|Li Li, Ph.D.
1107 Elliman Building
421 E. Canfield Avenue
Detroit, MI 48201
Professor in Department of Internal Medicine, Center for Molecular Medicine and Genetics, and Cardiovascular Research Institute (http://cvri.med.wayne.edu/faculty.php)
Research InterestsWe are studying the molecular mechanisms of smooth muscle phenotypic changes during development and diseases using tissue culture cells and transgenic/knockout mouse disease models. We have been using comprehensive cellular, molecular and genetic approaches to address these issues Understanding the molecular mechanisms of cardiovascular development is critical for developing therapeutic strategies for human vascular diseases including atherosclerosis, aneurysms and Marfan syndrome.
Currently, we have two major projects: (1). characterize the molecular mechanisms of SM22 (aka Transgelin) in smooth muscle cell phenotypic modulation in pathogenesis of vascular injury. We are particularly interested in how changes in TGFbeta signaling, cytoskeletal proteins, transcription factors and epigenetic factors lead to SMC phenotypic changes in the pathogenesis of aneurysm and atherosclerosis. (2). characterize the interplay of regulatory modules for SMC gene expression in different SMC subtypes using BAC transgenesis. We are interested in pursuing the epigenetic changes of regulatory modules in different SMC subtypes.
Another line of research in the lab is to investigate the regulatory mechanisms for a hematopoietic factor Hemogen (aka HEMGN, EDAG), which is specifically expressed in blood islands and active hematopoietic sites during development. Characterizing the function of Hemogen will provide insights on the molecular mechanism of hematopoiesis, leukemogenesis and stem cell differentiation.
We welcome students to join in our lab research projects!
Zhonghui Xu1, Guangdong Ji1, Jianbin Shen, Xiao Wang, Jiliang Zhou and Li Li. SOX9 and Myocardin counteract each other in regulating vascular smooth muscle cell differentiation. Biochem Biophys Res Commun . (2012). 422(2):285-90 PMID: 22580282.
Jianbin Shen; Maozhou Yang; Hong Jiang; Donghong Ju; Jian-Pu Zheng; Zhonghui Xu; Tang-Dong Liao and Li Li. Arterial injury promotes medial chondrogenesis in Sm22 knockout mice Cardiovascular Research (2011) 90:28. PMID: 21183509.
John H Lillvis, Robert Erdman, Charles M Schworer, Alicia Golden, Kimberly Derr, Zoran, Gatalica, Laura A Cox, *Jianbin Shen, Richard S Vander Heide, Guy M Lenk, Leigh Hlavaty, Li Li, James R Elmore, David P Franklin, John L Gray, Robert P Garvin, David J Carey, Wayne D Lancaster, Gerard Tromp, Helena Kuivaniemi Regional expression of HOXA4 along the aorta and its potential role in human abdominal aortic aneurysms. BMC Physiology (2011), May 31;11:9. http://www.biomedcentral.com/1472-6793/11/9 PMID:21627813, PMCID: PMC3125234
Jian-Pu Zheng, Donghong Ju, Hong Jiang, Jianbin Shen, Maozhou Yang, Li Li. Resveratrol induces p53 and suppresses myocardin-mediated vascular smooth muscle cell differentiation. Toxicology Letters, (2010),199:115-122.
Jianbin Shen, Maozhou Yang, Donghong Ju, Hong Jiang, Jian-pu Zheng and Li Li. Disruption of SM22 promotes inflammation after artery injury via Nuclear Factor kB activation. Circulation Research, 2010 106:1351-62.
Jian-Pu Zheng, Donghong Ju, Jianbin Shen, Maozhou Yang, Li Li. Disruption of actin cytoskeleton mediates loss of tensile stress induced early phenotypic modulation of vascular smooth muscle cells in aorta organ culture. Experimental Molecular Pathology 2010 88: 52-57.
Maozhou Yang, Hong Jiang, and Li Li. Sm22α transcription occurs at the early onset of the cardiovascular system and the intron 1 is dispensable for its transcription in smooth muscle cells during mouse development. International Journal of Physiology, Pathophysiology and Pharmacology 2010;2(1):12-19.
Hui Joyce Li, Zaffar Haque, Qing Lu, Li Li, Richard Karas, Michael Mendelsohn. Steroid Receptor Coactivator 3 is a Coactivator for Myocardin, the Regulator of Smooth Muscle Transcription and Differentiation. PNAS 2007 104:4065-70.
Li V. Yang^, Junmei Wan^(co-first author), Yubin Ge,, Zhiyao Fu, Sang Yong Kim, Yuko Fijiwara, Jeffrery W. Taub, Larry H. Matherly, James Eliason and Li Li. The GATA site-dependent Hemogen Promoter Is Transcriptionally Regulated by GATA1 in Hematopoietic and Leukemia Cells. Leukemia. 2006 20:417-25.
Ping Qiu, Raquel P. Ritchie, Xue Qian Gong, Yasuo Hamamori and Li Li. Dynamic changes in chromatin acetylation and the expression of histone acetyltransferases and histone deacetylases regulate the SM22α transcription in response to Smad3-mediated TGFβ1 signaling Biochem Biophys Res Commun. 2006 348:351-358.
Jifeng Zhang, Wei Zhong, Taixing Cui, Maozhou Yang, Xing Hu, Kefeng Xu, Changqing Xie, Changyong Xue, Gary H. Gibbons, Chengyu Liu, Li Li, and Yuqing E. Chen. Generation of an adult smooth muscle cell-targeted Cre recombinase mouse model. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):e23-4.
Ping Qiu^, Raquel Ritchie^(co-first author), Zhiyao Fu, Dongsun Cao, Jerry Cumming, Joseph M. Miano, Da-zhi Wang, Hui J. Li and Li Li. Myocardin enhances Smad3-mediated transforming growth factor-beta1 signaling in a CArG box-independent manner: Smad-binding element is an important cis element for SM22alpha transcription in vivo. Circ Res. 2005 Nov 11;97(10):983-91.
Spears JR, Prcevski P, Xu R, Li L, Brereton G, DiCarli M, Spanta A, Crilly R, Lavine S, vander Heide R. Aqueous oxygen attenuation of reperfusion microvascular ischemia in a canine model of myocardial infarction. ASAIO J. 2003 49:716-20.
Ping Qiu, Xin-Hua Feng, and Li Li. Interaction of Smad3 and SRF-associated complex mediates TGF-beta1 signals to regulate SM22a transcription during myofibroblast differentiation. Journal of Mol. & Cell. Cardiology, 35:1407-1420. 2003.
Li V. Yang, Henry H. Heng, Junmei Wan, Cherie M. Southwood, Alexander Gow, and Li Li. Alternate promoters and polyadenylation regulate tissue-specific expression of Hemogen isoforms during hematopoisis and spermatogenesis. Developmental Dynamics,228: 606-616, 2003.
Rui Xu, Ye-Shih Ho, Raquel P. Ritchie and Li Li. A Human SM22 alpha BAC Encompasses Regulatory Sequences for Expression in Vascular and Visceral Smooth Muscles at Fetal and Adult Stages. Am J Physiol Heart Circ Physiol, 284:H1398-H1407, 2003.
Ping Qiu and Li Li. Histone acetylation and recruitment of serum responsive factor and CREB-binding protein onto SM22 promoter during SM22 gene expression. Circulation Research , May 3;90(8):858-65, 2002. PMID:11988486
Xue Q. Gong, Li Li. Dermo-1, A Multi-Functional Basic Helix-Loop-Helix Protein, Represses Transcription via Interaction with MEF2 and Chromatin Deacetylation. J. Biol. Chem., 277:12300-12307, 2002.
Li V. Yang, Ronda H. Nicholson, Joseph Kaplan, Anne Galy, Li Li. Hemogen is a novel nuclear factor specifically expressed in mouse hematopoietic development and its human homologue EDAG maps to chromosome 9q22, a region containing breakpoints of hematological neoplasms. Mechanisms of Development 104:105-111, 2001.
Li Li, Liu Z, Mercer B, Overbeek P, Olson EN. Evidence for serum response factor-mediated regulatory networks governing SM22alpha transcription in smooth, skeletal, and cardiac muscle cells. Dev Biol. 187:311-21, 1997.
Li Li, Miano JM, Mercer B, Olson EN Expression of the SM22alpha promoter in transgenic mice provides evidence for distinct transcriptional regulatory programs in vascular and visceral smooth muscle cells. J Cell Biol. 132:849-59, 1996.