Dr. Renhao Li, Assistant Professor

structure & function of cell adhesion receptors; molecular mechanism of transmembrane signaling

My lab is interested in the structural basis of transmembrane signaling by cell adhesion receptors.  We focus on the receptors that are critically involved in hemostasis, inflammation and tumor metastasis. 

Structure and function of platelet glycoprotein (GP) Ib-IX-V complex. The interaction between the GP Ib-IX-V complex on the platelet surface and von Willebrand Factor (vWF) that marks the injury site in the artery is widely considered as the first step for hemostasis.  Upon binding to vWF, the GP Ib-IX-V complex transduces into the platelet an activating signal, leading eventually to platelet aggregation and thrombus formation.  Malfunction or lack of the GP Ib-IX-V complex in platelets results in severe bleeding disorders.  The GP Ib-IX-V complex consists of nine subunits of four kinds: Iba, Ibb, IX and V.  Our current focus is to delineate the 3-dimensional organization of the complex, that is, how these subunits interact with one another and assemble into the functional receptor complex.  The insights on the overall organization of the Ib-IX-V complex will help us understand its interaction with vWF and other extracellular and intracellular binding partners, and understand how this complex mediates signals across the plasma membrane to activate the platelet.  Our approach is multidisciplinary, using a combination of cell biological, biochemical, and biophysical techniques.

Regulatory mechanism of ectodomain shedding. Ectodomain shedding is a process in which an integral membrane protein is proteolytically cleaved and its extracellular domain released from the cell.  It affects many membrane proteins including growth factor precursors, amyloid precursor proteins, and proteoglycans.  Excessive shedding activity often leads to diseases such as cancer, arthritis and neurodegenerative diseases.  For several adhesion receptors, the conformation of their cytoplasmic domain or its association with intracellular proteins can affect their shedding activity on the other side of the membrane.  Our focus is to elucidate the structural mechanism underlying such regulation with primarily NMR and fluorescence spectroscopy.

S.-Z. Luo, R. Li. Specific heteromeric association of four transmembrane peptides derived from platelet glycoprotein Ib-IX complex. (in revision).

X. Mo, S.-Z. Luo, A. D. Munday, W. Sun, M. C. Berndt, J. A. López, J.-F. Dong, R. Li. The membrane-proximal inter-subunit disulfide bonds in glycoprotein Ib influence the receptor binding to von Willebrand factor. (in revision).

S.-Z. Luo, X. Mo, J. A. López, R. Li.  Role of the transmembrane domain of glycoprotein IX in the assembly of glycoprotein Ib-IX complex. J. Thromb. Haemost. 5: 2494-2502, 2007.

S.-Z. Luo*, X. Mo*, V. Afshar-Kharghan, S. Srinivasan, J. A. López, R. Li.  Glycoprotein Iba forms disulfide bonds with two glycoprotein Ibb subumits in the resting platelet.  Blood 109: 603-9, 2007.  (Commentary in Blood 109: 393-4)

X. Mo, N. Lu, A. Padilla, J. A. López, R. Li.  The transmembrane domain of glycoprotein Ibb is critical to efficient expression of glycoprotein Ib-IX complex in the plasma membrane. J. Biol. Chem. 281: 23050-9, 2006.

Search PubMed for a complete list of Dr. Li's publications.