MD/PhD Students Engage in Pioneering Research

MD/PhD Students Engage in Pioneering Research

Topics include healthy fats that help failing hearts and the impact of aerobic exercise on addiction

By: Susan Reich

Martina Mustroph, a student in the Medical Scholars Program at the College of Medicine's Urbana campus, has researched whether aerobic exercise could help drug addicts withstand temptation.

College of Medicine MD/PhD student Ryan Lahey was psyched. Time magazine had just published a story based on his research group’s article in the American Heart Association journal Circulation about a groundbreaking study on the effects of oleate, the kind of fat found in olive oil, on rats with heart failure.

A bout 140 miles south of Chicago, at the College of Medicine’s Urbana campus, MD/PhD student Martina Mustroph had been pursuing groundbreaking research of her own with a study that could have far-reaching implications in the field of substance abuse and addiction treatment.

Although Lahey and Mustroph are pursuing different paths to discovery and innovation, they are both reaping the benefits of the College of Medicine’s MD/PhD programs: the Medical Scientist Training Program in Chicago and its counterpart in Urbana, the Medical Scholars Program.

The College of Medicine trains a diverse corps of exceptionally bright and talented students for distinguished careers in academic medicine and research. The NIH-funded MSTP in Chicago has grown rapidly, and now admits 10 students yearly. The MSP has thrived as a unique collaboration with the University of Illinois at Urbana Champaign—MSP students receive PhDs (or occasionally other degrees) from UIUC graduate programs.

“It is an extraordinary era for those with a commitment to medicine and a passion for science,” says MSTP director and senior associate dean for research Larry S. Tobacman, MD. “Accelerating advances across many scientific disciplines, exemplified by the completion of the human genome sequence, will dramatically affect the practice of medicine in the coming decades. In biological discovery, and in the application of discovery to the care of patients, those with combined training as physicians and scientists will be leaders.”

MD /PhD training is a unique and demanding path involving approximately eight years of rigorous training and study, regarded by those who traverse it as more of a calling than a career choice. It’s also a program that weeds out all but the most accomplished and highly motivated students — admitting only a handful out of the hundreds who apply each year.

But for those who have the academic chops, the stamina and the self-discipline to complete an MD/PhD program, the rewards are abundant. According to the Association of American Medical Colleges, “There are few comparable careers that allow one to experience the passion of solving a patient’s medical struggles while pursuing research that may define the mechanism of the patient’s disease and may ultimately translate into a clinical cure for that disease.”

That opportunity to follow a disease from bench to bedside while advancing medicine through research and education is the Holy Grail for many MD/ PhD students — including Ryan Lahey.

“I enrolled in this program because I wanted to think creatively about diseases,” says the 30-year-old Downers Grove native, who will graduate from the Medical Scientist Training Program in 2016. “I was drawn to UIC because of its commitment to providing exceptional healthcare for all, as well as the opportunity to work with world-class investigators in biomedical research. I think research is where you get a lot of bang for your buck in terms of helping a lot of people at once by moving the field forward.

“But I also think there’s something very gratifying about being a human presence next to the bed and helping people one at a time as a clinician,” he adds. “Seeing the human side of medicine — and taking that into the lab with you — is a really good way to inform the research. It’s important to have the whole clinical perspective.”

Led by his mentor, Center for Cardiovascular Research director E. Douglas Lewandowski, PhD, Lahey’s research examines cardiovascular physiology and biochemistry through nuclear magnetic resonance spectroscopy and imaging, along with metabolic regulation by enzyme activity and expression in intact tissues.

Lahey’s heart failure study compared two different types of oil—palmitate and oleate. When Lahey and his fellow researchers in Lewandowski’s cardiac research lab administered palmitate to the failing rat hearts, the hearts remained unchanged, with impaired fat metabolism and storage. But when they treated the failing hearts with oleate, the hearts began functioning like healthy hearts, with improved contraction and normal fat metabolism.

More research needs to be done, including clinical trials with human subjects, but the study results—which may explain why the Mediterranean diet, with its emphasis on olive oil, is so heart-healthy—could eventually lead to therapeutic dietary regimens for patients with heart failure. Lahey, the lead author of the paper published in the AHA journal, was thrilled to see the groundbreaking work in Lewandowski’s cardiac lab garnering national attention.

The German-born Mustroph, who majored in psychology with a concentration in neuroscience as an undergrad, had similar goals when she entered the Medical Scholars Program, which is directed by James M. Slauch, PhD.

Martina Mustroph, a student in the Medical Scholars Program at the College of Medicine's Urbana campus, has researched whether aerobic exercise could help drug addicts withstand temptation.“By my senior year in college, I had become very interested in the biological basis of behavior,” she recalls. “I was doing drug research in an animal behavior lab, and I fell in love with the research process. I had planned to go to medical school, but I was torn. I began to wonder if I should pursue graduate studies in neuroscience instead.

“My undergraduate advisor pointed out that I could do both through an MD/PhD program,” she adds. “I felt that the Medical Scholars Program in Urbana would give me the necessary training in neuroscience and the medical knowledge and skills I needed to take this path.”

Her study involved a phenomenon called “conditioned place preference,” which refers to the tendency for mice to show a marked preference for a location where they had received liquid cocaine — in much the same way that recovering drug addicts and alcoholics can experience strong cravings when they revisit the places where they once indulged.

Mustroph and her research team worked in the Rhodes Lab in the University’s Beckman Institute for Advanced Science and Technology, a world-class, interdisciplinary facility devoted to groundbreaking research in the physical sciences, computation, engineering, biology, behavior, cognition and neuroscience. The team tracked the effect of aerobic exercise on the ability of the mice to disassociate the memory of a particular setting with cocaine.

In 2011, Mustroph reported in the European Journal of Neuroscience that the running mice learned that a particular chamber of a cage was no longer associated with cocaine more quickly than the control group of sedentary mice. Mustroph then embarked on a related study to determine whether being in motion helped the mice learn not to associate the environment with cocaine, or if exercise somehow interfered with the long-term consolidation of the initial association.

If the rodent results from this research can be replicated in human trials, these studies may pave the way for a new type of therapy for substance abusers who have learned to associate certain people, places and things with their drinking and drug use.

Lahey and Mustroph both say their collaborative endeavors have broadened their perspectives and advanced their research.

“I’ve been able to collaborate with one of the leading chemistry labs studying neuropeptides in the country to look for novel and known neuropeptide targets in the brains of mice,” says Mustroph. “Because I’m not trained as a chemist, this required extensive training in mass spectrometry techniques, which the lab provided. This has broadened the scope of my neuroscience experiments, which were largely behavioral before my collaboration with the chemistry group, and has enabled me to look for molecular targets for the behavioral effects that I’m seeing in my studies. I think that some of the biggest advances that we are going to see in the field of neuroscience in the coming years will come from interdisciplinary collaborations of this kind.”

The Medical Scholars Program also has opened up unique opportunities for Mustroph to collaborate with her scientific peers at national and international conferences—including the Global Young Scientists Summit in Singapore in January. Mustroph was awarded funding to join 300 other young scientists and researchers from all over the world at the five-day, multidisciplinary summit, which covered topics related to chemistry, physics, medicine, mathematics, computer science and engineering.

The PhD students and postdocs who participated in the summit met with globally recognized science and technology leaders to discuss key areas of science and research, technology innovation and solutions to global challenges related to the summit’s 2015 theme, “Advancing Science, Creating Technologies for a Better World.” The summit is held annually to enable participants to learn, grow and contribute to the next wave of scientific breakthroughs.

The Medical Scientist Training Program at the College of Medicine's Chicago campus appealed to Ryan Lahey because it provided top-notch mentorship and research training.In Chicago, Lahey has been working with a network of scientists in various specialties “who are moving cardiovascular research forward to solve the many pressing problems that remain in the field of heart disease.”

“The spirit in Doug’s lab is very collaborative and cooperative,” says Lahey, who points out that these collaborations extend far beyond the College of Medicine. “We’ve collaborated with labs in Washington, Florida and Canada, and this collaborative approach has been very useful in terms of advancing our research.”

Although many people would regard eight years of intensive study and research as an interminable slog, Mustroph and Lahey are passionate about the paths they’ve taken, invigorated by their research and inspired by their mentors and peers.

“When I started the Medical Scientist Training Program, my biggest priority was to find a good mentor and get good research training,” says Lahey. “So I feel very fortunate that I ended up in Doug Lewandowski’s cardiac lab, which employs a number of very sophisticated research techniques. What inspired me most about Doug’s research was his multifaceted approach to studying the disease of heart failure. In terms of the big picture, heart failure is a huge problem in this country, with significant morbidity and mortality—so it is immensely rewarding to work on a disease that affects so many people.”

“I feel very fortunate to be in a program as dynamic as the Medical Scholars Program,” adds Mustroph, who will complete her MD/PhD studies in 2017. “I have a large group of more than 120 peers who are completing their PhDs in disciplines as diverse as bioengineering and sociology, and I am continually inspired by the incredible research that they are undertaking. The MSP has offered a rich environment for my intellectual growth—and prepared me well to bridge the gap between the clinical practice of medicine and the basic research that still needs to be done.”