Education

Postdoctoral Fellow
McGovern Medical School at UTHealth, 2012
Postdoctoral Fellow
Baylor College of Medicine, 2009
Ph.D.
Rice University, 2007

Areas of Interests

Research Interests

Membrane mechanics, membrane protein lateral segregation and signal transduction

Research Information

Membrane mechanics, membrane protein lateral segregation and signal transduction

My research focuses on the dynamic spatial communication between nano-assemblies in the cell plasma membrane and signal transduction. Specifically, I study the spatiotemporal organization of Ras proteins anchored to the inner leaflet of the plasma membrane and how changes in the membrane micro-environment alter the structure and dynamics of Ras nanoclusters and consequentially change the activities of the mitogen-activated protein kinases (MAPK) pathway.

The small GTPase Ras proteins regulate cell differentiation, proliferation and survival. Mutation in Ras proteins is one of the most common genetic alterations found in human cancers and is found in ~20% of all mammalian tumors, with particularly high frequency in pancreas (90%), thyroid (55-60%), colon (45%), seminoma (45%) and non-small-cell lung (35%) cancers. Lung and colon cancer are the first and second leading cause of cancer-related death in the US, respectively. Thus, a better understanding of Ras proteins is key to comprehend cancer biology. Ras proteins localize in specialized and spatially distinct nano-assemblies, called nanoclusters, on the inner leaflet of the plasma membrane. These highly dynamic, transient and segregated nano-structures are composed of proteins, lipids and actin cytoskeleton and are absolutely essential for the ability of Ras to bind with downstream effectors and signaling propagation. However, it is still not clear how plasma membrane spatial segregation in the formation of lipid nano-assemblies regulates Ras function. Because of the importance of Ras proteins in cancer biology, it is critical to understand the molecular basis for such essential cellular spatial communication. My research aims to explore the possible mechanisms, such as changes in protein conformations, plasma membrane elasticity, curvature, inter-leaflet coupling, molecular interactions between proteins and their downstream effectors, and interactions between proteins and specific lipids, when exposed to different membrane nanodomains. Additionally, using Ras as a model system, examination of the ability of existing drugs to alter plasma membrane heterogeneity and membrane protein localization and segregation will allow a better understanding of the diverse biological activities of many widely consumed drugs, such as anti-inflammatory drugs, anesthesia and anti-psychotic drugs, etc. Targeting to alter the microenvironment of the plasma membrane is also a new strategy for drug design.

Publications

Publication Information

REFERENCES

  • Prakash P, Sayyed-Ahmad A, Zhou Y, Volk DE, Gorenstein DG, Dial EJ, Lichtenberger LM, and Gorfe AA. (2012) Aggregation Behavior of Ibuprofen, Cholic acid and Dodecylphosphocholine Micelles. Biochimica et Biophysica Acta-Biomembranes 1818 (12): 3040-3047.
  • Zhou Y, Cho K-J, Plowman SJ, and Hancock JF. (2012) Nonsteroidal Anti-inflammatory Drugs Alter the Spatiotemporal Organization of Ras Proteins on the Plasma Membrane. J Bio Chem 287 (20): 16586-16595.
  • Lichtenberger LM, Zhou Y, Jayaraman V, Doyen J, O’Neil RG, Dial EJ, Volk D, Gorenstein D, Boggara M, Krishnamoorti R. (2012) Insight into NSAID-induced Membrane Alterations, Pathogenesis and Therapeutics: Characterization of the Interaction of NSAIDs with Phosphatidylcholine. Biochimica et Biophysica Acta-Molecular & Cell Bio of Lipids 1821 (7): 994-1002.
  • Zhou Y, Plowman SJ, Lichtenberger LM, and Hancock JF. (2010) The Anti-inflammatory Drug Indomethacin Alters Nanoclustering in Synthetic and Cell Plasma Membranes. J Bio Chem. 285 (45): 35188-35195.
  • Zhou Y, Hancock JF, and Lichtenberger LM. (2010) The Nonsteroidal Anti-Inflammatory Drug Indomethacin Induces Heterogeneity in Lipid Membranes: Potential Implication for Its Diverse Biological Action. PLoS ONE 5 (1): e8811.
  • Zhou Y, Dial EJ, Doyen J, and Lichtenberger LM. (2010) Effect of Indomethacin on Bile Acid-Phospholipid Interactions: Implication for Small Intestinal Injury Induced by Nonsteroidal Anti-inflammatory Drugs. Amer J Phys – Gastrointestinal & Liver Physiology G722-G731.
  • Zhou Y, Doyen J, and Lichtenberger LM. (2009) The Role of Membrane Cholesterol in Determining Bile Acid Cytotoxicity and Cytoprotection of Ursodeoxycholic Acid. Biochimica et Biophysica Acta-Biomembranes 1788 (2): 507-513.
  • Zhou Y, Berry C, Storer P, and Raphael RM. (2007) Peroxidation of Polyunsaturated Phosphatidylcholine Lipids during Electroformation. Biomaterials 28 (6):1298–1306.
  • Zhou Y, and Raphael RM. (2007) Solution pH Alters Mechanical and Electrical Properties of Phosphatidylcholine Membranes: Relation between Interfacial Electrostatics, Intramembrane Potential and Membrane Bending Elasticity. Biophys J 92:2451-2462.
  • Lichtenberger LM, Zhou Y, Dial EJ, and Raphael RM. (2006) Nonsteroidal Anti-inflammatory Drug (NSAID) Injury to the Gastrointestinal Tract: Evidence that NSAIDs Interact with Membrane and Extracellular Phospholipids to Weaken the Hydrophobic Surface Barrier and Induce the Formation of Unstable Pores in Membranes. J Pharmacy & Pharmacology 58 (11):1421–1428.
  • Zhou Y, and Raphael RM. (2005) Effect of Salicylate on the Elasticity, Bending Stiffness and Strength of SOPC Membranes. Biophys J, 89:1789-1801.