Pin-Lan Li, M.D., Ph.D.

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Pin-Lan LiProfessor and Vice Chair
Director for Hypertension and Kidney Research
Arthur and Margaret Glasgow Chair

Molecular Medicine Research Building, Room 3050
1220 East Broad Street
Box 980613
Richmond, Virginia 23298-0613
Phone: (804) 828-4793
Fax: (804) 828-2117


  • Yichang Medical College, China, M.D., 1975
  • University of Heidelberg, Germany, Ph.D., 1992

Research interests

  • Cardiovascular pharmacology

Research in my laboratory mainly deals with the cell and molecular regulation of coronary circulation and pathogenesis of renal glomerular injury associated with hyperhomocysteinemia and hypertension. Some specific projects and approaches are as follows:

Transmembrane signaling mechanisms in coronary endothelial cells – lipid rafts and molecular trafficking
Beyond enzyme-mediated amplification in various cell-signaling cascades, we are now exploring another important mechanism that massively amplifies the signals when ligands bind to their receptors. This mechanism is characterized by clustering of membrane lipid microdomains (lipid rafts) and formation of different signaling platforms. In this process, many receptors and signaling molecules aggregate on stimulation, resulting in a very high density of the receptors and other signaling molecules in certain areas of cell membrane to form signaling platforms, which transmit and amplify the signals from receptor activation. A major focus of research is now on defining the mechanism mediating the formation of lipid rafts-associated redox signaling platforms in coronary endothelial cells and exploring the physiological and pathological significance of these redox signaling platforms. Many advanced cell and molecular approaches have been used such as confocal microscopy, fluorescence resonance energy transfer (FRET), electron spin resonance (ESR) spectrometry, high-speed fluorescence imaging, real-time PCR, RNA interference, somatic gene manipulations and genetic engineered animal models.

Novel intracellular second messengers, cadpr in coronary arterial myocytes
Cyclic ADP-ribose (cADPR) serves as a second messenger to mediate intracellular Ca2+ mobilization independent of IP3 signaling pathway in different tissues or cells. Over the past 10 years, we have demonstrated that cADPR induces Ca2+ release from intracellular stores of coronary arterial smooth muscle cells and that inhibition of cADPR production results in the relaxation of coronary arteries. This cADPR-mediated Ca2+ signaling pathway is now considered as an important target in a redox feed-forward regulation in vascular smooth muscle. When vascular smooth muscle cells are activated by different vasoconstrictor stimuli, an NADPH oxidase-associated redox signaling amplification is also initiated. In this process, NADH is used to produce superoxide and NAD+, which could result in cADPR increase since NAD+ is a substrate of ADP-ribosyl cyclase and superoxide can activate this cADPR producing enzyme. cADPR mobilizes intracellular Ca2+, enhancing vasoconstrictor response. Various approaches used in these projects include: high-speed fluorescence imaging of intracellular Ca2+, superoxide and other redox molecules, patch clamp, FRET, video microscopy of small artery functionality, RNA interference, ELISA, ESR, gene overexpression and genetically engineered animal models.

Characteristics and function of a novel lysosomal ca2+ release channel – trp-ml1 in arterial myocytes
Lysosomes are recently demonstrated as an intracellular Ca2+ store where Ca2+ can be mobilized to produce cellular physiological responses. However, little is known about how Ca2+ is released from this store in response to different agonists or stimuli. We have provided the first experimental evidence demonstrating that a Ca2+ release channel is present in lysosomes and that its identity may be mucolopin-1, a transient receptor potential (TRP) channel, namely, TRP mucolipin 1 (TRP-ML1). Given the action of nicotinic acid adenine dinucleotide phosphate (NAADP) stimulating lysosomal Ca2+ release, a hypothesis is that TRP-ML1 may be an NAADP-sensitive Ca2+ release channel in lysosomes of coronary arterial smooth muscle cells. This TRP-ML1 channel may mediate local Ca2+ bursts from lysosomes and leads to a two-phase Ca2+ release that participates in the vasomotor response of coronary arteries to agonists. We are now testing this hypothesis using different physiological, biochemical and molecular approaches, including ion channel reconstitution, lipid bilayer channel recording, patch clamp, high-speed fluorescence imaging, HPLC, ELISA, confocal and electron microscopy, RNA interference, gene mutation and overexpression.

Molecular mechanisms of hyperhomocysteinemia-induced arteriosclerosis and glomerular sclerosis
Hyperhomocysteinemia (hHcys) is a novel risk factor or pathogenic factor for atherosclerosis and glomerular sclerosis associated with hypertension. We are now investigating the molecular mechanisms mediating the pathogenic action of homocysteine (Hcys) in the development of glomerular sclerosis with a major focus on the contribution of guanine nucleotide exchange factors (GEF). The hypothesis to be tested is that the GEF-Vav as a target signaling molecule of Hcys activates Rac-NADPH oxidase and thereby triggers the cascade of glomerular injury and sclerosis including local oxidative stress, podocytes dysfunction, extracellular matrix deposition and fibrosis. A series of cellular, molecular and whole animal experimental approaches are used to test this hypothesis, such as pull-down assay of Rac GTPase, ESR, Western blot analysis, real-time PCR, RNA interference, gene overexpression, dominant active or negative gene mutants, in vivo molecular imaging, isolated glomeruli approaches, HPLC, immunocytochemistry and whole animal monitoring of arterial pressure and renal functions.

Selected publications

Abais JM, Zhang C, Xia M, Liu Q, Gehr T, Boini KM, Li PL. NADPH oxidase-mediated triggering of inflammasomes activation in mouse podocytes and glomeruli during hyperhomocysteinemia. Antioxid Redox Singal. 18(13):1537-1548, 2013. PMCID: PMC3613176.

Li X, Han WQ, Boini KM, Xia M, Zhang Y, Li PL. TRAIL death receptor 4 signaling via lysosome fusion and membrane raft clustering in coronary arterial endothelial cells: evidence from ASM knockout mice. J Mol Med. 91:25-36, 2013. PMCID: PMC3537912

Xu M, Li X, Walsh SW, Zhang Y, Abais JM, Boini KM, Li PL. Intracellular two-phase Ca2+ release and apoptosis controlled by TRP-ML1 channel activity in coronary arterial myocytes.  Am J Physiol-Cell Physiol. 304(5):C458-C466, 2013. PMCID:PMC3602645.

Wei YM, Li X, Xiong J, Abais JM, Xia M, Boini KM, Zhang Y, Li PL. Attenuation by statins of membrane raft-redox signaling in coronary arterial endothelium, J Pharmacol Exp Ther. 345(2):170-179, 2013. PMCID:PMC3629800

Xu M, Li X, Ritter JK, Abais JM, Zhang Y, Li PL. Contribution of NADPH oxidase to membrane CD38 internalization and activation in coronary arterial myocytes. PLoS One 8(8):e71212. 2013 PMCID: PMC3737089

Xu M, Li XX, Xiong J, Xia M, Gulbins E, Zhang Y, Li PL. Regulation of autophagic flux by dynein-mediated autophagosomes trafficking in mouse coronary arterial myocytes. Biochim Biophys Acta –Mol Cell Res. 1833:3228-3226, 2013. PMCID: PMC3855232

Li X, Zhang Y, Xia M, Gulbins E, Boini KM, Li PL. Activation of Nlrp3 inflammasomes enhances macrophage lipid-deposition and migration: Implication of a novel role of inflammasome in atherogenesis. PLoS One. 9(1):e87552, 2014. PMCID: PMC3903678

Zhang Y, Xu M, Xia M, Li X, Boini KM, Wang M, Gulbins E, Ratz PH, Li PL. Defective autophagosome trafficking contributes to impaired autophagic flux in coronary arterial myocytes lacking CD38 gene. Cardiovasc Res. 102(1):68-78, 2014. PMCID: PMC3958620

Xia M, Boini KM, Abais JM, Zhang Y, Li PL. Endothelial NLRP3 inflammasome activation and enhanced neointima formation in mice by adipokine visfatin. Am J Pathol. 184(5):1617-1628, 2014. PMCID: PMC4005976

Abais JM, Xia M, Li G, Gehr T, Boini KM, Li PL. Contribution of endogenously produced reactive oxygen species to the activation of podocyte NLRP3 inflammasomes in hyperhomocysteinemia. Free Radic Biol Med. 16;67C:211-220, 2014. PMCID: PMC3945111

Boini KM, Xia M, Abais JM, Li G, Pitzer AL, Gehr TW, Zhang Y, Li PL. Activation of inflammasomes in podocyte injury of mice on the high fat diet: Effects of ASC gene deletion and silencing. Biochim Biophys Acta. 1843(5):836-45, 2014. PMCID: PMC3986924

Abais JM, Xia M, Li G, Chen Y, Conley SM, Gehr TW, Boini KM, Li PL. Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein during hyperhomocysteinemia. J Biol Chem. 289(39):27159-27168, 2014. PMCID: PMC4175351

Xu M, Li XX, Chen Y, Pitzer AL, Zhang Y, Li PL. Enhancement of dynein-mediated autophagosome trafficking and autophagy maturation by ROS in mouse coronary arterial myocytes. JCMM, 20/14.

Abais JM, Xia M, Zhang Y, Boini KM,  Li PL. Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid Redox Signal. 2014 Oct 20. [Epub ahead of print]

Chen Y, Abais J, Boini K, Zhang Y, Gulbins E, Li PL. Endothelial NLRP3 inflammasome activation associated with lysosomal destabilization during coronary arteritis Biochim Biophys Acta–Mol Basis Dis. doi: 10.1016/j.bbamcr.2014.11.012. [Epub ahead of print]