Our Science – Blumenthal Website

Robert Blumenthal, Ph.D.

CCR Nanobiology Program Head, Membrane Structure and Function Section Program Director Building 469, Room 152 NCI-Frederick Frederick, MD 21702-1201 Phone:   301-846-5532 Fax:   301-846-5598 E-Mail:   BlumenthalR@mail.nih.gov

Biography

Dr. Blumenthal obtained his M.Sc. at the University of Leiden, The Netherlands, and his Ph.D. in physical chemistry at the Weizmann Institute, Israel. Following postdoctoral work at the Institute Pasteur and at Columbia University, he came to the NIH and was ultimately recruited by the NCI. In 1980 he became chief of the Section on Membrane Structure and Function, a position he currently holds as a Senior Biomedical Research Scientist. He also serves as the director of the CCR Nanobiology Program. Dr. Blumenthal has worked in a wide range of areas in membrane biophysics, which includes membrane fusion, membrane transport, cell surface receptors, immune cytotoxic mechanisms, and use of liposomes for delivery of drugs and genes into cells. Dr. Blumenthal's current interest is in the biology of virus and nanoparticle entry into cells and tissues.

Research

Regulation of Membrane Fusion by Viral and Cellular Proteins and Lipids
Specific fusion of biological membranes is a central requirement for many cellular processes. Membrane fusion involves the merging of the membranes of two different organelles and the mixing of aqueous compartments encapsulated by these membranes. Enveloped animal viruses deliver their genetic material to the cell by fusion of their membranes with those of the target cell. Although we study mechanisms of viral entry using a variety of viruses including Vesicular Stomatitis Virus, Influenza Virus, and Sendai Virus, our main focus during the past years has been directed towards HIV/SIV entry. The envelope glycoproteins of these various viruses accomplish the same task, membrane fusion, and studies on any one of these is likely to help clarify how others function as well. Viral fusion is a complex process whose elucidation requires the understanding of a range issues in membrane structure and function, which include membrane receptors, conformational changes of proteins, protein-lipid interactions, chemistry and physics of lipids and membrane micro-domains. Our program employs a breadth of techniques and experimental systems to study the fusion process, which include biophysical approaches (spectrofluorometry, quantitative light microscopy, photosensitized labeling, proteomics) as well as virological, cell biological and molecular biological methodologies. Our efforts to unravel mechanisms of viral entry has lead us into cancer biological directions, specifically dealing with issues related to membrane receptor signaling, trafficking and clustering into micro-domains. Currently, the overall goal of our research program is to elucidate mechanisms of viral fusion. The complex kinetics of viral fusion indicates that the system has to undergo a series of distinct steps before the final fusion event can occur. Our approach is to dissect these steps and analyze underlying molecular parameters underlying the kinetic intermediates. Resolution of the structure of such intermediates will yield insights into the mode of action of membrane fusion-inducing proteins. The knowledge gained will then be applied to the design of inhibitors of viral entry and of vaccines that prevent viral infection.
As we transition to the CCR Nanobiology Program, we are planning and designing experiments on the lipid-based nanocapsules and nano fusion machines. We believe that our knowledge and skills in elucidating mechanisms of viral entry will be of benefit to find new ways to deliver anti-cancer drugs. The anticipated projects include design and study of multifunctional liposomes bearing drugs (e.g. toxic or anti-inflammatory substances), conjugated with a disease-specific targeting agent (e.g. antibodies), and labeled with imaging agents. We plan to use external sources of energy (X-rays, light, microwave, ultrasound) for controlled disruption of liposomes at the optimal time and within a limited volume. The liposomes will be protected by polymers or polymerized lipids and modified to allow controlled disruption. We plan to exploit a new class of fusion-associated small transmembrane (FAST) proteins to build nano fusion machines that will directly deliver their cargo to the cells' cytoplasm.

This page was last updated on 6/11/2008.