Thomas Jefferson University - Nianli Sang
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Nianli Sang
Medicine
Thomas Jefferson University
Jefferson Medical College
Department of Medicine
Division of Hematology/Cardeza Foundation
Assistant Professor
Appointed: 2006
Cell Biology and Signaling Program
Kimmel Cancer Center
Member
Appointed: 2006
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Mailing Address
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1015 Walnut St, Curtis 711
Philadelphia, Pennsylvania 19107
United States
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Qualifications
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Ph.D., Thomas Jefferson University, Genetics, 1997
M.B. (M.D. equivalent in US), Shanghai Medical University (Fudan University Medical School), 1988
Master of Surgery (Residency training), Zhongshan Hospital, Shanghai Medical University, 1992
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Expertise and Research Interests
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One of the most essential requirements for all cells, including tumor cells, to survive is sufficient supply and undisrupted utilization of oxygen and energy resource. Insufficient supply of oxygen (hypoxia) is a common pathological cause in human ischemic disorders including coronary disease and stroke, both are leading causes of death in developed countries. The maintenance of sufficient oxygen and nutrient supply in normal and tumor tissues largely depends on the proper development of vasculature that is primarily composed of endothelial cells and smooth muscles. Under certain conditions such as hypoxia, wound healing and tumor growth, the quiescent cells of vasculature could be stimulated to form new capillaries. The development of vasculature during embryogenesis and the formation of new capillaries in adult under physiological and pathological conditions require HIF, a family of heterodimeric transcriptional factors formed by the dimerization of HIF-alpha and HIF-beta.The function of HIF is controlled largely by the stability and activity of the alph-subunits. A general role of HIF is to regulate the hemastasis of oxygen and to coordinate the glucose metabolism. Particularly, HIF stimulates the production of VEGF and its receptor Flt1 that function in a cooperative manner to promote angiogenesis and neo-vascularization. Moreover, HIF enhances the expression of erythropoietin (EPO), a hormone that stimulates the production of red blood cells to increase the oxygen transportation capacity. Regulation of glucose metabolic pathways by HIF may be required for cells to adapt and tosurvive upon acute hypoxia.Because of the importance of HIF in hypoxia-stimulated angiogenesis, in coordinating the cellular adaptation to low oxygen, and in protecting cells from hypoxia-induced apoptosis, activation of HIF activity is a potential approach for prevention and treatment of coronary insufficiency and other ischemic disorders. On the other hand, blocking HIF activation could be a potential treatment for cancer.
Dr. Sang’s research focuses on better understanding of the molecular mechanisms underlying the hypoxia-inducible factor (HIF)-mediated transactivation. Particularly, Dr. Sang is interested in the dissection of the signal transduction pathways that activate HIF and how these signals change HIF activity. His long-term goal is to design, develop and validate strategies based on the molecular mechanisms of HIF activation to modulate HIF activity in vivo, and eventually explore possible clinical applications of such strategies in cardiovascular diseases and tumors.
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Other Expertise
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Dr. Sang is also interested in the understanding of cell cycle regulation and gene therapy.
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Industrial Relevance
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Research in this laboratory is highly relevant to pharmoceutical industry. Findings from this laboratory can be used to identify potent targets for development of drugs to treat cancer and cardiovascular diseases.
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Keywords
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Angiogenesis; Angiogenesis; Cancer; Cancer; Carcinogenesis; Gene Expression; Gene Expression; Gene Hypoxia
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Publications
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- Liang, D., Kong, X. and Sang, N. Effects of Histone Deacetylase Inhibitors on HIF-1. Cell Cycle, 5(21): in press. 2006
- Fath, D.M., Kong, X., Liang, D., Lin, Z., Chou, A., Jiang, Y., Fang, J., Caro, J. and Sang, N. Histone deacetylase inhibitors repress the transactivation potential of hypoxia inducible factors independently of direct acetylation of HIF-alpha J. Biol. Chem., 281:13612-13619. 2006
- Kong, X., Lin, Z., Liang, D., Fath, D., Sang, N.,* and Caro, J.* Histone-deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of HIF-1alpha. Mol. Cell Biol. 26:2019-2028, 2006 (*co-corresponding author).
- Arnesen, T., Kong, X., Evjenth, R., Gromyko, D., Varhaug, J.E., Lin, Z., Sang, N., Caro, J. and Lillehaug, J.R. Interaction between HIF-1a(ODD) and hARD1 does not induce acetylation and destabilization of HIF-1a. FEBS Lett., 579: 6428-6432. 2005
- Sang, N., Fath, D.M., and Giordano, A. A gene highly expressed in tumor cells encodes novel structure proteins. Oncogene, 23: 9438-9446. 2004
- Severino, A., Baldi, A, Cottone, G., Han, M., Sang, N., Giordano, A., Mileo, A.M., Paggi, M.G., and De Luca, A. Rack1 is a functional target of the E1a oncoprotein. J. Cell. Physiol., 199: 134-139. 2004
- Sang N, Stiehl DP, Bohensky J, Leshchinsky I, Srinivas V, Caro J. MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300. Journal of Biological Chemistry. 278(16): 14013-9, Apr 2003
- Sang N, Fang J, Srinivas V, Leshchinsky I, Caro J. Carboxyl-terminal transactivation activity of hypoxia-inducible factor 1 alpha is governed by a von Hippel-Lindau protein-independent, hydroxylation-regulated association with p300/CBP. Molecular and Cellular Biology. 22(9): 2984-92, May 2002
- Sang N, Caro J, Giordano A. Adenoviral E1A: everlasting tool, versatile applications, continuous contributions and new hypotheses. Frontiers in Bioscience [electronic Resource] : a Journal and Virtual Library. 7: d407-13, Feb 2002
- Minchenko A, Leshchinsky I, Opentanova I, Sang N, Srinivas V, Armstead V, Caro J. Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect. Journal of Biological Chemistry. 277(8): 6183-7, Feb 2002
- Sang N, Severino A, Russo P, Baldi A, Giordano A, Mileo AM, Paggi MG, De Luca A. RACK1 interacts with E1A and rescues E1A-induced yeast growth inhibition and mammalian cell apoptosis. Journal of Biological Chemistry. 276(29): 27026-33, Jul 2001
- Srinivas V, Leshchinsky I, Sang N, King MP, Minchenko A, Caro J. Oxygen sensing and HIF-1 activation does not require an active mitochondrial respiratory chain electron-transfer pathway. Journal of Biological Chemistry. 276(25): 21995-8, Jun 2001
- Martelli AM, Sang N, Borgatti P, Capitani S, Neri LM. Multiple biological responses activated by nuclear protein kinase C. Journal of Cellular Biochemistry. 74(4): 499-521, 1999
- Bals R, Xiao W, Sang N, Weiner DJ, Meegalla RL, Wilson JM. Transduction of well-differentiated airway epithelium by recombinant adeno-associated virus is limited by vector entry. Journal of Virology. 73(7): 6085-8, Jul 1999
- MacLachlan TK, Sang N, De Luca A, Puri PL, Levrero M, Giordano A. Binding of CDK9 to TRAF2. Journal of Cellular Biochemistry. 71(4): 467-78, 1998
- Sang N, Avantaggiati ML, Giordano A. Roles of p300, pocket proteins, and hTBP in E1A-mediated transcriptional regulation and inhibition of p53 transactivation activity. Journal of Cellular Biochemistry. 66(3): 277-85, 1997
- Puri PL, Avantaggiati ML, Balsano C, Sang N, Graessmann A, Giordano A, Levrero M. p300 is required for MyoD-dependent cell cycle arrest and muscle-specific gene transcription. Embo Journal. 16(2): 369-83, 1997
- Sang N, Claudio PP, Fu Y, Horikoshi N, Graeven U, Weinmann R, Giordano A. Transforming region of 243R E1A contains two overlapping but distinct transactivation domains. Dna and Cell Biology. 16(11): 1321-33, Nov 1997
- Sang N, Giordano A. Extreme N terminus of E1A oncoprotein specifically associates with a new set of cellular proteins. Journal of Cellular Physiology. 170(2): 182-91, Feb 1997
- Sang N, Condorelli G, De Luca A, MacLachlan TK, Giordano A. Generation of site-directed mutagenesis by extralong, high-fidelity polymerase chain reaction. Analytical Biochemistry. 233(1): 142-4, 1996
- Bullrich F, MacLachlan TK, Sang N, Druck T, Veronese ML, Allen SL, Chiorazzi N, Koff A, Heubner K, Croce CM. Chromosomal mapping of members of the cdc2 family of protein kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk inhibitor, p27Kip1, to regions involved in human cancer. Cancer Research. 55(6): 1199-205, 1995
- MacLachlan TK, Sang N, Giordano A. Cyclins, cyclin-dependent kinases and cdk inhibitors: implications in cell cycle control and cancer. Critical Reviews in Eukaryotic Gene Expression. 5(2): 127-56, 1995
- Sang, N., Baldi, A., and Giordano, A. The roles of tumor supressors pRb and p53 in cell proliferation and cancer. Molecular and Cellular Differentiation. 3: 1-29., 1995
- Grana X, De Luca A, Sang N, Fu Y, Claudio PP, Rosenblatt J, Morgan DO, Giordano A. PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro. Proceedings of the National Academy of Sciences (USA). 91(9): 3834-8, 1994
- Grana X, Claudio PP, De Luca A, Sang N, Giordano A. PISSLRE, a human novel CDC2-related protein kinase. Oncogene. 9(7): 2097-103, Jul 1994
- Mayol X, Grana X, Baldi A, Sang N, Hu Q, Giordano A. Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain. Oncogene. 8(9): 2561-6, Sep 1993
- Miao T, Wang Z, Sang N, Xiong R, Cao S. Clinical significance of flow cytometric deoxyribonucleic acid measurements of deparaffinized specimens in bladder tumors. European Urology. 21(2): 98-102, 1992
- Miao TJ, Wang Z, Sang N. Correlation between the expression of the P21 ras oncogene product and the biological behavior of bladder tumors. European Urology. 20(4): 307-10, 1991
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Individual Expertise profile of
Nianli Sang, Copyright © Nianli Sang.
Last Updated
by Nianli Sang : Tuesday, October 31, 2006 3:14:49 PM
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