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Henri
Brunengraber, MD, PhD is
seeking post-doctoral trainees with experience in metabolic
investigations (in vivo or in vitro)
using stable isotopes and GC-MS. |
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Research
projects are briefly outlined
as follows:
(i) Regulation
of gluconeogenesis in health
and disease, investigated either
with 13C-labeled
tracers and mass isotopomer distribution
analysis, or with 2H2O
and 2H-incorporation
in glucose carbons
Previs,
S. F.,
Fernandez, C. A., Yang,
D., Soloviev,
M. V.,
David, F., and Brunengraber,
H. Limitations
of mass
isotopomer distribution
analysis
of glucose
to study
gluconeogenesis:
Substrate
cycling
between glycerol
and triosephosphates
in liver. J.
Biol.
Chem. 270: 19806-19815
(1995).
Hazey,
J.
W.,
Yang,
D., Powers,
L., Previs, S. F., David, F., Beaulieu, A.
D., Puchowicz,
M., Potter, J. F., Palmquist, D. L., and Brunengraber,
H. Tracing gluconeogenesis with deuterated
water: measurement of low deuterium enrichments
on carbons 6 and 2 of glucose. Anal.
Biochem. 248: 158-67
(1997).
Brunengraber, H., Kelleher,
J. K., and Des Rosiers, C. Applications of
Mass Isotopomer Analysis to Nutrition Research. Annual
Review of Nutrition 17: 559-96 (1997).
(ii) Metabolism
of artificial nutrients in animals
R
E L A T E D P U B L I C A T I O N
Desrochers,
S., Quinze, K., Dugas, H., Dubreuil, P., Bomont, C.,
David, F., Agarwal, K. C., Kumar, A., Soloviev, M. V., Powers,
L., Landau, B. R., and Brunengraber, H. R,
S-1,3-Butanediol acetoacetate esters, potential alternates
tolipid emulsions for total parenteral nutrition. J.
Nutr. Biochem. 6: 111-118 (1995).
Leclerc, J., Des Rosiers, C., Montgomery,
J. A., Brunet, J., Ste-Marie, L., Reider, M. W.,Fernandez,
C. A., Powers, L., David, F., and Brunengraber, H. Metabolism
of R- hydroxypentanoate and of -ketopentanoate unconscious
dogs. Am. J. Physiol. 268: E446-E452
(1995).
Desrochers, S., Dubreuil,
P., Brunet, J., Jetté, M., David, F., Landau, B. R.,
and Brunengraber, H. Metabolism of R,S-1,3-butanediol acetoacetate
esters, potential parenteral and enteral nutrients in conscious
pigs. Am. J. Physiol. 268: E660-E667
(1995).
(iii) Potential
of pyruvate esters for the prevention and treatment of
reperfusion injury (myocardial infarction, organ transplant,
hemorragic shock) in animal models (in vivo or isolated
organ perfusions)
I
N A D D I T
I O N
Dr. William C. Stanley, from
the Dept. of Physiology of CWRU,and Dr. Steven Steinberg,
Director of the Dept. of Surgery of Mt. Sinai Medical Center,
are collaborators on this project.
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Paul
Ernsberger, PhD has
post-doctoral trainee or research fellowships available
in his laboratory for the following areas of research: |
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Phospholipids
and polyunsaturated fatty acids, such as arachidonic acid,
are increasingly recognized not only as nutrients, but also
as participants in cellular regulation and signal transduction.
Our laboratory has focused on the role of these nutrient
signaling molecules in the nervous system, particularly in
the regulation of the sympathoadrenal system which is activated
in response to stress, including nutritional stresses such
as weight cycling. Our model system provides an opportunity
for breakthrough research, because we are tracing the signaling
pathways coupled to a novel neurotransmitter receptor which
controls autonomic function. (See following
article)
EDWARDS, L. and ERNSBERGER, P.: The I(1)-imidazoline
receptor in PC12 pheochromocytoma cells reverses NGF-induced
ERK activation and induces MKP-2 phosphatase. Brain
Res.
980: 71-79, 2003. full
text
On the cellular level, the I1-imidazoline receptor couples to phosphatidylcholine
hydrolysis by PC-PLC. Two lipid second messengers, diacylglyceride and arachidonic
acid, are liberated in response to I1-receptor stimulation. The
candidate should have experience in signal transduction assays, immuno precipitation
and blotting, and cell transfection.
Check the following links on IMIDAZOLINE
RECEPTORS:
http://www.med.monash.edu.au/phimr/ireceptor/
http://www.biotrend.com/pdf/imidazrev.pdf
http://www.nyas.org/annals/detail.asp?annalID=770
Please e-mail your CV,
and please include the names and addresses of 3
references to: pre@cwru.edu
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Dr.
Maria Hatzoglou is seeking post-doctoral
fellows with a strong background in molecular biology
and with experience in amino acid transport. |
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Our
laboratory investigates the control of expression of a
gene encoding for a protein with a double function, i.e.,
retroviral receptor and cationic amino acid transporter.
Retro viruses infect their target cells by recognizing
specific cell surface receptor proteins which have an essential
function for the cellular metabolism. The mouse ecotropic
retroviruses infect cells by using as a receptor acationic
amino acid transporter protein (CAT-1). There are two major
areas of focus in our lab:
(i) Regulation
of expression of the gene which encodes for the ecotropic retroviral
receptor:
order to develop more efficient strategies for retrovirus mediated gene transfer
into somatic cells and better understand viral pathogenesis and nutrition.
Transgenic mice expressing the viral receptor in the liver will be used to
study the compatibility of transcription units for tissue specific expression
of the proviral genes in hepatocytes.
(ii) Regulation
of expression of the viral receptor gene focusing on
its function as an amino acid transporter:
The transport of cationic amino acids in mammalian cells is mediated by a family
of cationic amino acid transporters (CATs) which are expressed in a tissue
specific manner. CAT-1 is rather ubiquitously expressed in rat and mouse tissues
except the liver and plays an important role in mediating amino acid transport
and metabolism in different tissues, including arginine homeostasis and erythropoietic
cell development (Genes and development (1997) 11, 914). Furthermore, amino
acid transport is essential for tumor growth. Our goal is to identify the molecular
mechanism of regulation of CAT-1 in healthy and cancer cells. Multiple promoters
and alternative splicing are involved in CAT-1 gene expression (our unpublished
data). We have presently isolated the gene and the promoter flanking region
and we are performing structure/ function studies in response to hormones,
amino acids and growth factors.
R E L A T E D P U B L I C A T I O N S :
Wu
J. Y., Robinson D., Kung H. J., Hatzoglou M. Hormonal
regulation of the gene for the type C ecotropic retrovirus
receptor in rat liver cells. J. Virol. 68:
1615-1623, 1994.
Aulak K. S., Liu J., Wu J., Hyatt S. L., Puppi M., Henning S. J., Hatzoglou
M. Molecular sites of regulation of expression of the rat cationic
amino acid transporter gene. J Biol Chem 271: 29799-29806,
1996.
Hyatt S. L., Aulak K. S., Malandro
M., Kilberg M. S., Hatzoglou M. Adaptive regulation of the cationic
amino acid transporter-1(Cat-1) in Fao cells. J Biol Chem 272:
19951-19957, 1997.
Please
e-mail your CV with the names and addresses of 3
references to:
mxh8@cwru.edu |
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Dr.
Laura E. Nagy has
post-doctoral positions in several projects
which are available in her laboratory.
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Investigate
the effects of diet and ethanol on signal transduction pathways.
(i) To
study the regulation of GLUT4 vesicle trafficking by diet
and ethanol -
We have developed a muscle cell model to investigate the
molecular mechanisms by which lipid and ethanol in the diet
can regulate glucose uptake in muscle by regulating the docking
and fusion of the GLUT4 vesicle with the plasma membrane.
(ii) To study the effects
of ethanol on cytokine production by Kupffer cells -
We have found that ethanol increases the release of tumor necrosis
factor alpha and are investigating the effects of ethanol on the key signal transduction
pathways mediating this response.
(iii) To study the effects of ethanol on protein-protein interactions in
vitro -
Ethanol is known to disrupt signalling via a number of different
signalling cascades. We are interested in understanding the fundamental biochemistry
of these events in order to better predict which signalling cascades are susceptible
to ethanol.
R
E L A T E D P U B L I C A T I O N S :
Nagy, L. E. Molecular
aspects of ethanol metabolism. Ann. Rev. Nutr.,
(in press) 2004.
Kishore, R., McMullen, M.R., Cocuzzi, E., Nagy,
L. E. Stabilization of TNFa mRNA
contributes to increased lipopolysaccharide-stimulated TNFa production
by Kupffer Cells after chronic ethanol feeding. Comparative
Hepatology, 3: S31-S36, 2004. full
text
Rachdaoui, N., Sebastian, R.M.,
Muhlenkamp, P.M., Nagy, L.E. Chronic ethanol
feeding decreases endothelin-1 stimulated glucose uptake in
rat adipocytes: central role for decreased expression of Ga 11. Am.
J. Physiol. 285:
E303-310, 2003. full
text
Rachdaoui, N. and Nagy
L. E. Endothelin-1 stimulated glucose uptake is
desensitized by tumor necrosis factor- a in 3T3-L1 adipocytes. Am.
J. Physiol. 285: E545-551, 2003. full
text
McMullen, M.R., Cocuzzi, E., Hatzoglou,
M. and L.E. Nagy. Chronic ethanol exposure
increases the binding of HuR to TNFa mRNA
AU-rich element in macrophages. J. Biol. Chem. 278:
38333-341, 2003. full text
Nagy, L.E. New
insights into the role of the innate immune response in the
development of alcoholic liver disease. Expt. Biol.
Med. 228: 882-90, 2003. full text |
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