University of Missouri

Biography

Monique Lorson’s research has focused towards understanding how mutations in IGHMBP2 result in two distinct diseases SMARD1 and CMT2S. In collaboration with the C. Lorson laboratory, they have worked on the development of a novel CMT2E mouse model and a vector-based approach to reduce NEFL-mediated disease severity (Perez Lopez et al., 2025; Perez Lopez et al., 2025). She also has active collaborations with Drs. Kamal Singh (IGHMBP2 biochemistry) and Nicole Nichols (respiration).

Towards understanding the role of IGHMBP2 mutations in generating disease, they generated six Ighmbp2 mouse models that are based on SMARD1 and CMT2S patient mutations. Importantly, the Ighmbp2D564N/D564N mouse was the first SMARD1 model published that exhibited the defining clinical symptom of SMARD1, respiratory distress as well as SMARD1 pathology (Smith et al., 2022). Their laboratory also identified the first modifier of SMARD1 disease pathology, ABT1 (Vadla et al., 2023). In this manuscript, they demonstrated that the association of ABT1 with IGHMBP2 significantly increased the ATPase and helicase activity as well as the processivity of IGHMBP2 (changing IGHMBP2 biochemical activity from an inactive to active state).

To understand how a particular mutation impacts molecular function, they examined the six IGHMBP2 mutations in a biochemical context with emphasis on IGHMBP2 activity as an RNA/DNA helicase. They published the biochemical characterization of the IGHMBP2-D565N and IGHMBP2-H924Y mutant proteins (Vadla et al., 2024). For the first time, they demonstrated a correlation between IGHMBP2 biochemical activity associated with the D565N and H924Y mutations and disease severity and pathology in patients and our Ighmbp2 mouse models. Importantly, they show that not all IGHMBP2 mutations are equally amenable to traditional gene therapy applications. The characterization of the Ighmbp2H922Y/H922Y and Ighmbp2D564N/H922Y models was recently published (Ricardez Hernandez et al., 2024). In this manuscript, two important findings were described: 1) early P12 respiratory deficiencies correlate with survival and fitness and 2) motor function deficits are independent of respiratory deficiencies.

Due to the nature of SMARD1 and the phenotypes they have observed in our Ighmbp2 mutant mouse models, they have expanded our studies to include the respiratory circuit, swallowing, the ability to suckle, aspiration and the coordination between respiration and swallowing. These mouse models have provided a valuable resource that has greatly expanded the fields’ knowledge on the function of IGHMBP2 and how IGHMBP2 biochemical function relates to disease development and progression.