This month, we are featuring Chris Lee, PhD, who was awarded a $375,000 Rosenau Family Research Foundation grant in 2025 for his project titled “Molecular characterization and pathogenicity assessment of common variants of uncertain significance in Krabbe Disease”, which is studying whether measuring GALC enzyme activity and levels of the toxic substance called psychosine in cells can help determine whether certain genetic changes cause the disease.
Chris Lee, is a neuroscientist and molecular biologist whose research focuses on the molecular mechanisms and experimental therapeutics of neurodegenerative diseases. While on faculty as an Assistant Professor at the Mayo Clinic, Dr. Lee initiated his research program on Krabbe Disease (KD). He led studies uncovering how specific genetic mutations in the GALC gene lead to dysfunction of the galactosylceramidase (GALC) enzyme. His pioneering work has shown that GALC deficiency is mutation-dependent and can result from mechanisms such as nonsense-mediated mRNA decay, protein misfolding, or impaired trafficking.
Since joining the Biomedical Research Institute of New Jersey (BRInj) and Atlantic Health System, as a faculty scientist and a lead researcher, respectively, in 2017, Dr. Lee has expanded his research program with critical support from the Rosenau Family Research Foundation. This funding enabled his team to develop a novel GALC immunoassay, which can detect endogenous GALC protein in human samples. Using this tool, Dr. Lee has demonstrated that GALC protein levels may differentiate infantile- from later-onset KD – a finding published in Neurobiology of Disease.
Dr. Lee’s lab also generated a GALC knockout cell model to functionally evaluate disease- associated GALC mutations. In a recent study, his team characterized 36 missense mutation variants and found a strong correlation between residual GALC activity and clinical disease severity, providing a promising prognostic indicator for KD. This work was recently published in the Journal of Biological Chemistry.
Dr. Lee is now leading a new initiative to assess the pathogenicity of GALC variants of uncertain significance (VUS) – a growing challenge as Krabbe disease has been added to the Recommended Uniform Screening Panel (RUSP) for newborn screening in the U.S. Leveraging his lab’s tools and expertise, this project aims to provide much-needed functional insight to improve prognostication for at-risk infants.