Research Themes:
Instrumentation, Imaging and Image-Guided Therapy
Molecular and Cellular Engineering

Education

Postdoctoral Training, Emory Univ. & Georgia Tech, 2005
PhD, Indiana University, Bloomington, 2004
BS, Nankai University, China, 1998

Research Interests

• Nanomedicine/Nanotechnology
• Molecular engineering
• Molecular imaging
• Targeted drug delivery

Contact Information

Department of Bioengineering
University of Washington
Box 355061
William H. Foege Building, Room N530M
Phone: 206-543-6562
E-mail
Web site: http://faculty.washington.edu/xgao/

Research Description

The Gao research group is interested in nanomedicine, which is the use of engineered nanostructures for detection, analysis and treatment of human diseases such as cancer, cardiovascular diseases, infectious diseases and neurological diseases.

Nano Toolbox: Nanotechnology has recently received broad interest from biomedical researchers and may change the very foundations of disease diagnosis, treatment and prevention. For example, advances in semiconductor quantum dots (Qdots) has produced a new class of fluorescent labels for ultrasensitive and multiplexed molecular imaging. These quantum-confined nanoparticles provide unique optical and structural properties that are not available from traditional single molecules or bulk solids. Valuable Qdot properties include size tunable emission spectrum, large absorption coefficient, narrow emission peak, broad absorption profile, photostability, and very high brightness. Recently, we have made a breakthrough in development of highly biocompatible nanoparticle-polymer hybrid structures using molecular self assembly. This breakthrough opened new opportunities for molecular imaging in living cells and animals. Due to their narrow and Gaussian-shaped emission peaks, Qdots are well suited for multiplexing applications, especially in conjunction with spectral imaging setup, which can resolve multiple Qdot emission peaks with spectral separations as small as 5 nm. This unprecedented multiplexing capability will allow simultaneous examination of many critical proteins and genes and provide better understanding of the molecular regulatory and signaling networks related to cancer prognosis. We are currently developing new synthetic chemistry, surface functionalization and bioconjugation techniques for applications in imaging, detection and drug delivery. Besides Qdots, we are also interested in other types of nanoparticles such as magnetic nanoparticles, metallic nanoparticles and polymeric nanoparticles. For example, iron oxide-based magnetic nanoparticles are the ideal material for translational research and clinical studies. Several types of iron oxide nanoparticles are currently used as MR contrast agents in clinical trials. These nanoparticles are synthesized in water using dextran as a surface coating and stabilizer, which results in large particle size (due to the dextran shell), wide size distribution and low magnetic induction. To improve the quality and potency of the magnetic probe, we are currently exploring a high temperature oil phase synthesis that has become possible only recently. The resultant nanoparticles are highly uniform in size, and have single magnetic domains, tunable chemical composition, and no bulky dextran coating layers. Primary applications would be in MR imaging and drug delivery.

Multiplexed Biomolecule Screening: Based on the novel optical properties of Qdots and on our abilities to incorporate them into microbeads at precisely controlled ratios, we have developed an optical barcoding technology for massive parallel and high-throughput analysis of biological molecules. This nano-barcoding approach can produce millions of distinct optical codes for simultaneous analysis of genes, proteins and cells. To further improve the detection sensitivity and throughput, we will have the bead matrix reloaded with multifunctional nanoparticles.

Molecular Diagnostics: It is well known that cancer varies both genetically and phenotypically between patients who may have the identical type and stage of cancer. Each person's cancer is as unique as his or her fingerprint, which explains unpredictable responses to therapies and poses new biotechnology challenges for tumor characterization on the molecular level. For example, some prostate cancer types are androgen dependent, and can be treated with androgen deprivation therapy; others are androgen independent. In another example, approximately 30% of breast cancer patients respond to Herceptin treatment well, due to overexpression of Her-2 receptors, while the majority do not. We are currently exploring the use of multicolor Qdots for in situ quantitative profiling of tumor markers. In correlation with pathology, the results are expected to have major impact on accurate tumor characterization and differentiation and on molecular therapeutics.

In vivo Molecular Imaging: Rapid advances in non-invasive imaging are changing the way we visualize molecular dynamics in living organisms. The high sensitivity of nanoparticle-labeled cells allows detection down to the single-cell level. Under in vivo conditions, nanoparticle probes can be delivered to tumors by both passive and active targeting mechanisms. In the passive mode, macromolecules and nanometer-sized particles are accumulated preferentially at tumor sites through an enhanced permeability and retention (EPR) effect. For active tumor targeting, nanoparticles are guided to the tumor site by biomolecular ligands, such as antibodies, peptides and small molecule antagonists.

Targeted and Traceable Drug Delivery: We are interested in inorganic nanoparticle-organic polymer hybrid structures for targeted and traceable drug delivery. The nanoparticles have dual functionalities, serving as both contrast agent and structural scaffold. Hydrophobic cancer drugs can be trapped between the core particle and polymer surface coating layer, whereas hydrophilic therapeutic agents such as siRNA can be adsorbed on the nanoparticle surface.

Teaching Activities

• BIOEN 303: Bioengineering Signal Processing
• BIOEN 499: Bioengineering and Nanotechnology
• BIOEN 599: Bionanotechnology

Professional Experience

• 2005-present: Assistant Professor, Department of Bioengineering, University of Washington, Seattle
• 2004-2005: Postdoctoral Research Associate, Winship Cancer Institute at Emory University and the Wallace Coulter Department of Biomedical Engineering at Georgia Tech.
• 1999-2004: Graduate Research Assistant, Department of Chemistry, Indiana University, Bloomington.
• 1994-1998: Undergraduate student, Department of Chemistry, Nankai University, Tianjin, China.

Selected Publications

• Lifeng Qi, and Xiaohu Gao, "Quantum Dot-Amphipol Nanocomplex for Intracellular Delivery and Real-Time Imaging of siRNA," ACS Nano, 2008, 2, 1403-1010.
• Maksym Yezhelyev, Lifeng Qi, Ruth M. O’Regan, Shuming Nie, and Xiaohu Gao, "Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging," Journal of the American Chemical Society, 2008, 130, 9006-9012.
• Jian Yang, Shivang R. Dave, and Xiaohu Gao, "Quantum dot nanobarcodes: epitaxial assembly of nanoparticle-polymer complexes in homogeneous solution," Journal of the American Chemical Society, 2008, 130, 5286-5292
• Xiaohu Gao, Yuanyuan Cui, Richard Levenson, Leland Chung, and Shuming Nie, “In vivo cancer targeting and imaging with semiconductor quantum dots,” Nature Biotechnology 2004, 22, 969-976. (issue cover)
• Mingyong Han, Xiaohu Gao, Jack Su, and Shuming Nie, “Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules,” Nature Biotechnology 2001, 19, 631-635. (issue cover)