Robert  Blumenthal, Ph.D.
Robert Blumenthal, Ph.D.
Scientist Emeritus

Center for Cancer Research
National Cancer Institute

Building 469, Room 246A
Frederick, MD 21702-1201
301-846-1446

Dr. Blumenthal pioneered biophysical approaches to studies in the areas of membrane transport, ion channels, membrane domains, signaling and viral entry. He uses 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. Currently, Dr. Blumenthal is developing photo-activated liposomes for cancer therapy applications.

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.

Areas of Expertise
1) membrane biophysics, 2) viral fusion, 3) liposomes, 4) fluorescence, 5) membrane modeling, 6) HIV entry into cells

Lipid-based Nanocapsules and Triggered Chemotherapy. Our goal is to construct cancer treatment modalities based on the preferential accumulation of drugs and therapeutic agents in tumor sites resulting in enhanced killing of cancer cells. We implement a multi-pronged approach towards this goal. 1. We have developed Radiation Induced and Targeted Chemotherapy (RITCH) for cancer treatment using small hydrophobic molecules that can be turned into tumor killing toxic compounds by targeted radiation and ultrasound. 2. We have designed multifunctional lipid-based nanoparticles that specifically target cancer cells and release their payload when triggered by light or heat. 3. Using lipid model membranes we are investigating mechanisms by which beta hairpin peptides designed by Dr Joel Schneider (CBL, CCR, NCI) exhibiting ant-cancer activity cause membrane damage leading to killing of cancer cells.

Mechanisms of Viral Fusion and Inactivation. Our overall approach is to kinetically resolve steps in the pathway of viral envelope glycoprotein-mediated membrane fusion and to uncover physical parameters underlying those steps using a variety of biochemical, biophysical, virological, and molecular and cell biological techniques in vitro studies with infectious virus and HIV envelope proteins expressed in cells. We are using peptide-based entry inhibitors linked to specific lipids to probe details of the fusion reaction. We have recently shown that conjugation of sphinganine (a precursor of dehydrospingomyelin) confers a striking specificity to the inhibitory potential of a short HIV-based peptide suggesting that sphingopeptides act as double edged swords with both lipid and peptide playing a role in the inhibition of HIV entry. We have developed novel methodologies to study fusion based on photo-induced chemical reactions in the membrane using hydrophobic probes such as Iodonaphtylazide. We are applying this methodology both in the analytical mode (identification of domains of viral proteins and of receptors involved in fusion) and the functional mode (affecting viral protein-induced fusion). Using photo-reactive hydrophobic probes we have found ways to inactivate viral envelope glycoproteins while leaving their overall structures intact. These studies have important implications for anti-viral therapies and vaccine development.

Scientific Focus Areas:
Biomedical Engineering and Biophysics, Cell Biology, Chemical Biology, Structural Biology, Virology
Selected Publications
  1. Kim T, Afonin KA, Viard M, Koyfman AY, Sparks S, Heldman E, Grinberg S, Linder C, Blumenthal RP, Shapiro BA.
    Mol Ther Nucleic Acids. 2: e80, 2013. [ Journal Article ]
  2. Yavlovich A, Viard M, Gupta K, Sine J, Vu M, Blumenthal R, Tata DB, Puri A.
    Int J Nanomedicine. 8: 2575-87, 2013. [ Journal Article ]
  3. Klug YA, Ashkenazi A, Viard M, Porat Z, Blumenthal R, Shai Y.
    Biochem. J.. 461: 213-22, 2014. [ Journal Article ]
  4. Afonin KA, Viard M, Martins AN, Lockett SJ, Maciag AE, Freed EO, Heldman E, Jaeger L, Blumenthal R, Shapiro BA.
    Nat Nanotechnol. 8: 296-304, 2013. [ Journal Article ]
  5. Afonin KA, Desai R, Viard M, Kireeva ML, Bindewald E, Case CL, Maciag AE, Kasprzak WK, Kim T, Sappe A, Stepler M, Kewalramani VN, Kashlev M, Blumenthal R, Shapiro BA.
    Nucleic Acids Res.. 2013. [ 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. Dr. Blumenthal's current interest is in viral entry, pathogenesis and vaccines; multifunctional nanoparticles for triggered and targeted delivery of therapeutics; and photo-induced chemical reactions in membranes.

Name Position
Sophie Dean Summer Student
Sai Janani Ganesan Predoctoral Fellow
Patrick Hall Summer Student
Anu Puri Ph.D. Staff Scientist
Henry Reichard Summer Student
Derek Thayer Postbaccalaureate Fellow
Mathias Viard Ph.D. Staff Scientist (Contr)

Summary

Dr. Blumenthal pioneered biophysical approaches to studies in the areas of membrane transport, ion channels, membrane domains, signaling and viral entry. He uses 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. Currently, Dr. Blumenthal is developing photo-activated liposomes for cancer therapy applications.

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.

Areas of Expertise
1) membrane biophysics, 2) viral fusion, 3) liposomes, 4) fluorescence, 5) membrane modeling, 6) HIV entry into cells

Research

Lipid-based Nanocapsules and Triggered Chemotherapy. Our goal is to construct cancer treatment modalities based on the preferential accumulation of drugs and therapeutic agents in tumor sites resulting in enhanced killing of cancer cells. We implement a multi-pronged approach towards this goal. 1. We have developed Radiation Induced and Targeted Chemotherapy (RITCH) for cancer treatment using small hydrophobic molecules that can be turned into tumor killing toxic compounds by targeted radiation and ultrasound. 2. We have designed multifunctional lipid-based nanoparticles that specifically target cancer cells and release their payload when triggered by light or heat. 3. Using lipid model membranes we are investigating mechanisms by which beta hairpin peptides designed by Dr Joel Schneider (CBL, CCR, NCI) exhibiting ant-cancer activity cause membrane damage leading to killing of cancer cells.

Mechanisms of Viral Fusion and Inactivation. Our overall approach is to kinetically resolve steps in the pathway of viral envelope glycoprotein-mediated membrane fusion and to uncover physical parameters underlying those steps using a variety of biochemical, biophysical, virological, and molecular and cell biological techniques in vitro studies with infectious virus and HIV envelope proteins expressed in cells. We are using peptide-based entry inhibitors linked to specific lipids to probe details of the fusion reaction. We have recently shown that conjugation of sphinganine (a precursor of dehydrospingomyelin) confers a striking specificity to the inhibitory potential of a short HIV-based peptide suggesting that sphingopeptides act as double edged swords with both lipid and peptide playing a role in the inhibition of HIV entry. We have developed novel methodologies to study fusion based on photo-induced chemical reactions in the membrane using hydrophobic probes such as Iodonaphtylazide. We are applying this methodology both in the analytical mode (identification of domains of viral proteins and of receptors involved in fusion) and the functional mode (affecting viral protein-induced fusion). Using photo-reactive hydrophobic probes we have found ways to inactivate viral envelope glycoproteins while leaving their overall structures intact. These studies have important implications for anti-viral therapies and vaccine development.

Scientific Focus Areas:
Biomedical Engineering and Biophysics, Cell Biology, Chemical Biology, Structural Biology, Virology

Publications

Selected Publications
  1. Kim T, Afonin KA, Viard M, Koyfman AY, Sparks S, Heldman E, Grinberg S, Linder C, Blumenthal RP, Shapiro BA.
    Mol Ther Nucleic Acids. 2: e80, 2013. [ Journal Article ]
  2. Yavlovich A, Viard M, Gupta K, Sine J, Vu M, Blumenthal R, Tata DB, Puri A.
    Int J Nanomedicine. 8: 2575-87, 2013. [ Journal Article ]
  3. Klug YA, Ashkenazi A, Viard M, Porat Z, Blumenthal R, Shai Y.
    Biochem. J.. 461: 213-22, 2014. [ Journal Article ]
  4. Afonin KA, Viard M, Martins AN, Lockett SJ, Maciag AE, Freed EO, Heldman E, Jaeger L, Blumenthal R, Shapiro BA.
    Nat Nanotechnol. 8: 296-304, 2013. [ Journal Article ]
  5. Afonin KA, Desai R, Viard M, Kireeva ML, Bindewald E, Case CL, Maciag AE, Kasprzak WK, Kim T, Sappe A, Stepler M, Kewalramani VN, Kashlev M, Blumenthal R, Shapiro BA.
    Nucleic Acids Res.. 2013. [ Journal Article ]

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 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. Dr. Blumenthal's current interest is in viral entry, pathogenesis and vaccines; multifunctional nanoparticles for triggered and targeted delivery of therapeutics; and photo-induced chemical reactions in membranes.

Team

Name Position
Sophie Dean Summer Student
Sai Janani Ganesan Predoctoral Fellow
Patrick Hall Summer Student
Anu Puri Ph.D. Staff Scientist
Henry Reichard Summer Student
Derek Thayer Postbaccalaureate Fellow
Mathias Viard Ph.D. Staff Scientist (Contr)