Four Clinical Scholars Win Research Grants

Four researchers have received grants, each worth up to $30,000, through the Clinical Scholars Program, which provides aspiring clinical scientists at Cedars-Sinai with mentors, training and funding to further their scientific endeavors.

While the 2014 winners of the annual, competitive awards are studying diverse disorders, they share a common goal: to alleviate human suffering. The grants — the Eigler-Whiting-Mann Award and the Cedars-Sinai CTSI Clinical Scholar Grant — will help these scientists generate pilot data to support applications for career development and mentored research awards from the National Institutes of Health and other funding agencies.

In the five years since Cedars-Sinai established the Clinical Scholars Program, "we have seen the number of extramural training grants go up substantially for our young investigators," said the program's director, C. Noel Bairey Merz, MD. "Within a very short period of time, the program has paid for itself." Bairey Merz also is professor of medicine, medical director of the Barbra Streisand Women’s Heart Center and director of the Preventive and Rehabilitative Cardiac Center at Cedars-Sinai's Heart Institute.

Below are profiles of this year's winners and their projects:

Irene Kim, MD

(Cedars-Sinai CTSI Clinical Scholar Grant)

Just knowing that a drug works rarely satisfies medical scientists. They want to know how it works. For Kim, this quest involves tocilizumab, an FDA-approved drug therapy for autoimmune disorders, such as rheumatoid arthritis.

Her preliminary data indicates that treating mice with tocilizumab reduces antibody development, Kim said. The drug appears to inhibit a receptor for IL-6, a protein that has been implicated in the development of antibodies. Her new research, also using mouse models, seeks to discover the mechanisms of action by which inhibiting the IL-6 receptor prevents the formation of alloantibodies.

Kim said she hopes her research eventually can be applied to organ transplants, especially to help a sub-group of patients whose highly sensitized immune systems reject transplants. If their immune systems can be fine-tuned to be less sensitive, such patients might become transplant candidates.

"This grant is extremely important to my work," said Kim. Her mentor is Stanley Jordan, MD, director of kidney transplantation and transplant immunology at the Kidney and Pancreas Transplant Center.

 

Stephen Shiao, MD, PhD

(Eigler-Whiting-Mann Award)

Can the presence of certain fungi and bacteria in the intestines influence the outcome of radiation therapy for breast cancer? Shiao is trying to find the answer.

He is intrigued by recent published studies suggesting that the so-called microbiome in the gut, by providing regulatory signals to immune cells, may affect how the immune system responds to disease at other body sites. That's important clinically, he explained, because "there is increasing evidence that radiation and chemotherapy don’t work just by directly killing tumor cells but by stimulating the immune system to recognize tumor cells and develop a response."

Working with his mentor, David Underhill, PhD, associate director of the Division of Immunology Research in the Department of Biomedical Sciences, Shiao plans to use a murine model of breast cancer to study the effects of radiation therapy combined with antibiotics or antifungals to deplete bacteria or fungi from the gut. His hypothesis is that depleted levels of these organisms will make the radiation treatment less effective.

Shiao said he hopes his research one day may lead to new immune-based therapies for breast cancer. His prior awards include a $10,000 CTSI core voucher earlier this year to perform gene sequencing of the gut microbiome and a $30,000 CTSI Scholar Seed Grant last year to study how radiation treatment to the abdomen and pelvis impact intestinal health.

 

Namita Singh, MD

(Cedars-Sinai CTSI Clinical Scholar Grant)

Clinicians face a frustrating obstacle in treating children for inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis: About half of their patients stop responding within a year to the most effective therapy, a monoclonal antibody known as infliximab. What if doctors could predict which patients are at risk? Singh is trying to find a way to do that.

Using data from Cedars-Sinai patients, Singh is building a model to identify factors that are most predictive of losing response to infliximab. "Utilization of such a model will impact the way we manage patients and result in optimized, individualized dosing of infliximab," she said.

Singh plans to validate her model with another patient group and then see if it can be enhanced by measuring the amount of calprotectin protein in stool samples — a method for monitoring IBD — and obtaining an ultrasound to assess the thickness of the bowel wall and other disease indicators. Singh's mentor is Marla Dubinsky, MD, director of the Pediatric Inflammatory Bowel Disease Program.

Earlier this year, Singh also won a $3,000 Clinical Fellows Award for Excellence in Research at Cedars-Sinai for her work on inflammatory bowel disease.

 

Janet Wei, MD

(Eigler-Whiting-Mann Award)

A new risk assessment calculator issued by the American Heart Association has put renewed focus on early intervention to prevent or delay heart attacks and strokes. But how can clinicians best determine who really needs treatment or who will benefit from treatment? Wei believes better tools are needed for risk stratification.

Her research focuses on one of these tools — magnetic resonance imaging (MRI). A new, speedier version of this established technology, developed in the laboratory of Debiao Li, PhD, director of the Biomedical Imaging Research Institute, provides better resolution and compensation for the heart's motion, she explained.

Wei plans to use this improved technology to measure the volume of plaque and identify high- risk plaque features in arteries — key predictors of atherosclerotic cardiovascular disease events. She is exploring ways to combine plaque measurements from three vascular beds — the coronary arteries, the carotid arteries and the femoral arteries — into a global assessment of cardiovascular risk. Such an assessment, she hypothesizes, would be more accurate than one based on a single vascular bed alone.

"It is very exciting to receive this award so that I can start my project," Wei said. She hopes that her research will lead to future improved cardiovascular risk assessment and monitoring of atherosclerosis treatment response for a personalized medicine approach. Her other honors include winning a Cedars-Sinai Sports Spectacular Endowed Fellowship Award last year and Clinical Fellows Award for Excellence in Research in 2012. Her co-mentors are Li and Bairey Merz.