Post Doctoral Fellows in the GCNS

Florence Gizard, Ph.D.
Bruemmer Laboratory

Education:

1997-2002: Ph. D., Physiology and Endocrinology, Laval University Hospital Centre (CHUL), Research Centre in Molecular Endocrinology and Oncology (CREMO), Quebec, Canada
1995-1996: DEA (“Diplome d’etudes approfondies”), Pharmacology and Pharmacochemistry, Louis Pasteur University, Strasbourg, France
1993 - 1995: Magistère, Chemistry and Biology Louis Pasteur University, Strasbourg, France

Current Research:

Current research: Activation and proliferation of vascular smooth muscle cells (VSMC) by cytokines and growth factors secreted in response to injury of the arterial wall play a decisive role for the development of occlusive cardio-vascular disease. VSMC proliferation is mediated by two mechanisms: cell-cycle progression and telomerase activity. Fibrates, which act as activators of nuclear receptor PPARα, are currently administrated alone or in combination with statins to patients with increased cardiovascular risk to impede the progression of atherosclerotic lesions. Whilst we have recently shown that fibrates control G1/S transition of VSMC cell-cycle by targeting the tumor suppressor p16INK4a, we aim now to define whether fibrates also control telomerase activity. If so, we will determine the underlying mechanisms, by notably analyzing whether they act via similar mechanisms than the PPARy ligands thiazolidinediones (TZDs), which have been recently shown in the laboratory to inhibit telomerase activity.

In addition, lipid-loaded macrophages (foam cells) in atherosclerotic lesions are responsible for producing many pro-inflammatory and plaque-destabilizing factors that promote lesion progression. Thus, we analyse the putative regulation and role in macrophages of the telomerase in response to modified low-density lipoproteins and pro-inflammatory factors.

Publications:

Gizard F. Robillard R., Gross B., Barbier O., Revillion F., Peyrat J-P, Torpier G., Hum D.W., Staels B. TReP-132 Is a Novel Progesterone Receptor Coactivator Required for the Inhibition of Breast Cancer Cell Growth and Enhancement of Differentiation by Progesterone. Mol Cell Biol. 2006 Oct;26(20):7632-44.

Nomiyama T., Nakamachi T., Gizard F., Heywood E.B., Jones K.L., Ohkura N., Kawamori R., Conneely O.M., Bruemmer D. The NR4A orphan receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle proliferation. J Biol Chem. 2006 Aug 31

Meisner F., Walcher D., Gizard F., Kapfer X., Huber R., Noak A., Sunder-Plassmann L., Bach H., Haug C., Bachem M., Stojakovic T., Marz W., Hombach V., Koenig W., Staels B., Marx N. Effect of rosiglitazone treatment on plaque inflammation and collagen content in nondiabetic patients: data from a randomized placebo-controlled trial. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):845-50.

Gizard F., Amant C., Barbier O., Bellosta S., Robillard R., Percevault F., Sevestre H., Krimpenfort P., Corsini A., Rochette J., Glineur C., Fruchart J-C., Torpier G., Staels B. PPAR a inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16 INK4a. J Clin Invest. 2005 Nov 1;115(11):3228-3238.

Takashi Nomiyama, MD., PhD
Bruemmer Laboratory

Education:

1995, M.D. Juntendo University Tokyo, Japan Medicine
2002, Ph.D. Juntendo University Graduate School Tokyo, Japan Diabetology

Current Research:

Members of the nuclear hormone receptor superfamily function as key transcriptional regulators of inflammation and proliferation in cardiovascular diseases. In addition to the ligand-dependent peroxisome proliferator-activated receptors and liver X receptors, this family of transcription factors comprises a large number of orphan receptors and their role in vascular diseases remains to be investigated. The neuron-derived orphan receptor-1 (NOR1) belongs to the ligand-independent NR4A subfamily, which has been implicated in cell proliferation, differentiation and apoptosis. I published that PDGF-induced NOR1 transcription in SMC is mediated through CREB-dependent transactivation of the NOR1 promoter and further demonstrate that NOR1 functions as a key transcriptional regulator of SMC proliferation. Now, a lot of further investigations are elucidated.

Publications:

1. Tamura Y, Ogihara T, Uchida T, Ikeda F, Kumashiro N, Nomiyama T, Sato F, Hirose T, Tanaka Y, Mochizuki H, Kawamori R, Watada H. Amelioration of glucose tolerance by hepatic inhibition of nuclear factor kappaB in db/db mice.
Diabetologia. 2006, in press

2. M. Kapoor, T. Nomiyama, D. Bruemmer, F. Kojima, L.J. Crofford. Growth factors and cytokines: Emphasis on their role in wound healing and atherosclerosis. Current Anesthesia & Critical Care (2006) 17, 13-20

3. Nomiyama T, Nakamachi T, Gizard F, Heywood EB, Jones KL, Ohkura N, Kawamori R, Conneely OM, Bruemmer D. The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation. J Biol Chem. 2006 Nov 3;281(44):33467-76.

4. Mita T, Watada H, Ogihara T, Nomiyama T, Ogawa O, Kinoshita J, Shimizu T, Hirose T, Tanaka Y, Kawamori R. Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes. Atherosclerosis, 2006, in press

5. Kapoor M, Nomiyama T, Bruemmer D, Kojima F, Crofford LJ. Growth factors and cytokines: Emphasis on their role in wound healing and atherosclerosis. Current Anesthesia & Critical Care. (2006) 17, 13-20

6. Ogawa D, Nomiyama T, Nakamachi T, Heywood EB, Stone JF, Berger JP, Law RE, Bruemmer D. Activation of Peroxisome Proliferator-Activated Receptor {gamma} Suppresses Telomerase Activity in Vascular Smooth Muscle Cells. Circ Res. 2006 Apr 14;98(7):e50-9.

7. Nishiyama K, Tanaka Y, Nakajima K, Mokubo A, Atsumi Y, Matsuoka K, Watada H, Hirose T, Nomiyama T, Maeda S, Kawamori R. Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study. Diabetologia. 2005 Jul;48(7):1335-8.

8. Takayanagi N, Onuma T, Kato S, Nishiyama K, Nomiyama T, Kawamori R. Association between LDL particle size and postprandial increase of remnant-like particles in Japanese type 2 diabetic patients. Diabetes Res Clin Pract. 2004 Dec;66(3):245-52.

9. Nomiyama T, Igarashi Y, Taka H, Mineki R, Uchida T, Ogihara T, Choi JB, Uchino H, Tanaka Y, Maegawa H, Kashiwagi A, Murayama K, Kawamori R, Watada H, Deterioration of Insulin Stimulated Glucose Uptake by Peroxynitrite is Associated with Tyrosine-nitration of Insulin Receptor Substrate-1. Biochem Biophys Res Commun 2004 Jul 30;320(3):320:639-47

10. Shimo-Nakanishi Y, Hasebe T, Suzuki A, Mochizuki H, Nomiyama T, Tanaka Y, Nagaoka I, Mizuno Y, Urabe T, Functional effects of NAD(P)H oxidase p22phox C242T mutation in human leukocytes and association with thrombotic cerebral infarction. Atherosclerosis 2004;175:109-115

11. Nomiyama T, Tanaka Y, Piao L, Hattori N, Uchino H, Watada H, Kawamori R, Ohta S, Accumulation of Somatic Mutation in mitochondrial DNA and Atherosclerosis in Diabetic Patients. Ann NY Acad Sci. 2004 Apr;1011:193-204

12. Ogihara T, Watada H, Kanno R, Ikeda F, Nomiyama T, Nakao A, German MS, Kojima I, Kawamori R, p38 mitogen-activated protein kinase is involved in activin A- and HGF-mediated expression of pro-endocrine gene neurogenin 3 in AR42J-B13 cells. J Biol Chem. 2003 June 13;278(24);21693-700

13. Takagi M, Tanaka Y, Yamasaki Y, Yamamoto M, Hori M, Nakaniwa T, Niwa M, Uchino H, Tamura Y, Nomiyama T, Watada H, Kawamori R, Responsiveness of insulin-induced cardiac sympathetic nerve activation associates with blood pressure regulation in diabetics. Am J Physiol Endocrinol Metab. 2003 May;284(5):E1022-6

14. Nakajima K, Tanaka Y, Nomiyama T, Ogihara T, Ikeda F, Kanno R, Iwashita N, Sakai K, Watada H, Onuma T, Kawamori R, RANTES Promoter Genotype Is Associated With Diabetic Nephropathy in Type 2 Diabetic Subjects. Diabetes Care. 2003 Mar;26(3):892-8

15. Nomiyama T, Tanaka Y, Piao L, Nagasaka K, Sakai K, Ogihara T, Nakajima K, Watada H, Kawamori R, The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients. J Hum Genet.2003 Mar;48(3):138-41

16. Piao L, Tanaka Y, Nomiyama T, Nakajima K, Ogihara T, Miwa S, Urabe T, Watada H, Kawamori R, Combined Genotypes of ACE and NADPH Oxidase p22phox Associated with Somatic Mutation of mtDNA and Carotid Intima-Media Thickness in Japanese Patients with Type 2 Diabetes Mellitus. Curr Ther Res. 2002 Dec;63(12):842-852

17. Nomiyama T, Tanaka Y, Hattori N, Nishimaki K, Nagasaka K, Kawamori R, Ohta S, Accumulation of somatic mutation in mitochondrial DNA extracted from peripheral blood cells in diabetic patients. Diabetologia. 2002 Nov;45(11):1577-83

18. Nakajima K, Tanaka Y, Nomiyama T, Ogihara T, Piao L, Sakai K, Onuma T, Kawamori R, Chemokine receptor genotype is associated with diabetic nephropathy in Japanese with type 2 diabetes. Diabetes. 2002 Jan;51(1):238-42.

19. Matsunaga H, Tanaka Y, Tanaka M, Gong JS, Zhang J, Nomiyama T, Ogawa O, Ogihara T, Yamada Y, Yagi K, Kawamori R, Antiatherogenic mitochondrial genotype in patients with type 2 diabetes. Diabetes Care. 2001 Mar;24(3):500-3

Awards:

2004 Young Investigator Award of Japan Endocrinology Society

New Investigator Award of 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology

Rodica Petruda Buniciu, Ph.D.
Mao Laboratory

Education:

2005 Ph.D. Nutritional Sciences, University of Kentucky, Lexington, KY
2006 Environmental Systems - Graduate Certificate, University of Kentucky, Lexington, KY
1998 M.S. Molecular Biology; University of Bucharest, Romania
1995 B.S. Biochemistry; University of Bucharest, Romania

Current Research:

Function and regulation of Wnt13 proteins in hematopoietic and endothelial cells: Wnt 13 proteins are members of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. Various members of WNT family function in a variety of developmental processes including regulation of cell growth and differentiation. For many members, involvement in human carcinogenesis as well as in endothelial cell functions was demonstrated. Mao’s lab focuses on the role of Wnt13 and its complex regulation in vascular cells. It was previously established in the laboratory that in addition to alternative promoters and RNA splicing (giving rise to three mRNA isoforms, Wnt13A, Wnt13B and Wnt13C), there is also an alternative translation start in Wnt13B and Wnt13C mRNAs. My work aims at deciphering the regulation of Wnt 13 gene expression at the transcriptional level. In particular, I am studying the regulation of Wnt13 gene expression by survival and apoptotic signals in endothelial cells, as well as differentiating signals in monocytes. I am planning to identify the transcription factors and regulatory elements in Wnt13 promoters responsible for these regulations. The knowledge of the regulation of Wnt13gene expression in the various cells of the vascular wall will be the basis for additional in vivo studies of the expression of Wnt13 in the vascular wall in normal and pathological conditions such as chronic inflammation and atherosclerosis.

Peer-Reviewed Publications:

Glauert HP, Lu Z, Kumar A, Bunaciu RP, Patel S, Tharappel JC, Stemm DN, Lehmler HJ, Lee EY, Robertson LW, Spear BT.Dietary Vitamin E Does Not Inhibit the Promotion of Liver Carcinogenesis by Polychlorinated Biphenyls in Rats. The Journal of Nutrition, 135(2):283-6 (2005)

Marin DE, Taranu I, Bunaciu RP, Pascale F, Tudor DS, Avram N, Sarca M, Cureu I, Criste RD, Suta V, Oswald IP. Changes in performance, blood parameters, humoral and cellular immune responses in weanling piglets exposed to low doses of aflatoxin. Journal of Animal Sciences. 80(5):1250-7 (2002).

Tudor DS, Bunaciu RP. Can Vitamin C Help Fight Aflatoxicosis? Poultry International, 10-14, Vol 40, No 4 (2001).

Shu Liu, Ph.D.
Wang Laboratory

Education:

2000-2005 Peking Union Medical College and China Academy of Medical Sciences,
China, Major Course of Study, Pathology and Path-Physiology

1991-1995 Beijing Medical University, Major Course of Study, Basic Medical Sciences

Current Research:

Cellular proliferation and migration are fundamental processes that contribute to the injury response in major blood vessels. The resultant pathologies are atherosclerosis and restenosis. Diabetic vascular smooth muscle cells exhitbit significantly increased rates of proliferation, adhesion and migration as well as abnormal cell culture morphology. Our previous study showed that type I cGMP dependent protein kinase (PKG I), which are regulated by upstream factor 2 (USF2), played an important role in the diabetic vascular complication. My present research is mainly focusing on identifying the transcription pathway of PKG1 under high glucose stimulation and the therapeutic approaches to regulate it.

Lihua Shi, Ph.D.
Wang Laboratory

Current Research:

The upstream stimulatory family (USF) of transcription factors belongs to the basic helix-loop-helix leucine zipper family of transcription factors characterized by a highly conserved COOH-terminal domain responsible for dimerization and DNA binding. USF2 has been demonstrated to play an important role in regulation of some genes that are closely related to high glucose including TGF-β1 and thrombospondin. We found that the expression of USF2 nuclear protein is increased by high concentrations of glucose in the rat mesangial cells. But we know little about the molecular mechanisms by which USF2 responds to the high glucose. My current and future studies are hoped to provide some new clues about the molecular mechanism from the transcription and posttranslational regulation of USF2 by high glucose.

Ling Tang, Ph.D.
Shao Lab

Education:

B.S., Animal Sciences, Xinjiang Agriculture University, P. R. China
M.S., Animal Nutrition, China Agriculture University, P.R. China
Ph.D., Animal Sciences, Auburn University, Alabama

Current Research:

Obesity is now recognized as a serious, chronic disease. It contributes to the development of type-2 diabetes, specifically in the western countries. Adiponectin (also called AdipoQ, ACRP30, GBP28, and aPM1) is a hormone predominantly expressed from adipose tissue. The circulating levels of adiponectin are decreased in obese individuals and in patients with type 2 diabetes, hypertension and coronary heart diseases.

Adiponectin concentrations in the cord blood or in human infant’s serum are strikingly higher than adults, and newborn serum adiponectin concentrations are positively correlated with body weight. The studies from our laboratory have demonstrated that newborn mice from gestational diabetes mellitus (GDM) mothers have elevated serum adiponectin concentrations, which may contribute to the development of obesity in their later life. The emphasis on my research is in determining the effects of intrauterine GDM exposure on adiponectin expression in fetuses, newborns and adults. The effects of adiponectin on fetal development will also be investigated.

Chenhui Zou, Ph.D.
Shao Lab

Education:

1996 B.S., Shanghai Jiao Tong University, Shanghai, China.
2000 M.S., Chinese Academy of Sciences, Beijing, China.
2005 Ph.D., Peking Union Medical College, Beijing, China.
2006 Post-Doctoral Fellowship, Peking Union Medical College, Beijing, China.

Current Research:

Adiponectin is a hormone produced predominantly by adipocytes and is a regulator of glucose and energy homeostasis. Low plasma adiponectin concentration is associated with a decrease in whole-body insulin sensitivity in humans and has been shown to be predictive of future development of diabetes.

My research interest is in the regulation of adiponectin gene expression and degradation. I am also interested to investigate the intra-organ crosstalk in the context of energy metabolism. Studies are performed in cultured cell or small rodent animal models. The goal of my project is to determine the underlying molecular mechanisms of decreased adiponectin protein levels in obesity and type 2 diabetes.