Research Interests

The main research interest in my laboratory is to understand the regulatory network that controls smooth muscle cells (SMC) gene expression during cardiovascular development and cardiovascular diseases. To address these questions, we have been using a smooth muscle gene, SM22, as a model to characterize the interaction of cis-acting regulatory elements and transcription factors in both tissue culture cells and in transgenic mice. We have shown that the SM22 promoter is only expressed in arterial not venous nor visceral SMCs, in spite of the fact that the endogenous SM22 gene is expressed in all types of SMCs. These findings, for the first time, revealed that different subtypes of SMCs use distinct regulatory mechanisms to control gene expression. Extensive studies have established the combinatory interaction of SRF with other transcription factors and cofactors in regulating SMC gene expression. We also established the critical roles of chromatin modification in regulating SMC gene expression. Currently, we are investigating the molecular basis of the regulatory network that controls the SM22 expression in different SMC subtypes.

TGF-beta signals are known to be critical for vascular development and the pathogenesis of vascular diseases. Our recent discovery of the direct interaction of SRF and Smad3 furthers our understanding of the molecular mechanisms that mediate TGF-beta signal transduction. Furthermore, we have identified a Smad3 binding site in the SM22 promoter that is critical for its transcriptional control. Currently, we are investigating how Smad proteins participate in the SRF-mediated regulatory network in vitro and in the context of chromatin. Understanding these molecular mechanisms will provide important insights into designing new therapeutic strategies for vascular diseases.

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. Interestingly, the human homolog EDAG is mapped to chromosome 9q22, a leukemia breakpoint. Like Hemogen, EDAG exhibited restricted expression in hematopoietic tissues and cells. We have accumulated extensive results that suggest Hemogen and its human homologous gene EDAG may play roles in hematopoietic development and neoplasms. Characterizing the function of hemogen will provide insights on the molecular mechanism of hematopoietic development and differentiation.

Selected Publications

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.

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.

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.

J. Richard Spears, Cassandra Henney, Petar Prcevski, Rui Xu, Li Li, Giles Brereton, Marcello DiCarli, Ali Spanta,Richard Crilly, Steven Lavine, Richard Vander Heide. Aqueous Oxygen Hyperbaric Reperfusion in a Porcine Model of Myocardial Infarction. J Invasive Cardiol. 14(4):160-166, 2002.

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.

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.

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.

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.