David S. Cafiso
Encyclopedia
David S. Cafiso is an American biochemist
and a Professor of Chemistry at the University of Virginia
. His research focuses on membrane proteins and cell signaling, and is primarily supported by grants from the National Institute of Health.
and peripheral and integral membrane proteins.
One area of investigation involves studies on the mechanisms by which proteins become attached to membrane surfaces. Attachment is critical for cell-signaling because it controls protein-protein interactions and the access of enzymes to lipid
substrates. For example, the oncogenic form of the src tyrosine kinase
is not active and fails to transform cells until it becomes attached to the cytoplasmic face of the plasma membrane. The laboratory is currently determining the structure and electrostatic interactions made by highly positively charged protein motifs, such as those from MARCKS
(the myristoylated alanine rich C-kinase substrate) with negatively charged lipid surfaces. In addition to regulating membrane attachment, these positively charged motifs function to sequester phosphatidylinositol 4,5, bisphosphate (PIP2), and regulate the activity of this phosphorylated inositol lipid within the cytoplasmic membrane. Dr. Cafiso is also interested in determining the membrane interactions made by protein domains such as C2 domains, which are found in a wide range of proteins involved in cell signaling
. C2 domains function to attach their parent proteins to membranes in a Ca ++ dependent fashion. C2 domains perform critical roles in membrane trafficking, membrane fusion and membrane repair, and defects in these domains result in forms of muscular dystrophy and deafness.
A second area of investigation involves membrane transport
. Dr. Cafiso's laboratory is currently examining the molecular mechanisms that function to facilitate active transport. For example, he is interested in determining the molecular mechanisms by which BtuB transports vitamin B12
across the outer membrane of Escherichia coli. This protein is homologous to FecA, FepA and FhuA, outer membrane iron transport proteins that presumably function by similar mechanisms. These proteins belong to a class of transport proteins for which high-resolution structural models have been obtained, and they are extremely important for the survival of some bacterial pathogens. In addition to BtuB, FecA and FhuA, we are presently expressing, reconstituting and labeling BtuC/D. This protein is member of the ABC cassette transporter family and it is responsible for carrying vitamin B12 across the inner membrane.
The primary tools that Dr. Cafiso uses in his research include EPR spectroscopy
and high-resolution NMR. Site-directed spin labeling
is a powerful methodology that combines site-directed mutagenesis with and EPR spectroscopy
. Dr. Cafiso is developing and making use of this tool, which is particularly well-suited to address questions regarding the dynamics and molecular function of membrane proteins.
Univ. of California, Berkeley, Calif. Ph.D. 1979 Biophysics
Univ. of California, Berkeley, Calif. 1979 - 1980 Postdoctoral Study
Stanford University, Stanford, Calif. 1980 - 1981 Postdoctoral Study
Camille and Henry Dreyfus Award for Distinguished New Faculty in Chemistry, 1981.
Member, NSF Biophysics Panel, 1990-1993. Member, NIH IRG Study Section.
Adhoc member, NIH BBCB study section, 1996–present.
NIH Biomembranes Study Section, 2005.
Editorial Board, Biophysical Journal.
Editorial Board, Journal of Liposome Research.
Editorial Board, Cell Biochemistry and Biophysics.
Biophysical Society: 1978–present.
American Society for the Advancement of Science: 1980–present.
American Chemical Society: 1981–present.
Faculty of 1000 contributor, 2001–present.
Biochemist
Biochemists are scientists who are trained in biochemistry. Typical biochemists study chemical processes and chemical transformations in living organisms. The prefix of "bio" in "biochemist" can be understood as a fusion of "biological chemist."-Role:...
and a Professor of Chemistry at the University of Virginia
University of Virginia
The University of Virginia is a public research university located in Charlottesville, Virginia, United States, founded by Thomas Jefferson...
. His research focuses on membrane proteins and cell signaling, and is primarily supported by grants from the National Institute of Health.
Research
Work in Dr. Cafiso's laboratory is directed at studying membranesBiological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
and peripheral and integral membrane proteins.
One area of investigation involves studies on the mechanisms by which proteins become attached to membrane surfaces. Attachment is critical for cell-signaling because it controls protein-protein interactions and the access of enzymes to lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
substrates. For example, the oncogenic form of the src tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
is not active and fails to transform cells until it becomes attached to the cytoplasmic face of the plasma membrane. The laboratory is currently determining the structure and electrostatic interactions made by highly positively charged protein motifs, such as those from MARCKS
MARCKS protein
MARCKS proteins play important roles in cell shape, cell motility, secretion, transmembrane transport, and regulation of the cell cycle...
(the myristoylated alanine rich C-kinase substrate) with negatively charged lipid surfaces. In addition to regulating membrane attachment, these positively charged motifs function to sequester phosphatidylinositol 4,5, bisphosphate (PIP2), and regulate the activity of this phosphorylated inositol lipid within the cytoplasmic membrane. Dr. Cafiso is also interested in determining the membrane interactions made by protein domains such as C2 domains, which are found in a wide range of proteins involved in cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
. C2 domains function to attach their parent proteins to membranes in a Ca ++ dependent fashion. C2 domains perform critical roles in membrane trafficking, membrane fusion and membrane repair, and defects in these domains result in forms of muscular dystrophy and deafness.
A second area of investigation involves membrane transport
Membrane transport
In cellular biology the term membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes namely lipid bilayers that contain proteins embedded in them...
. Dr. Cafiso's laboratory is currently examining the molecular mechanisms that function to facilitate active transport. For example, he is interested in determining the molecular mechanisms by which BtuB transports vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
across the outer membrane of Escherichia coli. This protein is homologous to FecA, FepA and FhuA, outer membrane iron transport proteins that presumably function by similar mechanisms. These proteins belong to a class of transport proteins for which high-resolution structural models have been obtained, and they are extremely important for the survival of some bacterial pathogens. In addition to BtuB, FecA and FhuA, we are presently expressing, reconstituting and labeling BtuC/D. This protein is member of the ABC cassette transporter family and it is responsible for carrying vitamin B12 across the inner membrane.
The primary tools that Dr. Cafiso uses in his research include EPR spectroscopy
Electron paramagnetic resonance
Electron paramagnetic resonance or electron spin resonance spectroscopyis a technique for studying chemical species that have one or more unpaired electrons, such as organic and inorganic free radicals or inorganic complexes possessing a transition metal ion...
and high-resolution NMR. Site-directed spin labeling
Site-directed spin labeling
Site-directed spin labeling is a technique for investigating protein local dynamics using electron spin resonance. The theory of SDSL is based on the specific reaction of spin labels with amino acids. A spin label's built-in protein structure can be detected by EPR spectroscopy...
is a powerful methodology that combines site-directed mutagenesis with and EPR spectroscopy
Electron paramagnetic resonance
Electron paramagnetic resonance or electron spin resonance spectroscopyis a technique for studying chemical species that have one or more unpaired electrons, such as organic and inorganic free radicals or inorganic complexes possessing a transition metal ion...
. Dr. Cafiso is developing and making use of this tool, which is particularly well-suited to address questions regarding the dynamics and molecular function of membrane proteins.
Education and training
Univ. of California, Berkeley, Calif. A.B. 1974 BiophysicsUniv. of California, Berkeley, Calif. Ph.D. 1979 Biophysics
Univ. of California, Berkeley, Calif. 1979 - 1980 Postdoctoral Study
Stanford University, Stanford, Calif. 1980 - 1981 Postdoctoral Study
Societies, service, and honors
Jane Coffin Childs Foundation Fellow, 1979-1981.Camille and Henry Dreyfus Award for Distinguished New Faculty in Chemistry, 1981.
Member, NSF Biophysics Panel, 1990-1993. Member, NIH IRG Study Section.
Adhoc member, NIH BBCB study section, 1996–present.
NIH Biomembranes Study Section, 2005.
Editorial Board, Biophysical Journal.
Editorial Board, Journal of Liposome Research.
Editorial Board, Cell Biochemistry and Biophysics.
Biophysical Society: 1978–present.
American Society for the Advancement of Science: 1980–present.
American Chemical Society: 1981–present.
Faculty of 1000 contributor, 2001–present.
External links
- http://ernst.chem.virginia.edu/dsclab/