Research Interest:
In
recent years, the prevalence of obesity-linked type II diabetes
has reached epidemic proportions in developed and developing
countries so that its burden on patients, their families
and the health care system is of growing concern. Although
elevated blood sugar is the hallmark of diabetes, its cardiovascular
complications are likely due to impaired fat metabolism,
which leads to the appearance in blood of fat-rich particles
that are mechanistically linked to cardiovascular and cerebrovascular
diseases that present mainly as heart disease and stroke.
Currently no satisfactory treatments of type II diabetes
that addresses the underlying cause- impaired fat storage.
The broad goal of my laboratory is to identify the underlying
cause of type II diabetes, the molecular mediators that
link obesity to insulin resistance and type II diabetes,
and the cellular sites and signaling pathways that are potential
therapeutic targets.
Mission
Statement:
Although
the laboratory has many cooperative initiatives, each scientist,
independent of level, works on an independent project. Thus,
each scientist helps the other scientists, while having
the primary responsibility of taking a project from a vision
to hypothesis and experimentation, and finally to submission
to and acceptance by a high quality peer reviewed journal.
Scientists are also expected to work as a team and maintain
a collegial atmosphere. To promote the goal of the laboratory,
intellectual and financial resources are provided to each
scientist with the goal of allowing each to be his/her personal
best.
Research
Projects:
Research
in our laboratory is at the interface of medicine and biology,
and is focused on the mechanisms by which type II diabetes
is induced, and the molecular mechanisms of insulin resistance.
The laboratory activities can best be summed by our attempt
to answer relevant medical and scientific questions. These
are as follows. How are adipocyte-secreted factors, especially
inflammatory cytokines, involved in adipocyte gene transcription,
metabolic and secretory function, and insulin sensitivity?
More specifically, how does TNF-alpha induce insulin resistance
in fat cells? What are the candidate drug targets for the
ablation of TNF-alpha pathology?
Future
Plans:
Future studies will continue to focus on identifying the
molecular mechanisms by which TNF-alpha and other inflammatory
cytokines induce insulin resistance. Our long term goal
is to investigate the relevance of our previous findings
in the animal models of obesity and type II diabetes. Such
work would involve adipose-specific transgenic and knockout
mice, which will further test the therapeutic potential
of the targets that we identified.
Another major interest in the lab is to build a detailed
molecular map of signal transduction network in mature adipocytes
as well as in differentiating fat cells. We use a wide variety
of techniques, including functional genomics, real-time
quantitative PCR, gene chip microarray, and proteomics.
The unifying theme that ties all our experiments together
is the interest to identify the molecular mechanisms driving
the development of insulin resistance, and to contribute
to the development of an effective therapy for type II diabetes.
Publications:
1. Ruan, H.
and Pownall, H. J.: Overexpression of 1-acyl-glycerol-3-phosphate
acyltransferase-alpha enhances lipid storage in cellular
models of adipose tissue and skeletal muscle. Diabetes
50 (2): 233-240. 2001
2. Ruan, H.,
Hacohen, N., Golub, T. R., Van Parijs, L., and Lodish, H.
F.: Tumor necrosis factor-α suppresses adipocyte-specific
genes and activates expression of preadipocyte genes in
3T3-L1 adipocytes: nuclear factor-B activation by
TNF- is obligatory. Diabetes 51 (5):
1319-1336. 2002.
3. Ruan, H.,
Miles, P. D. G., Ladd, K. Ross, C. M., Golub, T. R., Olefsky,
J. M., and Lodish, H. F.: Profiling gene transcription in
vivo reveals adipose tissue as an immediate target of tumor
necrosis factor-α: implications for insulin resistance.
Diabetes 51 (11): 3176-3188. 2002.
4. Ruan, H.,
Pownall, H. J., and Lodish, H. F.: Troglitazone antagonizes
TNF--induced reprogramming of adipocyte gene expression
by inhibiting the transcriptional regulatory functions of
NF-κB. Journal of Biological Chemistry 278 (30):
28181-28192. 2003
5. Ruan, H.
and Lodish, H. F.: Insulin resistance in adipose tissue:
direct and indirect effects of tumor necrosis factor-α.
Cytokine and Growth Factor Review 14 (5):
447-455. 2003
6. Ruan, H.,
Zarnowski, M., Cushman, S., and Lodish, H. F.: Standard
isolation of primary adipose cells from mouse epididymal
fat pads induces inflammatory mediators and down-regulates
adipocyte-genes. Journal of Biological Chemistry 278
(48): 47585-47593. 2003.
7. Ruan, H.
and Lodish, H. F. : Regulation of Insulin Sensitivity by
Adipose Tissue-Derived Hormones and Inflammatory Cytokines.
Invited Review. Current Opinion in Lipidology 15 (3):
297-302. 2004
8. Ruan, H.
and Lodish, H. F.: Dyslipidemia and Atherosclerosis: Mechanism,
Transcriptional Regulation, Consequences, and Treatment.
Invited Review. Lipid Disorder Updates. Issue
of June, 2004.
9. Rozo, A. V.,
Vijayvargia, R., Weiss, H. R., Ruan, H. Silencing
Jnk1 and Jnk2 accelerates basal lipolysis and promotes fatty
acid re-esterification in mouse adipocytes. Diabetologia,
2008. In Press.
Laboratory
Staff:
Padma
Narayanan (Research Teaching Specialist IV)
Andrea V. Rozo
(Graduate Student)
Lab Phone: 732-235-4037
Contact Information:
Hong Ruan, M.D.,
Ph.D.
Assistant Professor
Physiology and Biophysics Room 514
Robert Wood Johnson Medical School-UMDNJ
675 Hoes Lane Piscataway,
NJ 08854
Phone: 732-235-5552
Email: ruanho@umdnj.edu
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