UM School of Medicine Scientist Receives NIH Award to Study Heart Disease Related to Down Syndrome

Researchers receive new federal funding to identify genes associated with congenital heart defects that occur in half of patients with Down syndrome.

The National Institutes of Health announced today that Zhe Han, PhD, Associate Professor in the Department of Medicine at the University of Maryland School of Medicine (UMSOM), will be awarded a supplemental funding of $772,500 to the ongoing $1.75 million NIH-funded project in Dr. Han’s lab for studying genes involved in Congenital Heart Disease. This supplemental funding will support the research to identify the genetic causes of Congenital Heart Disease that occur in half of all patients with Down syndrome. The goal is to identify genes associated with Down syndrome congenital heart disease and to study the molecular mechanism underlying the cardiac defects. This can potentially lead to better treatments for these heart abnormalities which are a major cause of mortality in those with Down syndrome.

The funding is part of an NIH initiative called Investigation of Co-occurring Conditions Across the Lifespan to Understand Down Syndrome (INCLUDE) that was launched last year in response to a Congressional directive calling for a new NIH initiative to address critical health and quality of life needs for individuals with Down syndrome. It is also intended to investigate the risk and resilience factors for conditions, like congenital heart disease, that occur in those with and without Down syndrome.

“Individuals with Down syndrome are both affected by and protected against many of the conditions that afflict the general population,” said NIH Director Francis S. Collins, M.D., Ph.D. “By improving our understanding of the basic biological mechanisms of Down syndrome, and making clinical trials more accessible and specifically tailored to individuals with Down syndrome, we expect that research from the INCLUDE project will benefit everyone."

Dr. Han and his team will use the award money to generate and characterize Drosophila “fruit fly” models of congenital heart disease in patients with Down syndrome based on previously identified areas on human chromosome 21, and identify the specific genes responsible for causing congenital heart disease in Down syndrome patients.

“Since early heart development is controlled by an evolutionarily conserved genetic network, preserved from flies to humans, we can use Drosophila to identify the genes that cause congenital heart disease in Down syndrome patients.” Dr. Han said. “Identifying these genes is the key to understanding the disease mechanism and to develop targeted treatments in the future.”

Recently arriving at UMSOM this summer as a STRAP (Special Trans-Disciplinary Recruitment Award Program) recruit from Children’s National Health System in Washington DC, Dr. Han is a leader in the field of using Drosophila to model human diseases. His lab generated tools and methods in Drosophila to efficiently study genes involved in heart development and congenital heart disease --the most common birth defect -- based on genetic sequencing data from children born with heart defects. Using this high-throughput approach, Dr. Han’s lab studied the function of about 200 genes of interest identified from congenital heart disease patients, and provided the functional data relevant for heart development for these genes.

NIH has set aside $22.2 million in funding for the INCLUDE project, for conducting targeted high-risk, high-reward basic science studies on chromosome 21. (Three copies of chromosome 21 are present in those with Down syndrome.)  The University of Maryland School of Medicine is one of 25 institutions that received an NIH award from the INCLUDE project in fiscal year 2019.

"I am so pleased that the NIH continues to recognize the abilities of our School of Medicine scientists as leaders in their field of basic research, in this case to further the understanding of congenital diseases,” said Dean E. Albert Reece, MD, PhD, MBA, Vice President for Medical Affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor at UMSOM. “Once we are able to identify which genes are important for heart development and how they work, there is the potential to prevent these conditions from being passed on to the next generation through gene-editing techniques.”

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research.  With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and more than $540 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu