Kirk Hou, an MD/PhD student at the School of Medicine, has discovered an innovative way to manipulate proteins in cells — a method that potentially could be used to treat cancer, heart disease and arthritis.
Proteins are the workhorses of a cell. They carry out the instructions encoded in the DNA. Some diseases result from an overproduction of proteins, while others develop when too little of a key protein is made.
Hou, who is planning to specialize in ophthalmology, is fascinated by that process — so much so, he developed a way to decrease the amount of certain proteins a cell can make.
His discovery, which he licensed through the university’s Office of Technology Management, is the basis for a St. Louis startup company.
Although Hou earned his doctorate in computational and molecular biophysics, his research was conducted in a cardiology lab. His work spans pharmacology, biomedical engineering and cellular biology.
“My research would not have been possible without collaborators from across the Medical Campus,” Hou said. “The multidisciplinary approach required to do this sort of work is unique to the environment at Washington University.”
Hou’s PhD research was focused on devising a method to deliver siRNA into cells. Small interfering RNA, or siRNA, can stop cells from making specific proteins. But cells are very good at blocking siRNA before it can do its job. Hou developed a strategy to sneak siRNA into cells by creating a nanoparticle — think Trojan horse — derived from melittin, a peptide found in bee venom.
Although other scientists have had some success delivering siRNA into certain tissues’ cells, Hou’s method appears to work across a variety of cell types with improved safety and efficiency.
In the laboratory of his mentor and principal investigator, Samuel Wickline, MD, Hou initially tested his nanoparticle in melanoma cells; adult T cell leukemia/lymphoma cells; endothelial cells, which line blood vessels and are damaged in heart disease; and immune cells involved in atherosclerosis, or hardening of the arteries.
Hou’s nanoparticles also were tested in mouse models of rheumatoid arthritis, in collaboration with the School of Medicine’s Christine Pham, MD. His strategy effectively halted the typical progression of inflammation and joint destruction in this painful condition. Other collaborators now are testing Hou’s method in mice to treat adult T cell leukemia/lymphoma and acute kidney injury caused by low blood flow. If successful, the same technology potentially could be evaluated in people.
The startup that licensed Hou’s technology hoped to retain him as an employee, but he decided to complete his residency training in ophthalmology first. On Match Day, he learned he will complete a preliminary year in internal medicine at Barnes-Jewish Hospital, after which he will go to University of California, Los Angeles, to train in ophthalmology.
Hou believes that direct contact with patients will best inspire his future research.
“Ideally, I will be developing new treatments for eye disease in the next 10 to 15 years,” he said.