Jian Yang, Ph.D.
 Assistant Professor 

Ph.D., Biochemistry, Ohio State University, Columbus.
Postdoctoral Studies: Molecular Genetics,
University of Texas Southwestern Medical Center at Dallas

 

Research Interest: Regulation of gene expression, Metabolic disorders (diabetes and/or obesity)

 

Our lab is interested in understanding the physiological functions of an important mammalian enzyme, the AMP-activated protein kinase (AMPK), in different organs and tissues. AMPK is a heterotrimeric enzyme complex consisting of a catalytic subunit (a) and two regulatory subunits (ß and g). The a subunit has two isoforms (a1, a2), the ß subunit has two isoforms (ß1, ß2), and the g subunit has three isoforms (g1, g2, and g3). The distinctive physiological functions of these seven different subunits of the AMPK complex are not well understood. AMPK is a key regulator in lipid and glucose metabolism in liver. In the short-term regulation, AMPK phosphorylates and inactivates HMG CoA reductase and acetyl CoA carboxylase (ACC), thus inhibiting both cholesterol and fatty acid synthesis; at the same time, inactivation of ACC decreases malonyl CoA concentration, which in turn derepresses carnitine palmitoyltransferase (CPT1) and activates fatty acid oxidation. The long-term regulation by chronic activation of AMPK in liver is not completely known but was thought to change gene expression. We have generated transgenic mouse models with elevated basal AMPK activity selectively in liver and adipose tissue; in parallel, we are developing cell culture models to study the detailed molecular mechanism by which AMPK regulates gene expression. AMPK is an anti-diabetic drug (e.g., metformin) target and therefore our research will potentially lead to better treatments of obesity, type 2 diabetes, and aging-related diseases. Our research is currently supported by American Heart Association and American Federation For Aging Research.

 

 

Publications

 

1.       Zimmerly, S. Guo, H., Eskes, R., Yang, J., Perlman, P. S. and Lambowitz, A. M. (1995). A group II intron RNA is a catalytic component of a DNA endonuclease.  Cell 83,529-538.

2.       Yang, J., Zimmerly, S. Perlman, P. S. and Lambowitz, A. M. (1996). Efficient integration of an intron RNA into double-stranded DNA by reverse splicing.  Nature 381,332-335.

3.       Eskes, R., Yang, J., Lambowitz, A. M. and Perlman, P. S. (1997). Mobility of yeast mitochondrial group II introns: Engineering a new site specificity and retrohoming via full reverse splicing. Cell 88, 865-874.

4.       Matsuura, M., Saldanha, R., Ma, H., Wank, H., Yang, J., Mohr, G., Scavanagh, S., Dunny, G., Belfort, M. and Lambowitz, A.M. (1997). A bacterial group II intron encoding reverse transcriptase, maturase and DNA endonuclease activities: biochemical demonstration of maturase activities and insertion of new genetic information within the intron. Genes and Dev. 11, 2910-2924.

5.       Yang, J., Mohr, G., Perlman, P. S. and Lambowitz, A.M (1998). The group II intron mobility in yeast mitochondria: Target DNA-primed reverse transcription activity of aI1 and reverse splicing into DNA transposition sites. J. Mol. Biol. 282, 505-523.

6.       Cousinneau, B., Smith, D., Lawrence-Cavanagh, S., Mueller, J.E., Yang, J., Mills, D., Manias, D., Dunny, G., Lambowitz, A. M., and Belfort, M. (1998). Retrohoming of a bacterial Group II intron: Mobility via complete reverse splicing, independent of homologous DNA recombination. Cell 94, 451-462.

7.       Yang, J., Goldstein, J.L., Hammer, R.E., Moon, Y., Brown, M.S. and Horton, J.D. (2001). Decreased lipid synthesis in livers of mice with disrupted site-1 protease gene. Proc. Natl. Acad. Sci. USA. 98, 13607-13612.

8.        Liang, G., Yang, J., Horton, J., Hammer, R.E., Goldstein, J.L. and Brown, M.S. (2002) Diminished hepatic response to fasting/refeeding and Liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. J. Biol. Chem. 277, 9520-9528.

 

Mailing address:
Department of Physiology
Room 3074 Medical Sciences Building
University of South Alabama
College of Medicine
Mobile, Alabama 36688

Phone: 251-460-6814
FAX: 251-460-6386