Research Interests

We are studying the molecular mechanisms of smooth muscle phenotypic changes during development and diseases using tissue culture cells and transgenic/knockout mouse models. We are particularly interested in the transcriptional regulation and epigenetic regulation of smooth muscle gene expression in response to injury signals. 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.

Currently, we have two major projects: (1). characterize the molecular mechanisms of smooth muscle phenotypic changes in response to the vascular injury (carotid artery denudation and aneurysms). We are particularly interested in how changes in TGFbeta signaling, cytoskeletal proteins, transcription factors and epigenetic factors lead to SMC phenotypic changes in mouse models. (2). characterize the interplay of regulatory modules for SMC gene expression in different SMC subtypes using BAC transgenesis. We are interested in pursing the epigenetic changes of regulatory modules in different SMC subtypes.

Another line of research in the lab is to characterize a novel nuclear factor Hemogen, which is specifically expressed in active hematopoietic sites and marks the development of hematopoiesis. Characterizing the function of hemogen will provide insights on the molecular mechanism of hematopoietic development and differentiation.

Selected Publications

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.

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.

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.

Ping Qiu and Li Li. Chromatin acetylation by coactivators is involved in SRF-mediated activation of SM22 gene. Circulation Research, 90:858-865, 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.

Priscilla S. Chang, Li Li, John McAnally, and Eric N. Olson. Muscle Specificity Encoded by Specific Serum Response Factor-binding Sites. J. Biol. Chem., 276:17206-17212, 2001.

S. Paul Oh, Tsugio Seki, Kendrick A. Goss, Takeshi Imamura, Youngsuk Yi, Patricia K. Donahoe, Li Li, Kohei Miyazono, Peter ten Dijke, Seongjin Kim, and En Li. Activin receptor-like kinase 1 modulates transforming growth factor-1 signaling in the regulation of angiogenesis. PNAS 97:2626-2631, 2000.

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