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Outstanding Researcher of the Year
Antibiotics certainly save lives, but long-term and widespread use of the drugs has caused some bacteria to adapt and become harder to kill. The Centers for Disease Control and Prevention (CDC) say that 2 million people become infected with antibiotic resistant bacteria every year in the United States, and at least 23,000 of those people die as a direct result of these infections.
SusanMcDowell, professor of biology and Muncie native, is working on a treatment to make antibiotics and the immune system more effective. McDowell leads a team of Ball State University professors and students, along with researchers from the University of New Mexico’s Center for Molecular Discovery, in this collaborative effort.
“Our main area of interest is in trying to develop new molecules that can combat bacterial infection by mechanisms that are different than those used with antibiotic treatment,” says McDowell.
She and her colleagues just received a patent for a variation of a molecule called ML141. With this molecule, she hopes to develop a drug that eventually can be used alongside antibiotics to help fight infections.
“Antibiotics are not able to access all of the areas of our bodies where bacteria can be hiding out. So specifically, some bacteria are able to actually invade our cells, and when they’re within our cells, most antibiotics are not able to get across the cell membrane or at least not at high enough concentrations to then kill the bacteria inside,” McDowell explains.
She says this often becomes a problem after a person has a knee or hip replacement—the resistant population is able to invade the new device and cause an infection.
“What we’ve been working on for several years now is an approach that blocks the ability of bacteria to invade host cells,” she says. “Then they remain exposed outside of the host cells, and if they are susceptible to antibiotics, then they can get killed off by the antibiotics, or if they’re a resistant population, our own immune system has better access to the bacteria and is able to help clear it away better.”
Statins, staph, and serendipity
Before coming to Ball State in 2003, McDowell was conducting postdoctoral research at Eli Lilly on the cardiovascular effects of statins such as Simvastatin, a prescription drug that helps lower cholesterol. She continued this research at Ball State, but unfortunately, none of her hypotheses were right.
“We had an entire year’s worth of negative data, meaning that every idea that we tried in that grant was wrong. I can laugh now. I was in a panic,” she says with a smile.
A pivotal point in McDowell’s research happened when one of her students, Sharm Knecht, returned to Ball State after conducting a summer internship at IPFW. She had been studying staphylococcus aureus (staph) and asked McDowell for permission to continue her project.
“In all honesty, I kept putting her off because I didn’t know anything about staph. I didn’t know how to grow it,” says McDowell.
Knecht was persistent, and eventually McDowell gave in. “Now in hindsight I’m very grateful for that,” she says.
John McKillip, associate professor of biology, taught McDowell and Knecht how to grow staph. “I made a lot of mistakes. I still make a lot of mistakes. I’m not a microbiologist,” says McDowell.
Meanwhile, McDowell was not making any breakthroughs in her research on statins. One day, in a moment she calls “serendipitous,” she skimmed the literature on statins and staph. She discovered that people who were on statins for lowering cholesterol were at a decreased risk of death due to infection.
“That’s huge. When you’re affecting death rates, then that’s usually important,” she says.
Alongside her students, McDowell set up a simple experiment in the lab in which they pretreated some human cells with Simvastatin. The next day, they infected the cells with staph, and later assessed whether or not there were fewer bacteria in the cells treated with the statin compared to the control cells.
“I remember standing at the incubator that day physically shaking, because I knew if this experiment worked, it was a game changer,” she says. “It was an incredible effect. It was a 90 percent inhibition at a clinical concentration of the statin. So that just opened a whole new direction, and that’s where all of our resources went. To the best of our knowledge, we were the first to discover that statins could limit bacterial infection.”
What’s wrong with statins?
Statins do not kill bacteria like antibiotics do. Rather, statins limit bacteria by immobilizing a host protein called CDC42. “When it’s inactivated, the host cell machinery that the bacteria usually hijack in order to invade us gets turned off. So the bacteria just get frustrated,” says McDowell.
However, statins affect more proteins than just CDC42, and critically ill people can have adverse effects to statins. McDowell began to wonder if another molecule existed that inhibits CDC42 only, without the adverse effects.
After several dead ends and lots of help from her colleagues, McDowell tracked down a CDC42 inhibitor called ML141. This molecule was very unstable; its effects changed from week to week. McDowell began working with Robert Sammelson, chairperson of the Department of Chemistry, who began making alterations to ML141. In October 2015, McDowell and her colleagues received a patent for their altered molecule.
Hope for a clinically available drug
When asked about her hopes for her research, McDowell says, “I dream big. What we would hope is that this drug would be clinically available, so that people who are receiving antibiotics could be put on our compounds at the same time as antibiotics to try to break that infection cycle.”
McDowell hopes that such a compound would prevent infections in people with hip and knee replacements so they would not need additional surgeries. Her drug could also help those who get chronic infections such as strep throat. She says that chronic infections are caused by those pesky bacteria that hide out in cells, so her drug could potentially get rid of those infections for good.
A great job and great students
In the lab and in the classroom, McDowell prepares her students for careers in science. Several current students and graduates shared via email the lasting impact McDowell has made on their lives.
“Without the excellent start that I got working in Dr. McDowell’s lab, I would not be the scientist I am today,” says Robin Dewalt. “Upon graduating in 2011 I left the lab feeling confident and fully prepared to start my new position. To this day, I still hear little reminders and good pointers that she taught in class and also in the lab in my head as I do my work. Her lab gave me a foundation, and luckily for me it was a solid one.”
“I have learned how to work hard and aim high from Dr. McDowell’s example. I also learned more during my time in her lab than I learned in all of my science classes combined. Dr. McDowell has inspired my love of research and teaching,” says Ashley Zahrt who now teaches high school science. “I teach … classes that focus heavily on biomedical science and research. Many of the techniques I teach my students were first taught to me by Dr. McDowell.”
Caroline Hersley is pursuing her Master’s degree in biology and is participating in a co-op with Eli Lilly through Ball State. She says, “Without knowing what Dr. McDowell had taught me and gaining the experience through her lab, I would not be where I am today.”
“I love teaching here. I have the best job,” says McDowell. “I have highly motivated students in each one of my classes. We’re able to do really interesting things in my classes, and I’ve had these great students doing research with me.”
“Every student who’s written to congratulate me on this award, I’ve had to say to them, ‘Please know that you were the one to put the hours in at the bench. I hardly ever run an experiment. It was your work ethic, and your creative ideas.’ Sometimes the students will raise a question that my brain never would have gone to. They get so invested in it. They really have redirected our work many, many, many times. Left up to me, we wouldn’t be where we are today.”
McDowell loves teaching so much that she encourages her students to work at a similar university. “If any of you are thinking about teaching, I would hope that you find a place like Ball State, and I mean that sincerely.”
These accomplishments would not be possible without McDowell’s colleagues Henry Akinbi, Derron Bishop, Heather Bruns, Mark Haynes, John McKillip, VJ Rubenstein, Rob Sammelson, and Larry Sklar, as well as the many hardworking students who have contributed to these efforts.
McDowell extends her gratitude to the following organizations for their financial support of this research: the Ball State Honors College, the College of Sciences and Humanities, the Indiana Academy of Science, the Lilly Foundation, The National Institutes of Health, the National Science Foundation, and Sponsored Projects Administration.