Dr. Maria Hatzoglou is seeking doctoral candidates with an orientation in molecular biology.
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:
(1)
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.
(2) 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are involved in CAT-1 gene expression (our unpublished data).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.
Applications
are available from the School
of Graduate Studies' website
Dr. Paul E. Ernsberger has graduate fellowships available in his laboratory for the following areas of research:
(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:
R
E L A T E D P U B L I C A T I O N S :
|
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). |
(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 S :
|
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. |
- Dr. Henri Brunengraber is seeking Ph.D. candidates to work on the research projects briefly outlined below:
NUTRITIONAL
BIOCHEMISTRY/METABOLISM
& MOLECULAR NUTRITION
Cycles
of weight loss and regain increase the risk of heart disease in human
populations. Our laboratory studies show that rapid regain of weight
after a low calorie diet increases blood pressure, and has harmful effects
(see American Journal of Physiology 270:R864-72, 1996).
High levels of stress hormones seem to be the culprit in the hazards
of weight cycling. The student will carry out studies designed to unravel
the hormonal and cellular basis for the effects of weight cycling, and
test the effects of different diets during the weight loss and relapse
phases. The fellowship program is available to students with biology
and chemistry training.
Please e-mail curriculum-vitae, and the name and addresses
of 3 references to: pre@po.cwru.edu
