Lian-Wang Guo, MS, PhD

Portrait of Lian-Wang Guo, MS, PhD
Assistant Professor
Surgery
Address: 
5151 WIMR
1111 Highland Ave
Madison, WI 53705-2275
Telephone: 
(608) 262-6269
Focus Groups: 
Neuroscience/Neuropathology
Signal Transduction
Education: 
PhD, Plant Physiology, Chinese Academy of Sciences
Research Summary: 
Mechanisms of restenosis, proliferation and inflammation, retinal neurodegeneration and regeneration, neural progenitor/stem cells.
Research Detail: 

Treatments for cardiovascular disease, including angioplasty and bypass, frequently fail in large part because of the transition of normal vascular smooth muscle cells to a disease state. We have recently identified a molecular switch, that, when pharmacologically turned off, halts this disease-prone cellular transition. We are conducting in-depth research on this exciting finding, which may someday lead to improved methods for treating recurrent vascular disease.

We are focusing on the bromo and extraterminal (BET) family of proteins, termed epigenetic “readers”. In response to pathogenic stimuli, BET proteins couple with cell type- or cell state-specific transcription factors to activate the expression of a select set of genes which in concert drive cellular transition to a disease state. We are working to differentiate the functions of the various BET proteins and bromo-domains in smooth muscle cell pathogenic transition, and to identify the key transcription factors that are governed by BET proteins. To this end, we are making use of the CRISPR/Cas9 technology for knockout and mutagenesis, and ChIPseq and RNAseq for genome wide analyses.

In parallel, Dr. Guo’s laboratory is exploiting the potential of an endogenous neuroprotective pathway, the Sigma-1 receptor chaperone, in retinal neurons against cell death. We wish our research will produce critical knowledge of effective remedies for blinding retinal diseases, or in a broader sense, neurodegenerative diseases.

For translation, Dr. Guo’s lab is collaborating with bioengineering experts Dr. William Murphy and Dr. Sarah Gong and vascular surgeon Dr. Craig Kent to develop targeted drug delivery platforms.

Selected Publications: 
Shi XD‡, Guo L-W‡*(equal first author, co-corresponding author), Seedial SM‡, Wang B, Takayama T, Franco S, DiRenzo DM, Bo Liu, Kent KC. Local CXCR4 induction in the injured arterial wall contributes to intimal hyperplasia. Stem Cells (2016) In press
Chaudhary MA‡, Guo L-W‡* (equal first author, co-corresponding author), Shi X, Chen G, Gong S, Liu B, Kent KC. Periadventitial drug delivery for the prevention of intimal hyperplasia following open surgery. Journal of Controlled Release 233:174-180 (2016) PMID:27179635
Chu UB, Mavlyutov TA, Yang H, Chu M-L, Schulman A, Mesangeau C, McCurdy CR, Guo L-W* (co-corresponding author), Ruoho AE. The Sigma-2 receptor and progesterone receptor membrane component 1 are different binding sites derived from independent genes. EbioMedicine 2(11):1806-13. (2015). (a new Cell Press/Lancet journal) PMC4740303
Wang B, Zhang M, Takayama T, Shi XD, Roenneburg D, Kent KC, Guo L-W* (Corresponding author). BET bromodomain blockade mitigates intimal hyperplasia in rat carotid arteries. EBioMedicine 2(11):1650-61. (2015). (a new Cell Press/Lancet journal) PMC4740308
Yu X, Takayama T, Goel SA, Shi XD, Zhou Y, Kent KC, Murphy WL, Guo L-W* (Corresponding author). A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia. Journal of Controlled Release 191:47-53 (2014). PMC4156896.
Goel SA‡, Guo L-W‡* (equal first author, corresponding author), Wang B, Song Guo, Drew Roenneburg, Gene Ananiev, F. Michael Hoffmann, K. Craig Kent. High-throughput Screening Identifies Idarubicin as a Preferential Inhibitor of Smooth Muscle versus Endothelial Cell Proliferation. PloS ONE 9:e89349 (2014). PMC3933427.
Guo L-W* (corresponding author), Wang B, Goel SA, Takayama T, Little C, Roenneburg D, Kent KC. Halofuginone stimulates adaptive remodeling and preserves re-endothelialization in balloon-injured rat carotid arteries. Circulation-Cardiovascular Intervention 7(4): 594-601 (2014). PMC4140988.
Shi XD‡, Guo L-W‡*(equal first author, co-corresponding author), Seedial SM‡, Si Y, Wang B, Takayama T, Suwanabol PA, Ghosh, S, DiRenzo D, Liu B, Kent KC. TGF-β/Smad3 inhibit vascular smooth muscle cell apoptosis through an autocrine signaling mechanism involving VEGF-A. Cell Death & Disease (Nature Publishing Group) 5:e1317 (2014). PMC4123076.
Mavlyutov TA, Nickells RW, and Guo L-W* (Corresponding author). Accelerated ganglion cell death in mice deficient in the sigma-1 receptor. Molecular Vision 17:1034-43 (2011). PMC3084245
Song J‡, Guo L-W‡ (equal first author), Muradov H, Artemyev NO, Ruoho AE, Markley JL. Intrinsically disordered -subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure. Proc Natl Acad Sci USA 105:1505-1510 (2008). PMC2234174
Guo L-W* (corresponding author), Muradov H, Hajipour AR, Sievert MK, Artemyev NO, and Ruoho AE. The inhibitory -subunit of the rod cGMP phosphodiesterase binds the catalytic subunits in an extended linear structure. J Biol Chem 281: 15412-15422 (2006). PMID: 16595671
Yu X‡, Takayama T‡, Goel SA, Shi XD, Zhou Y, Kent KC, Murphy WL, Guo L-W** (senior author). A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia. Journal of Controlled Release pii: S0168-3659(14) 00320-4. (2014). PMID: 24852098
Guo L-W‡* (equal first author, corresponding author), Wang B, Goel SA‡, Takayama T, Little C, Roenneburg D, DiRenzo D, Kent KC. Local delivery of halofuginone ameliorates restenosis by inducing adaptive remodeling, reducing intimal hyperplasia, and preserving re-endothelialization. Circulation-Cardiovascular Intervention (2014) In revision
Shi XD‡, Guo L-W‡*(equal first author, corresponding author), Seedial SM‡, Si Y, Wang B, Takayama T, Suwanabol PA, Ghosh, S, DiRenzo D, Liu B, Kent KC. TGF-β/Smad3 inhibit vascular smooth muscle cell apoptosis through an autocrine signaling mechanism involving VEGF-A. Cell Death & Disease (2014) In Press
Goel SA‡, Guo L-W‡* (equal first author, corresponding author), Wang B, Song Guo, Drew Roenneburg, Gene Ananiev, F. Michael Hoffmann, K. Craig Kent. High-throughput Screening Identifies Idarubicin as a Preferential Inhibitor of Smooth Muscle versus Endothelial Cell Proliferation. PloS ONE 9(2):e89349 (2014). PMID: 24586708
Shi XD‡, Chen GJ‡, Guo L-W, Si Y, Zhu M, Pilla S, Liu B, Gong SQ, Kent KC. Periadventitial application of rapamycin-loaded nanoparticles produces sustained inhibition of vascular restenosis. PloS ONE 9(2):e89227 (2014). PMID: 24586612
Shi XD‡, DiRenzo D‡, Guo L-W‡* (equal first author, corresponding author), Franco S, Wang BW, Seedial S, Kent KC*. TGF-β/Smad3 Stimulates Stem Cell/Developmental Gene Expression and Vascular Smooth Muscle Cell De-Differentiation. PloS ONE. 9(4):e 93995 (2014). PMID: 24718260
Goel SA‡, Guo L-W‡* (equal first author, corresponding author), Shi X-D, Kundi R, Sovinsky G, Seedial S, Liu B, Kent KC. Preferential secretion of collagen type 3 versus type 1 from adventitial fibroblasts stimulated by TGF-β/Smad3-treated medial smooth muscle cells. Cellular Signaling. 2012; 25(4):955-960. PMC3595331
Mavlyutov TA, Nickells RW, and Guo L-W** (senior author). Accelerated ganglion cell death in mice deficient in the sigma-1 receptor. Molecular Vision 17:1034-43. (2011). PMC3084245
Chu UB, Song JK, Mavlyutov TA, and Guo L-W** (senior author). GTP-dependent interaction of tubulin with the photoreceptor cGMP phosphodiesterase -Subunit. Neuroscience Letters, 482: 225-229. (2010). PMC2963155
Guo L-W‡ (equal first author), Song J‡, Muradov H, Artemyev NO, Ruoho AE, Markley JL. Intrinsically disordered -subunit of cGMP phosphodiesterase encodes functionally relevant transient secondary and tertiary structure. Proc Natl Acad Sci USA 105:1505-1510. (2008). PMC2234174