CMU scientist determined to find nanoparticles that fight disease
October 13, 2015 12:00 AM
Kathryn Whitehead is an assistant professor of chemical engineering at the Biomolecular Engineering Lab at Carnegie Mellon University in Oakland.
By Sophie Wodzak / Pittsburgh Post-Gazette
Kathryn Whitehead’s affinity for the honey badger, an animal known for its grit and determination, goes back to her days as a postdoc, working in the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. Despite her impressive qualifications, when she began applying to faculty positions, she was met with one rejection letter after another.
“My friend and I were receiving a lot of these letters, so I decided to make a ‘honey badger’ wall, where we’d post every one of them and say, you know what? We don’t care. We’re just going to keep trying,” Ms. Whitehead said. “And it just kind of stuck.”
Now the head of her own laboratory in the chemical engineering department at Carnegie Mellon University, the Allentown, Lehigh County, native continues to be inspired by the critter’s unwavering single-mindedness. She even chose it as her lab’s official mascot.
“People don’t realize it, but so much of science is being told no,” Ms. Whitehead said. “The experiments tell you no, the people funding tell you no, the journals who publish your research say no. I want to say yes.”
That determination has paid off. This year, Ms. Whitehead was named one of Popular Science magazine’s “Brilliant 10,” a list that honors the best and brightest young minds for their contributions in science, technology and engineering.
Ms. Whitehead has been recognized for her innovative work treating diseases that are associated with abnormal protein production.
“We need thousands of protein for life,” she explained. “But often in our genetic code, something can go wrong that affects the way certain proteins are produced. Some diseases, like hemophilia, occur when too few proteins are made, while cancer is the result of too many.”
To fight these diseases, Ms. Whitehead has harnessed the power of small interfering RNAs (siRNAS). As their name suggests, these double-stranded bits of nucleic acid interfere with the production of proteins associated with specific disease, and have the potential to treat everything from genetic disorders to viral infections.
However, getting these drugs where they need to go can be challenging. Protein-based therapies can’t be delivered in pill form, because our bodies simply digest them along with the food we eat. Injection delivers drugs directly into the bloodstream, but they must still bypass the immune system to arrive at a precise location within a designated cell.
Some drugs work very effectively when injected — for example, the insulin used to treat diabetes. But even when injection is successful, it’s still far from ideal. As Ms. Whitehead points out, most patients dislike injecting themselves multiple times a day. When people with diabetes don’t take their insulin, numerous complications can result, which not only affect their health, but also can cost the health care industry billions of dollars in additional care.
“It’s a compliance issue,” she said. “If we could come up with a way of taking these treatments that patients would actually agree to do, great. Everyone wins.”
The newest approach is to put the drugs into a nanoparticle package that can bypass the immune system and safely deliver therapies directly to their targets. To find this perfect vehicle, scientists must first identify which cellular components are necessary to the drug transport process, then use modern chemical techniques to design a delivery system that can overcome or cooperate with those components.
But according to Ms. Whitehead, this is easier said than done. In the past, researchers tried to make educated guesses about which individual nanoparticles would work, tweaking their structures bit by bit in the hopes of arriving at a successful vehicle. But so far, no one has had much luck.
“It’s a perfectly legitimate approach,” Ms. Whitehead said. “But ultimately it seems that you can put in a lot of work with very little result.”
So she decided to take another path. Rather than selecting nanoparticles individually, searching in vain for a proverbial needle in a haystack, Ms. Whitehead created 5,000 different particles, and has spent the past six years testing each and every one of them, trying to see which ones work the best.
“Most people probably see this as being incredibly time-consuming, but I don’t like to think of it that way,” she said. “The pace of the research was quick. I don’t like to mess around.”
By starting with such a large number, Ms. Whitehead and her team were able to come up with some rules that would help them predict which combinations of properties were more likely to be successful, by looking for characteristics that the more successful nanoparticles had in common. Once they had identified 150 of the most promising combinations, they began testing those on mice. Most of those didn’t work, either. But some did.
“I think this approach is often looked down upon by the scientific community as being less intelligent,” Ms. Whitehead said. “But I don’t see it as being less intelligent, I see it as being realistic.”
The winning combinations are now being used to treat several different kinds of diseases that have been selected based upon the knowledge of the disease itself, such as non-Hodgkin’s lymphoma. And so far, the results have been promising.
“We’re finding that these nanoparticles are allowing us to kill cancer cells very effectively, by inducing something called apoptosis, which is when the cancer cells basically commit suicide,” she explained. “It’s very encouraging.”
Moving forward, Whitehead Lab plans to develop drugs that can target cancer cells with specific mutations, ridding the body of disease with fewer harmful side effects. Developing the lock-and-key mechanism necessary for this to work will be its own challenge — but Ms. Whitehead isn’t easily discouraged.
“There are a lot of different ways to go about solving a problem. I like my approach because I think it ultimately will work,” she said. “At the end of the day I’m here because I want to make things that are going to make a difference for people. I’ll do whatever I need to do to make that happen.”
Sophie Wodzak: firstname.lastname@example.org or 412-263-1525.
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