called protein tyrosine phosphatase (PTPases), many of which act as tumor suppressors in numerous types of human cancer. It is anticipated that damage or loss of many additional family members will be found to underlay human disease, particularly cancers of white blood cells (e.g. leukemias and lymphomas). Dr. Mustelin has generated the tools to study some 35 different PTPases, representing nearly half of the genes in this family in the human genome. Dr. Mustelin's work aims at understanding the exact function of each of these PTPases in the cell's machinery for growth, survival, and death, in the white blood cell system. The results of Dr. Mustelin's research will help him and others to design rational approaches for the combat of cancer.

Biography
Tomas Mustelin earned his M.D. and Ph.D. degrees from University of Helsinki in 1987. He trained as a postdoctoral fellow at The Scripps Research Institute in La Jolla, 1988-1990. Dr. Mustelin returned to Finland for two years in clinical practice and research as a Junior Scientist with the Finnish Academy of Sciences at University of Helsinki. He was appointed Docent at University of Helsinki in 1992, an appointment he maintains to this day. From 1992-1998, Dr. Mustelin worked at La Jolla Institute of Allergy and Immunology in San Diego, as Assistant, then Associate Member. He was affiliated briefly with the Sidney Kimmel Cancer Center in San Diego prior to his recruitment to The Burnham Institute in September 1999. In 2007 he was recruited at Amgen Corp. as Vice President of Drug Discovery and Inflammation Research.

Sanford|Burnham
Medical Research Institute

Research Focus
Dr. Aza-Blanc’s work covers applications of Cell-based Functional-Genomics technology, such as loss-of function and gain-of-function screening, in basic and translational research. Most of his work focuses on high-throughput RNAi screening methodology, which enables researchers to emulate forward-genetics approaches in cells and identify genes by virtue of their function. Under his direction, the RNAi screening core at Burnham applies this technology in multiple research fields including cancer, stem cell biology, virology, and metabolism. HTS-RNAi allows the identification of cellular components mediating specific cellular functions. Currently, much of Dr. Aza-Blanc’s effort is dedicated to characterize the mode of action of pro-apoptotic agents such as extracellular surveillance factors, natural toxins, and cytotoxic compounds with potential for cancer treatment. By performing siRNA screens, it is possible to identify the genes that mediate or prevent these agents activity. This information can then be computationally matched to known and predicted cellular networks to define the agent’s mechanism of action. When the technology is applied to compounds (compound activity profiling) the information generated can lead to identification of the agent’s target and detection of unexpected off-target activities. The goal of this approach is to allow better informed decisions during lead selection early in the drug discovery process.

Biography
Dr Aza-Blanc earned his Ph.D. degree in the Universidad Autonoma de Madrid in 1994 working in the field of Molecular Endocrinology. In 1995, he moved to San Francisco where he trained in developmental biology at the University of California-San Francisco under the supervision of Dr. Thomas Kornberg. Focused on the signaling mechanisms regulating morphogenesis in Drosophila, he made significant contributions to the understanding of the morphogenic activity of the Hedgehog signaling cascade. In 1999, he joined the Genomics Institute of Novartis in San Diego where he became interested in High throughput technologies. First as a institute fellow and then as a Principal Investigator in the Genomics Department, he performed pioneering work in the early days of RNAi such as the development of the first algorithms for improved siRNA performance, the creation of the first siRNA libraries, and the application of high-throughput RNAi screening technology in target discovery and validation. His work resulted in the first publication describing RNAi screening as a discovery tool in mammalian systems. He was recruited to the Burnham Institute in 2006 to launch the Functional Genomics Core, where he currently serves as Director of Functional Genomics Resources. He is an expert in cell-based assays and HTS technology, and has given numerous lectures and published several articles on the subject. Altogether, Dr. Aza-Blanc has more than 8 years of experience on RNAi applications both in academic and industrial environments.

Jeff Price, M.D., Ph.D.

Sanford|Burnham
Medical Research Institute

Research Focus
The central theme is the development of fully automated quantitative microscopy, or scanning cytometry, for biomedical applications. The instrumentation research areas include high performance autofocus, real-time image segmentation and image fluorometry. These are key components for a scanning cytometer capable of accurate, exhaustive analyses of the 100,000 – 10,000,000 cells on a single microscope slide at optical resolution (usually ≤ 0.5 x 0.5 mm2 pixels). Quantifying the measurement accuracy and/or precision of each step in the scanning cytometry process (e.g., autofocus followed by image segmentation, fluorometry and cell classification) are key components of the research. Current and proposed biomedical research areas include cervical (Pap smear) cancer screening, rare event detection (e.g., locating fetal cells in maternal circulation for genotyping), and chemotherapy testing using time-lapse scanning cytometry of living cells cultured on the microscope stage.

Biography
Jeffrey H. Price received his M.D. degree from Loma Linda University, Loma Linda, CA, in 1985, and his Ph.D. degree in bioengineering from the University of California, San Diego, in 1990, where he also received his postdoctoral training. In 1993, he was appointed Assistant Project Scientist and, in 1996, Associate Research Scientist. From 1994 to 2004 he directed the NSF-Whitaker Quantitative Imaging and Confocal Microscopy Resource in Bioengineering at UCSD. In 1999 he founded Q3DM, Inc., which marketed his research group’s high throughput microscopy inventions for cell-image-based screening, and which was purchased by Beckman Coulter, Inc. in 2003. In 2004 he Co-Founded Vala Sciences Inc, which develops and markets software and kits for cell-image based assays. He was recruited to the position of Associate Professor at The Burnham Institute in 2004, where he is a member of the Signal Transduction and Stem Cells and Regeneration Research Programs. With its collaborators, his laboratory is focused on automated analytical microscopy research for tissue proteomics, tracking of cell migration and differentiation, and rare cell diagnostics.

Distinguished Professor

Sanford|Burnham
Medical Research Institute

Research Focus
The Ruoslahti laboratory studies peptides that home to specific targets in the body, such as tumors, atherosclerotic plaques and wound tissue. These peptides, which usually bind to receptors in the vessels of the target tissue, can be used to selectively deliver diagnostic probes and drugs to the target. The latest development is the discovery of homing peptides with tumor-penetrating properties.  The current focus is on enhancing the effects of coupled and co-injected drugs with the tumor-homing peptides, particularly in mouse models of breast cancer. This laboratory also studies the receptors for the peptides and the workings of their tumor penetration activity.
 

Biography

Erkki Ruoslahti earned his M.D. and Ph.D. from the University of Helsinki in Finland in 1967. After postdoctoral training at the California Institute of Technology, he held various academic appointments with the University of Helsinki and the University of Turku in Finland and City of Hope National Medical Center in Duarte, California. He joined Sanford-Burnham in 1979 and served as its President from 1989-2002. He has been a Distinguished Professor at UCSB in Biological Sciences since 2005. His honors include: elected membership to the U.S. National Academy of Sciences, Institute of Medicine, American Academy of Arts and Sciences, and the European Molecular Biology Organization. He is the recipient of the G.H.A. Clowes Award, Robert J. and Claire Pasarow Foundation Award, Jacobaeus International Prize, The Jubilee Award given by the British Biomedical Society. He was a Nobel Fellow at the Karolinska Institute in Stockholm in 1995, and is an Honorary Doctor of Medicine from the University of Lund, as well as a Knight of the Order of the White Rose of Finland. Dr. Ruoslahti is the recipient of the 2005 Japan Prize in Cell Biology.

MDDT course 2010

MDDT course 2009

MDDT course 2008

MDDT course 2007