jjokerbl

Jonathan
Okerblom
Research Description: 

Alum Jonathan Okerblom earned his PhD with Specialization in Multi-scale Biology in September, 2017.  Approximately 2-3 million years ago, our human ancestors lost the function of CMAH– a gene that remains fully intact in our most closely related species, the bonobos and chimpanzees (1). CMAH codes for a mono-oxygenase that hydroxylates the CMP donor form of the most common sialic acid in mammals called N-acetylneuraminic acid (Neu5Ac), and converts it into N-glycolylneuraminic acid (Neu5Gc). Expression of Neu5Gc varies greatly by tissue type and across different species.  For example, we have found that while the sialic acid content of mouse muscle is ~55% Neu5Gc, western dog muscle is comprised of 1-2% Neu5Gc, which is more similar to humans. This difference in sialic acid content may be an explanation for the difference in muscular dystrophy severity observed between mice, dogs, and humans. In fact, we have previously shown that the loss of Cmah in mice increases the disease severity of the models for Duchenne Muscular Dystrophy (2) and Limb Girdle Muscular Dystrophy type 2D (3). Thus this difference in muscle Neu5Gc content has an as yet unknown effect on muscle function and disease.
(1) Chou HH. et al. PNAS 95; 11751–11756, 1998

(2) Chandrasekharan K. et al. Sci Transl Med. 2;42-54, 2010

(3) Martin PT. et al. Glycobiology. 23;833-43, 2013

Graduate Program: 
Biomedical Sciences
Department(s): 
Medicine and Cellular and Molecular Medicine
Publications: 
PMID: 24789271, 24505439, 28148732, 28423240