When the National Institutes of Health (NIH) established the nationwide KL2 educational programs, one of the overriding goals was to help new clinical and translational investigators sharpen their abilities in teamwork.

But it was precisely such a cross-disciplinary mix of expertise that led Mimi Kim, MD, a pediatric endocrinologist and alumna of the SC CTSI KL2 Scholar program, to wonder if a novel application of magnetic resonance imaging (MRI) could also be used to understand thyroid dysfunction in children, one of her areas of clinical and research focus. 

Mimi Kim, MD

While she was a KL2 scholar, Kim, assistant professor in the division of Pediatric Endocrinology and Metabolism at the Children’s Hospital of Los Angeles (CHLA) and Keck School of Medicine of USC, worked with a team of researchers to study a type of fat called brown adipose tissue – also known as brown fat, due to its color.

It really takes a village to make a researcher. By protecting time in busy professional schedules for researchers to find mentorship and collaboration, as well as the coursework and seminars, the KL2 program has become a self-sustaining community that provides unique support to rising clinical researchers, said Kim. 

Unlocking the secrets of the good fat

Brown fat is increasingly drawing the interest of medical researchers who study metabolic and endocrine issues, such as obesity and diabetes. But it has only been in the past couple of years that MRI physicists and engineers developed methods to visualize brown fat.

Until recently, it was believed that in humans, only babies had brown fat (hibernating mammals also possess the tissue) and that its main purpose is to generate body heat. But researchers have since found that brown fat remains in the body through childhood and adulthood – and that it appears to play important roles in various metabolic functions.

"It's a very interesting tissue, but until we had these MRI applications, we had no way to safely and non-invasively study it in pediatric patients and healthy people," said Kim. "The MRI technology opens up a whole new avenue to study the function of brown fat function in metabolic disorders and hopefully develop therapies."

The fat we grumble about when our clothing starts to feel too tight after a season of too much eating and not enough exercise is white fat.  White fat evolved to store excess calories for the long term. But brown fat is richly supplied with blood vessels and mitochondria – tiny chemical power plants within the body's cells – making it a ready source of energy. In fact, thinner people actually have more brown fat, and obese people less.

"These kinds of associations are leading a lot of researchers to look for therapies for obesity and other problems based on brown fat," said Kim. "So we have to understand the mechanisms and triggers that activate it and how it works in the body."

The importance of teamwork

While in the KL2 program, Kim was part of a group of investigators studying cardiovascular disease risk in children with congenital adrenal hyperplasia (CAH), a genetic glandular disorder. The group she worked with included a mix of clinicians and radiologists – similar to the team studying brown fat – and reflected the KL2 program's recognition of the interdisciplinary teamwork that is so critical in clinical and translational research.

"I'm an endocrinologist, so my strength is in looking at things from a metabolic perspective," said Kim. "Meanwhile, the MRI engineers and radiologists know more than I ever will about imaging. But having people come together from different backgrounds enables us to find that innovative sweet spot and look at research questions from new directions." 

Intrigued by her experience in the CAH study, Kim wanted to continue to apply innovative imaging approaches to investigate the link between brown adipose tissue and thyroid disorders in children. But Kim needed the expertise of radiologists and MRI engineers who were already experienced with brown fat research to help her conduct her thyroid investigation.

The thyroid, a gland located in the neck, controls how the body uses energy, forms proteins, and regulates other hormones, and is a critical part of the body's metabolism.

Kim's thyroid research project has involved 25 children from CHLA with thyroid disorders. Kim and her co-investigators have found a number of associations between thyroid hormones and brown fat.

The brown fat association may be directly linked to the body temperature regulation difficulties that children with thyroid disorders often experience, said Kim. People with hypothyroid issues, or low thyroid hormone function, tend to feel physically cold in temperatures most people find comfortable. And people with hyperthyroidism, or high thyroid function, often feel overly warm.

As the research team prepare to publish the findings, Kim said her research could not have proceeded as efficiently – if at all – without the teamwork and mentorship that the KL2 program is structured to enable. "The group was more powerful than the sum of its parts," she said. 

By protecting time in busy professional schedules for researchers to find mentorship and collaboration, as well as the coursework and seminars, the KL2 program has become a self-sustaining community that provides unique support to rising clinical researchers, said Kim. "It really takes a village to make a researcher."

The study's principal researchers include:

• Mitchell Geffner, MD, a pediatric endocrinologist at CHLA and professor of pediatrics at Keck Medical School. He was also Kim's primary KL2 research mentor and still mentors her in her clinical research projects.
• H. Harry Hu, PhD, a physicist and MRI expert at the Saban Research Institute of CHLA and a pioneer in MRI visualization of brown fat.
• Vicente Gilsanz, MD, a pediatric radiologist at CHLA with extensive experience researching brown fat in children and adolescents, and a co-mentor to Kim on the CAH study.

SC CTSI is part of the 62-member Clinical and Translational Science Awards (CTSA) network funded through the National Center for Advancing Translational Sciences (NCATS) at the NIH (Grant Number UL1TR000130). Under the mandate of “Translating Science into Solutions for Better Health,” SC CTSI provides a wide range of resources, services, funding, and education for researchers and promotes online collaboration tools such as USC Profiles.