Gang Bao combines genetic, nano and imaging techniques to fight disease
Gang Bao will bring a host of new expertise to Rice University’s part in the fight against cancer — and many other diseases — when he joins the faculty March 1.
The highly regarded Robert A. Milton Chair in Biomedical Engineering at Georgia Institute of Technology and Emory University is the latest recruit to move to Houston with $6 million in funding from the Cancer Prevention and Research Institute of Texas (CPRIT).
Bao and his colleagues, nine of whom will join him at Rice, cover a wide range of research linked primarily by their interest in the genetic roots of disease and the promise of nanotechnology and biomolecular approaches to treat them.
Among their ongoing projects, lab members are working on targeted genome modification using engineered nucleases, the development of magnetic nanoparticles for use as contrast agents and for ablation of tumors and the application of fluorescent molecular beacons for specific RNA detection in living cells.
“Dr. Bao has an outstanding track record of center leadership in developing and applying nanomedicine for disease diagnosis and treatment, and is a fantastic addition to the Rice effort in translational nanomedicine,” said Michael Deem, chair of the Department of Bioengineering and the John W. Cox Professor of Biochemical and Genetic Engineering.
“His work in the mid-2000s involved groundbreaking contributions to the molecular imaging field, and he has turned to nanomedicine and nanomaterials-based interventions, for example, with special contributions to the isolation of specific cell types from differentiating human pluripotent stem cells. Most recently, Dr. Bao has made major contributions to the use of the CRISPR/Cas9 system for genome editing,” Deem said.
The opportunity to work at Rice’s BioScience Research Collaborative, with its close connections and proximity to the Texas Medical Center, made the offer too good to resist, said Bao, who will be the Foyt Family Professor in the Department of Bioengineering and the CPRIT Senior Scholar in Cancer Research at Rice.
‘The undergraduate programs at Rice are super strong. I always want to attract undergraduates to my lab to do research.’ — Gang Bao
“One thing I really like is that this building is right in the Texas Medical Center, very close to (the University of Texas) MD Anderson (Cancer Center), Texas Children’s (Hospital) and Baylor (College of Medicine),” he said. “For cancer research, this will make it much easier for me to work with colleagues at MD Anderson, a few blocks away, or at Baylor.
“Another attraction, really, is that the undergraduate programs at Rice are super strong. I always want to attract undergraduates to my lab to do research,” he said.
Along with his lab, Bao brings his Nanomedicine Center for Nucleoprotein Machines to Rice. The National Institutes of Health-funded center is developing gene correction techniques to address an estimated 6,000 single-gene disorders. Their first target is sickle cell disease, caused by a single mutation in the beta-globin gene. The mutation causes the body to make sticky, crescent-shaped red blood cells that contain abnormal hemoglobin and can block blood flow in limbs and organs.
Bao calls the tool he and his team created to treat such mutations “nanoscissors,” engineered nucleases that cut DNA strands at a specific site. “We have been working on sickle cell disease since 2008,” he said. “We are testing an idea to take hematopoietic stem cells from a patient’s bone marrow and deliver our nanoscissors into those cells. These nanoscissors generate a cut near the mutation and deliver a correction template that repairs the DNA cut and fixes the mutation. The gene-corrected stem cells will produce normal red blood cells in the patient to replace sickle cells.”
The need is critical because there is no widely available cure for the disease, he said. “In theory, 15 percent of patients could be cured with a bone marrow transplant from a matching donor. In reality, only 5 percent or fewer patients have the opportunity to be cured by this therapy.”
Bao hopes to have the technology ready for human trials in 2018, and if successful, use it to treat other single-gene disorders, including HIV. “There, we’d use nanoscissors to damage the viral genome that integrated into host cells. And there’s potential for this to be used to treat other infectious diseases and cancer,” he said.
Bao and his colleagues are heavily invested in nanotechnology. The lab has developed polymer-coated superparamagnetic iron oxide nanoparticles that can be modified to target tumors and serve as a contrast agent for magnetic resonance imaging in cancer diagnosis. The same nanoparticles can be used to deliver anticancer drug molecules and, under an applied alternating magnetic field, could generate local heat to kill cancer cells. “The synergistic effect of an anticancer drug and hyperthermia could make cancer therapy more effective,” he said.
To reduce side effects, Bao and his team plan to increase the accumulation of drug-carrying magnetic nanoparticles in the tumor by attracting them to tumors, even deep within tissue, by applying a magnetic field. “If the tumor is close to the surface, you can actually mount magnets to the skin as a way to apply the field,” Bao said. “But in deep tissue, that may not work. You might have to put the patient in a large machine to apply the field and generate high nanoparticle accumulation in tumors.” The technology for such deep-tissue targeting “may take another 10 years,” he said.
He said iron oxide nanoparticles might also be embedded in stem cells that could then be directed around the body with magnetic fields.