Robert Blumenthal, Ph.D.
Dr. Blumenthal pioneered biophysical approaches to studies in the areas of membrane transport, ion channels, membrane domains, signaling and viral entry. As Head of the Membrane Structure and Function Section, Dr. Blumenthal conducted research on lipid-based nanocapsules and triggered chemotherapy and, and on mechanisms of viral fusion and inactivation. He used liposomes as model membranes to study various aspects of membrane structure and function. The insights gleaned from these studies led to the design of temperature-sensitive liposomes, which are currently being investigated in clinical trials. Dr. Blumenthal retired from active research in 2012 and is currently Scientist Emeritus.
1) membrane biophysics, 2) viral fusion, 3) liposomes, 4) fluorescence, 5) membrane modeling, 6) HIV entry into cells
Dr. Blumenthal is an internationally recognized scientist in the areas of membranes, viruses, cell biology and biophysics. He has expanded the discipline of biophysics to various areas of biology. Signal contributions include:
- Analysis of coupling between membrane transport and bioenergetics in a model system based on irreversible thermodynamics, which led to a better understanding of the coupling of the two processes in biological systems.
- New insights into membrane patterning based on allostery and cooperativity
- Analysis of kinetics of opening and closing of single channels in lipid bilayers that forms the basis of single channel analysis in biological membranes
- Pioneered development of fluorescent assays for liposome permeability and fusion that are widely used in the field
- Pioneered the design of temperature-sensitive liposomes, which are currently being investigated in clinical trials
- Demonstrated that the region of the tight junction between apical and basolateral surfaces in epithelial cells can act as a selective barrier to lateral diffusion of membrane lipids and proteins. These observations form the basis for studies on membrane trafficking, sorting and domain formation.
- Showed that an important component of T cell-mediated cytoxicity is the release of cytolysins from T cell granules, which form pores in susceptible target cell membranes
- Demonstrated translocation of certain proteins across membranes under the influence of an electric field
- Developed insights and methodologies for the reconstitution of viral envelope proteins and receptors into lipid membranes
- Developed the use of fluorescence dequenching measurements to follow viral membrane fusion events in real time
- Pioneered measurements of single virus-cell fusion events observed by Fluorescence Video Microscopy
- Provided basic insights into mechanisms of viral fusion by developing novel fluorescent methods based on differential distribution of lipids and cytoplasmic markers that revealed crucial stages of viral envelope glycoprotein-induced cell fusion
- Pioneered observations of early intermediated in viral envelope protein-mediated fusion that involves conformational changes of the envelope glycoproteins
- Showed that the mode of entry of HIV entry inhibitors is linked to the kinetics of HIV fusion
- Pioneered investigations of the role of glycosphingolipids and domains in the target plasma membrane in mediating HIV entry
- Pioneered photosensitized labeling of techniques to study viral entry into cells
Dr. Blumenthal has built bridges between the various areas of physics, chemistry and biology by organizing conferences and workshops that link these disciplines. As chair of the membrane biophysics subgroups he has organized a session on translocation of proteins across membranes and he organized various satellite workshops on membrane fusion associated with national and international biophysics meetings. In 1995 he was a co-organizer of a Fogarty Center meeting on domain organization in biological membranes and in the early 2000’s he organized four highly influential workshops on viral entry, which brought together virologists, immunologists, cell biologists, structural biologists and biophysicists. He had also launched Nanobiology Seminar Series and workshops at NCI featuring distinguished scientists who pioneered the application of Nanotechnology to Cancer Research.
Dr. Blumenthal was the founder of the Center for Cancer Research Nanobiology Program (CCRNP), which promoted multidisciplinary research aimed at developing tools for nanoscale, biologically-based strategies to prevent, diagnose, and treat cancer, AIDS, and biodefense-related viral diseases. He served as the director of the program and was an intramural representative of the NIH-wide Nano Task Force, a component of the NIH Roadmap. As a task force member, he has helped identify unique roles for the NIH in the development of NIH-relevant nanotechnology.
Selected Key Publications
Initial stages of influenza hemagglutinin-induced cell fusion monitored simultaneously by two fluorescent events: cytoplasmic continuity and lipid mixing. .J. Cell Biol.. 109: 13-122, 1989. [ Journal Article ]
Dilation of the human immunodeficiency virus-1 envelope glycoprotein fusion pore revealed by the inhibitory action of a synthetic peptide from gp41..J. Cell Biol.. 140: 315-323, 1998. [ Journal Article ]
- Journal of Membrane Biology. 1: 351-374, 1970. [ Journal Article ]
Interaction of lymphocytes with lipid bilayer membranes: a model for lymphocyte-mediated lysis of target cells..Proc Natl Acad Sci U S A.. 7: 2789-2793, 1975. [ Journal Article ]
- Science. 202: 1290-1293, 1978. [ Journal Article ]
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 studying mechanisms of active transport across membranes. Following postdoctoral work at the Institute Pasteur and at Columbia University studying molecular mechanisms of membrane excitability in neurons, he came to the NIH and was ultimately recruited by the NCI. In 1978 he was tenured and in 1980 he became chief of the Section on Membrane Structure and Function. In 2005 he was appointed director of the newly established Center for Cancer Research Nanobiology Program. Dr. Blumenthal is the 2008 recipient of the NIH Merit Award in recognition of his vision and leadership in establishing the CCR Nanobiology Program, which promotes multidisciplinary research in cancer, AIDS, and viral diseases. Dr. Blumenthal also received the NCI Directors' 2008 Mentor of Merit award. Dr. Blumenthal has worked in a wide range of areas in membrane biophysics, which includes membrane fusion, membrane transport, membrane domains, membrane channels, cell surface receptors, immune cytotoxic mechanisms, and use of liposomes for delivery of drugs and genes into cells. Prior to his retirement in 2012, Dr. Blumenthal's most recent interest was in viral entry, pathogenesis and vaccines; multifunctional nanoparticles for triggered and targeted delivery of therapeutics; and photo-induced chemical reactions in membranes.