Student researchers (from left) David Tran, Steve Blum, Elisha Garg, Daniel Croymans and Marko Spasic are counting on what they learn in the lab to make them better clinicians at the bedside.
By Dan Gordon
Photography by Patricia Williams
Elisha Garg has yet to begin her first clinical rotation, but the UCLA medical student's full-time participation as an investigator in a pair of closely watched clinical trials has her thinking ahead.
After completing her first two years, Garg is on leave from the David Geffen School of Medicine at UCLA to participate in a prestigious fellowship from the Howard Hughes Medical Institute. She is among 70 students from across the country in the HHMI Medical Research Fellows Program, a $2.5-million annual initiative to increase the training of future physician-scientists by sustaining medical students through an intensive year-long laboratory experience. The fellowship supports Garg's work in the lab of Roger Lo, MD, PhD, assistant professor of medicine/dermatology and molecular and medical pharmacology.
Garg is a key contributor to the effort by Dr. Lo's group to find ways to overcome resistance among patients with advanced melanoma to new drugs that target a mutation in the BRAF gene, V600, which is associated with about half of the cases of metastatic melanoma. BRAF inhibitors have been successful in treating patients with late-stage metastatic melanoma with this mutation, but inevitably these patients develop resistance and other unwanted side effects to the drugs. Garg is part of a team seeking to determine how the melanoma cells are eventually able to escape the effects of the drugs that target mutations in both BRAF and another implicated gene, MEK - work that could lead to improved targeted therapy.
After completing her research fellowship, Garg looks forward to returning to medical school for her third year, during which she will begin seeing patients and making connections between her laboratory experience and clinical practice. But she's also taking the longer view. "There are so many diseases that we don't understand or have cures for, and it's exciting to be contributing to finding answers that are going to affect patients in a very real way," Garg says. "In a couple of years, I'll be a physician seeing these patients, and I might have to tell them we have no good therapy for them. But because of all the research going into understanding the disease, by the time I'm 40 or 50 and seeing similar patients, I may be able to tell them that we do have a new drug that can help. That's very rewarding."
|Elisha Garg is investigating ways to overcome resistance among patients with advanced melanoma to new drugs|
In her pursuit of research experience, Garg is far from alone among her peers in medical school. Ninety percent of UCLA medical students participated in meaningful research in 2012, says Sarika Thakur, EdD, research director for the David Geffen School of Medicine at UCLA. That's a much higher percentage than at most other medical schools, says Dr. Thakur, who advises and assists students in identifying research opportunities and applying for programs and fellowships, many of which are funded by the dean's office of the medical school. Many of the students get their feet wet under the tutelage of postdoctoral fellows and faculty principal investigators, while some go on to independent studies. Many students end up as authors on peer-reviewed journal publications.
And some take it a step further. After spearheading a study in the Lincoln Heights community of East Los Angeles in which he found that exposure to online social networking sites had a negative impact on adolescents undergoing substance-abuse treatment, fourth-year student David Tran was selected as the only student among 300 MDs and PhDs to orally present his research at the American Psychiatric Association's 2012 meeting in Philadelphia. Tran, who conducted the study under the mentorship of Keith Heinzerling, MD, a UCLA internist and addiction-medicine specialist, was also chosen to participate in a media briefing on the findings. "David was able to combine a pursuit of scholarly research activities with providing community service and representing the university in an underserved neighborhood," says Dr. Heinzerling. "One of UCLA's purposes is to improve the quality of life for people living in Los Angeles, and students working in the community represent a very effective means for UCLA to make that vision real."
Third-year student Marko Spasic joined the laboratory of neurosurgeon Isaac Yang, MD, shortly after Dr. Yang established his research program to better understand and develop new therapies for glioblastoma, a deadly form of brain cancer. Spasic became the first UCLA medical student in years to receive two prestigious awards - the American Association of Neurological Surgeons Summer Research Fellowship and the Alpha Omega Alpha Carolyn L. Kuckein Student Research Fellowship - and he has played an active role in Dr. Yang's lab, working on a variety of projects that have led to nine published papers, with several more that have been accepted and numerous others in progress.
Daniel Croymans looks at how healthy lifestyle choices affect metabolic and cardiovascular disease.
"Given the amount of information that needs to be covered during medical school, there is minimal time in class dedicated to questioning things," says third-year student Daniel Croymans. "Research is a great way to dive into topics that you might get to touch only on the surface during your medical education, a way to develop analytic and critical thinking skills with the hope that you will enhance our current knowledge base. That's why I was attracted to it."
As part of the medical school's Pathways in Clinical and Translational Research certificate program, which connects students with mentors and offers educational opportunities as a way of building skills and promoting clinical and translational research, Croymans studies the efficacy and mechanisms by which healthy lifestyle choices prevent metabolic and cardiovascular diseases. For the last five years - beginning as a UCLA undergraduate and continuing through his master's program - Croymans has worked in the lab of Christian Roberts, PhD, a physiologist in the UCLA School of Nursing. As the first member of Dr. Roberts' lab, "Daniel has helped in all phases as a jack of all trades, most importantly leading the coordination of our first exercise trial."
Dr. Roberts is a strong proponent of medical students participating in the research process. "It's one thing to attend a class and read a study on a given topic," he says. "However, with a clear understanding of the basis for the ultimate conclusion of the research, one's frame of reference completely shifts. In addition, those who have significant research experience can gain a much deeper appreciation for everything that is involved in the research process, from the germination of an idea until the completed study is published."
Marko Spasic has been working with a neurosurgeon to better understand and develop new therapies for glioblastoma,a deadly form of brain cancer
Like many UCLA medical students who become intimately involved in research, Croymans is eyeing a career in academic medicine, and he says the Pathways in Clinical and Translational Research program has provided invaluable exposure to mentors whose footsteps he hopes to follow. But even for students who don't plan to make research part of their career, the experience provides a foundation for becoming an outstanding clinician, notes Owen Witte, MD, President's Chair in Developmental Immunology, Microbiology, Immunology & Molecular Genetics and director of UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
"The best clinicians I know are the ones who are both scientifically literate and scientifically practiced," Dr. Witte says. "The genetics, physiology and biochemistry involved in decisions about prescribing a drug or ordering a diagnostic test are much better understood when the physician's training includes the conduct of science rather than just reading about the results of science. That's why we're seeing more and more students becoming involved in research. It helps them later, as the complexity of medicine changes due to the influx of more scientific principles."
It should come as no surprise that students interested in obtaining significant research experiences would be drawn to UCLA by its standing among the world's elite academic medical centers. But more than merely being located in a research-centered environment, UCLA offers students myriad opportunities and support designed to encourage them to take part.
For the summer after their first year, students can apply for any of approximately 20 UCLA-funded fellowship programs that support research, as well as one of the national summer fellowships. "Students receive a stipend that enables them to gain exposure to a variety of research experiences early on," Dr. Thakur explains. At that time, many find their niche and decide to prolong their association with a lab in some form.
Second-year students are eligible for funding to attend the annual Western Student Medical Research Forum in January, where they can present their work to faculty and other medical students from as many as two-dozen universities throughout the United States. Students who enroll in the MD/PhD program take time after their second year to complete their PhD before returning to the medical-school curriculum. The Student Affairs Office assists all students in the process of applying for the research fellowships, whether they're funded by UCLA or an outside source.
Because many students' stints in the lab are short and it takes time to train them, Dr. Witte tends to view bringing students in as more of an investment in the future of science and medicine than as a benefit to his lab. "But there are exceptions," he says. "When it does help, it's not in the provision of labor, but in the provision of a different point of view. People who are trained in the medical arena bring a certain type of questioning and interest to basic-research problems and a perspective on how to take the basic research back to the clinic."
Steve Blum’s research has focused on studying the DNA of tissues from cancer patients to determine if prostate and ovarian tumors contain a genetic mutation associated with the development and proliferation of certain tumors.
One such exception is Steve Blum, a second-year medical student who began attending meetings and learning procedures and protocols for Dr. Witte's lab in January of his first year, then hit the ground running in May, working full-time in the lab as one of 33 recipients of the Howard Hughes Medical Institute Summer Scholars program award. Blum knew Dr. Witte prior to medical school, having met him when Blum worked for a firm that evaluated and developed early-stage biotechnology companies. After seeing research at all phases from his perch in the biotech field, Blum decided he wanted to go to a medical school where he would be prepared to address clinical questions through research. "Dr. Witte was a great mentor for me when I was applying, and when I began searching for research opportunities, he helped me to explore a number of prospects before I determined that his lab was an ideal choice for me," Blum says.
Blum's summer project focused on studying the DNA of tissues removed from cancer patients to determine if prostate and ovarian tumors contained a mutation in the gene encoding Trop2 - a protein shown by Dr. Witte's lab to be involved in the development and proliferation of certain tumors. He has continued to work part-time in Dr. Witte's lab during the school year. "Steve is exceptional at many levels," Dr. Witte says. "He is doing all that I would hope a medical student working part-time could do - interacting well with others, picking up new technologies, and finding a niche for himself where he can be a valuable component of the team."
The time spent in Dr. Witte's lab has confirmed Blum's desire to pursue a career in academic medicine, balancing research and patient care. "In the past, I had done more theoretical types of projects," Blum says. "One of the things I've gained from this experience is the opportunity to work with clinical material and questions that are closer to human biology. It's been rewarding to learn the basic-science approach to clinical issues - how you talk through the problems, formulate questions and take on the challenges. The great thing about this type of research is that when you solve a problem you can translate it into something that can help patients. That's very motivating."
Marko Spasic finds himself drawn to research for similar reasons. "I love the camaraderie and the challenge of problem-solving and answering questions," he says. "But what really pushes me is the knowledge that we're answering questions that can have an impact on patient care."
He joined Dr. Yang's lab in the fall of his first year and, with his two fellowship awards, has helped to move the lab closer to its goal of developing an effective therapy for glioblastoma, the most common primary malignant brain tumor, which is associated with a life expectancy of a little more than a year and has few treatment options. One of the focuses of the lab is to assess the potential of new immunotherapy strategies for treating glioblastoma, including the use of vault nanoparticles - naturally occurring structures in the body that appear to be effective in helping to direct immune cells to tumors. Spasic's projects have ranged from laboratory studies assessing the impact of targeting glioblastoma stem cells that include CD133, a marker for more aggressive malignant cells, to clinical research evaluating the efficacy and side effects of new therapies for brain tumors.
David Tran is examining the impact of social networking on adolescents undergoing treatment for substance abuse
Beyond the research experience per se, Spasic and other students interested in blending research and clinical practice in their careers benefit from mentors who are doing just that. "I love dissecting the problems, but I also love interacting with patients, and it will be challenging to find the right balance between the two," Spasic says. "Dr. Yang is a great example of that. He leads a productive lab and is incredibly dedicated to mentoring students, and at the same time he is constantly making himself available to patients. He serves as an inspiring example for what I want to become."
The inspiration goes both ways. "Medical students bring so much energy, enthusiasm and fresh ideas to research," says Dr. Heinzerling. Tran is one such student. He has kept himself busy on a number of research projects in addition to the study on the effects of social media on adolescents in substance-abuse treatment. Tran is one of the lead researchers in designing and running a longitudinal study measuring the knowledge and attitudes of UCLA medical students regarding gay, lesbian, bisexual and transgender persons; co-principal investigator of a qualitative study exploring the experiences and perspectives of black males pursuing a career in medicine; and was one of the lead researchers on the Diversity Initiative Executive Research Team, which developed a statement reflecting the values and goals for UCLA Health on diversity and inclusion issues.
Tran, who received the Albert Schweitzer Fellowship and Jeanne Spurlock Research Fellowship in Substance Abuse and Addiction from the American Academy of Child and Adolescent Psychiatry Association to support the social-media study, worked with Dr. Heinzerling to identify potential triggers that could cause recovering addicts to experience a relapse, and decided to investigate the impact of social-networking sites. As a follow-up, the research team is studying the feasibility of harnessing the power of social media into something positive by creating online support groups through Facebook.
As an undergraduate, Tran engaged in basic research; while he enjoyed it, he found his calling at UCLA when he was introduced to community-based health-services research. He is concurrently pursuing a master's degree in public policy and is part of the UCLA-PRIME program, which trains future physi-cians who will address the needs of medically under-served communities, with plans to complete a residency in psychiatry and pursue a career in which he can influence mental health policy. "To be able to think about a problem and try to identify outside-the-box solutions is exciting," he says. "Studying ways to improve health at the community level provides a great complement to learning things like basic pathophysiology."
Under the guidance of Dr. Roberts in the UCLA Exercise and Metabolic Disease Research lab, Croymans has parlayed work he began as a master's student - including leading a small clinical trial examining the effects of resistance training on arterial function, glucose tolerance and overall metabolic health; and a cross-sectional study assessing the relationship between training status, body composition and metabolic-disease risk - into independent studies that are being submitted to and published in peer-reviewed journals. He is interested in ultimately taking his findings into the community in an effort to explore how interventions to increase exercise can best lead to meaningful change.
"It used to be that to be a good physician, you just needed to know everything," Croymans says. "But the knowledge base has grown so dramatically that that's no longer the case, and now the real power is in being able to critically appraise and evaluate the knowledge that's put before us toward an evidence-based practice that improves patient outcomes and quality of life. Research sets a strong foundation to do that, and more than other programs I looked at, UCLA provides the freedom and support to become involved in research in meaningful ways."
Dan Gordon is a regular contributor to U Magazine.