Thursday, June 14, 2018

By Roxanna Van Norman 

Manpreet Singh, MD, MS likes to think of a child as a whole person, not just examining one organ system, like the brain or another, when she’s in the clinic or the lab. As an assistant professor of psychiatry and behavioral sciences in the Division of Child and Adolescent Psychiatry and Child Development at the Stanford School of Medicine, Dr. Singh has long been fueled by her passion of treating the biological, psychological, and social contributors to a child’s health. She has a specialized interest in understanding children who are at risk for serious mood disorders that can last a lifetime.

Dr. Singh and her academic team in the division's Pediatric Mood Disorders Program recently demonstrated a possible link between pediatric obesity and depression in the brain. “The study is a very good example of the interface between the mind and body, and how maladapted eating behavior, sedentary lifestyle, and challenges with regulating emotion are all governed by the brain,” Dr. Singh explains, who serves as the director of the program.

With the growing public concern over the childhood obesity epidemic and mental health, Dr. Singh says she and her team are looking at ways to better characterize children by using multi-modal assessments, and analyzing their brains, behaviors, and family structures. That’s why supportive academic environments are essential for clinician scientists like herself, she explains; having access to patients and an established research infrastructure can directly inform the work and accelerate discovery.

Dr. Singh points out, “In general, we have very few studies that inform evidence-based treatments for children. [Yet], we are at an institution that attracts interest regionally and globally, to provide specialized care to patients and families who are struggling to find answers to complex and chronic symptoms that tend to be difficult to treat.” She is also a child and adolescent psychiatrist at the Lucile Packard Children’s Hospital Stanford.

Inspired to address the significant unmet needs of youth today, in the context of serious health problems that are stigmatized and underserved, Dr. Singh’s dream is to prevent major health problems from progressing into adulthood. “My pie in the sky goal is to prevent diabetes and cardiovascular disease by treating depression early,” Dr. Singh says. “If we can achieve that goal, then we can make a significant impact on not just a child's mental health, but a child's overall health and well-being.

The first grant for studying children at risk for mood disorders

Dr. Singh completed her residency training in Pediatrics, Psychiatry, and Child and Adolescent Psychiatry at Cincinnati Children’s Hospital Medical Center and was recruited to Stanford in 2007 as a postdoctoral fellow. Early into the second year of her postdoctoral study, she applied for and received her first pilot award of $35,000 in 2008 from Stanford Child Health Research Institute (CHRI) to support her project looking at the neurochemical characteristics of youth at risk for major mood disorders using magnetic resonance spectroscopic (MRI) imaging. That small seed grant would lead to ten years of research supported by CHRI and incredible opportunities.

“The pilot award mechanism through CHRI taught me important lessons in grant writing, and how to effectively land my ideas, and make sure that they had an impact,” Dr. Singh expresses. And as with anything, she adds, grant writing takes iteration and time to develop those skills. These lessons helped prepare her to develop and to prepare to write for larger, in-depth research proposals to external funding agencies, like the National Institute of Mental Health (NIMH).

Her early research evaluated the neural and genetic profiles for mood disorders and emotion dysregulation in kids who had a family history of bipolar disorders. Based on the pilot work, she received the Career Development (K23) Award through NIMH. To date, she has received a total of $570,000 from CHRI to support her work in childhood mood disorders. This has enabled nearly $6 million of direct external funding from the NIMH and other agencies. “Thanks to the early support that I received from the CHRI, I have been able to build a portfolio of research with increasing impact,” she explains.

With the help of funding that I've received leading up to this work, I've now been able to ask that question and have support from the National Institute of Health to evaluate children who struggle with maintaining a healthy weight and depressive symptoms

One success after another

With the NIH K23 Award, Dr. Singh continued her research by tracking 50 children and their state of health from the perspective of their brain development, genetic profiles, and the way they regulated stress.

In 2013, the CHRI named Dr. Singh the Akiko Yamazaki and Jerry Yang Faculty Scholar in pediatric translational medicine; the award comes with $500,000 of funding support over five years. With this funding, she was able to add a longitudinal component to the work she had been doing and expand her sample size. In addition to the 50 kids she evaluated during her K23, she enrolled another 100 kids and followed all of them over several years to understand their developmental trajectories.

Subsequent to her Faculty Scholar Award, Dr. Singh was awarded 3 NIH R01s.  “These next studies are going to lead to a deeper understanding of how youth move from a state of health to a state of vulnerability or resilience, and this information can help us make the right decisions for patients and families, and lead to more precision health outcomes,” she says. 

According to Dr. Singh, exposures to adverse life experiences, challenges with emotional regulation, or struggles to maintain a healthy weight may all have an impact on brain development. One of her simple questions is, can identifying common brain pathways for these frequently co-occurring problems lead to the discovery of novel treatments? Possibly, according to her recent publication.

“With the help of funding that I've received leading up to this work, I've now been able to ask that question and have support from the National Institute of Health to evaluate children who struggle with maintaining a healthy weight and depressive symptoms,” says Dr. Singh.

What it means to be a translational scientist

Earlier this year, the CHRI sponsored Dr. Singh to participate in the 10th annual Eureka Institute for Translational Medicine International Certificate Program in Sircusa, Italy, which turned out to be career game changer for her.

She spent a week in April at the Eureka Institute for Translational Medicine that provides professional and training opportunities for mid-level career scientists in translational medicine. As one of the educational offerings provided by the CHRI to its members, the CHRI sponsored five Stanford participants, including Dr. Singh, to participate in the annual certificate course program. Eureka participants receive a deep and broad overview of the latest developments in translational medicine and other related topics, including marketing to drug companies, drafting a patent, and developing skills that are essential to becoming a translational researcher.

“I am amazed by the culminating journey that led to the Eureka course, a CHRI opportunity that was the icing on the cake,” she says. “I started off with a pilot idea and now have come ten years later toward an independent, translational, and multidisciplinary research program that is dedicated to improving the lives and well-being of children, adolescents, and families with or at risk for developing major mood disorders.”

As the recipient of multiple grants, she already had an idea of what it meant to be a translational scientist. But after the program, she now has a better understanding of what it means to be a faculty scholar in pediatric translational medicine. “The translational science course came at a critical time in my career,” she says. Dr. Singh was at the halfway mark of her three NIH Research Project Grants (R01-level) around the same time and was keenly seeking ideas for how to push her science to the next level toward the discovery of novel treatments.

And going back to treating the child as a whole, she believes the Eureka program helped defined for her what it meant to be a translational scientist. “Translational medicine isn't just moving from bench to bedside; it's not just the fact that I use neuroimaging to better understand, and probe questions about childhood and brain development,” she reflects. The program helped to solidify her approach, namely, that she is interested in advancing the understanding of why kids get sad, from a molecular perspective to macro behavioral view. 

The Eureka course taught me to engage with the end game in science, which is a long-term vision rather than a vision for a specific research study or project. Engaging with this end-game has helped me realize the true potential and impact of the work we must do to meet the unmet needs of our patients.

Bringing it back home

Her trip to the beautiful city of Siracusa, Italy for the course reignited Dr. Singh’s appreciation for her work and the resources and opportunities that Stanford affords to its faculty and staff. “It enabled me to take some space away from my work environment to understand why Stanford is the best place to build my career,” she says. “I can now also leverage a global community of translational collaborators who can teach me what I don’t know and consider alternative approaches to solving the universal problems we face in science.

Energized by this experience, she’s also looking forward to continuing this momentum at Stanford. She intends to put her learning in translational medicine into practice, by continuing to build and support her team, and cultivating new collaborations with translational scientists in disciplines she hadn’t previously considered.

“I came home with a vision to accelerate the discovery for a novel treatment for depression in kids,” Dr. Singh expresses. “And now I am assembling a team to start the process of potentially patenting our idea.” She also hopes to bring the course back home and to provide translational science teaching on campus.

"The Eureka course taught me to engage with the end game in science, which is a long-term vision rather than a vision for a specific research study or project,” Dr. Singh concludes. “Engaging with this end-game has helped me realize the true potential and impact of the work we must do to meet the unmet needs of our patients.”

Roxanna Van Norman is the marketing manager for the Child Health Research Institute.