Since 2003, Mei Wang Baker, MD, has been a scientist with the Newborn Screening (NBS) Program at the Wisconsin State Laboratory of Hygiene (WSLH) and served as its co-director from 2013 to 2021. She became the director of the Newborn Screening Program in 2022. Baker also joined the Department of Pediatrics in 2007, where she is now a professor in the Division of Genetics and Metabolism. “I knew I wanted to work with human genetics early on,” Baker explained. “Genetics breakthroughs can be rapidly translated to clinical diagnoses and treatments. Research results can quickly become practical and beneficial for affected patients.”
Every year, from the approximately 60,000 babies born in Wisconsin, a health care practitioner from the birth hospital (or the midwife or birthing attendant) takes five drops of blood from the infant’s heel on special filter paper 24 to 48 hours after the birth. The bloodspot card is submitted to the WSLH via courier, where it is screened for serious congenital conditions, as mandated by Wisconsin statute.
The WSLH only screens for conditions for which treatments exist. It tested only for phenylketonuria (PKU) in 1965 and added tests for more conditions throughout the decades —and has also participated in research studies. Today, WSLH tests for 48 congenital disorders.
Baker brings considerable expertise to her role in NBS; she also leads genetic research projects that have resulted in significant outcomes, including notable new screening methods for congenital diseases. Her 2005–2007 fellowship in clinical biochemical genetics at UW–Madison greatly enhanced her skills and knowledge with its focus on applications of molecular and biochemical technology in NBS, and on public health genetics and genomics. It further advanced Baker on her desired path toward conducting significant genetic research that could be quickly translated to public health practice. Three examples of Baker’s significant contributions to the field include innovative and translational research in cystic fibrosis (CF), Severe Combined Immunodeficiency (SCID), and Spinal Muscular Atrophy (SMA).
When Baker arrived at WSLH, bloodspot screening for CF had already been established in Wisconsin in 1995 and was conducted nationwide in all states by 2010. The pathbreaking randomized clinical trial, begun in 1984, of CF newborn screening conducted by Philip Farrell, MD, PhD, emeritus dean and professor in the Division of Pulmonology and Sleep Medicine, and his research team had shown that newborn screening combined with the trial’s nutritional treatment was beneficial for affected patients. However, CF research has continued beyond 1995, revealing more disease-causing variants of the CFTR (cystic fibrosis transmembrane conductance regulator protein) gene.
“We are using next-generation sequencing technology (NGS) in our current CF screening, which allows us to screen simultaneously for more disease-causing variants,” Baker explained. “We can now detect 689 disease-causing variants of the CFTR gene. And it is relatively easy now to update our software and screen for more variants without re-doing the assay. The detailed variant information helps clinicians develop more precision treatment plans.”
In January 2008, Baker initiated the first newborn screening in the world at WSLH for Severe SCID, a primary immunodeficiency disorder that is invariably fatal without timely stem cell treatment. She had recognized the need for a robust test for SCID that could be used in the high-volume and quick turnaround public health newborn screening laboratories. Her new method could accommodate the large numbers of screens processed by these labs; it also produced a 10-fold fewer number of false positive results.
“My work paved the way for Wisconsin to provide the first statewide SCID screening in the world,” Baker said. “The Wisconsin experience on newborn screening for SCID was fundamental to SCID’s addition to the Recommended Uniform Screening Panel.”
The implementation of newborn screening for spinal muscular atrophy (SMA) is another example of Baker’s successful efforts to translate research for the benefit of public health. SMA results from a lack of survival motor neuron (SMN) proteins, which are essential for muscle movement. People with SMA do not make enough SMN protein because the gene is either absent or distorted. People with SMA lose muscle function at varying rates.
Baker and her research team developed a newborn screening test for SMA at the WSLH. Baker’s unique comprehensive approach provided both timely SMA detection and confirmation as parts of the algorithm for SMA newborn screening. This allowed for timely clinical follow-up, family counseling, and treatment planning. WSLH NBS implemented SMA screening in October 2019.
Baker continues her research developing blood tests for congenital disorders that may become treatable. She is currently developing an NBS assay for Angelman syndrome (AS), a rare disorder (1 in 15,000 births) caused by the UBE3A gene’s loss of function. Symptoms resemble those of autism and cerebral palsy. Effective gene therapy treatments for this disease are expected in the near future.
As technology becomes more advanced, gene therapies for genetic disorders may be developed more quickly than in the past. Baker is determined to be ready with effective screening protocols, and she is proud that WSLH’s newborn screening program is a pioneer.
“Wisconsin’s newborn screening program is viewed as being at the forefront in the field,” Baker explained. “Our association with the university gives us a huge advantage, and I get a lot of support from the department. We are in a position to continue our work and to set an example. Our forward thinking allows us to obtain funding to do testing development.”
Baker plans to have potential screens ready when transformative treatment becomes available — to be proactive rather than reactive. “I am an optimist,” she stated.
In 2022, The Association of Public Health Laboratories (AHPL), at its Newborn Screening Symposium, awarded Baker the Everyday Life Saver Award in Newborn Screening. The nomination letter stated, “Dr. Baker has made great contributions to expanding and improving the screening of newborns by public health agencies in Wisconsin and nationally through her research in public health genetics and genomics, which focuses on applying and translating advanced biochemical and molecular technologies into routine newborn screening practice.”
Photo by Bob Gordon/Department of Pediatrics