In characterizing the effect POFUT2 had on its 50 putative substrates, I became curious if B3GLCT had a redundant role with POFUT2. Surprisingly I found that POFUT2 and B3GLCT were different: while all substrates required POFUT2 for folding and secretion, only a subset of them required B3GLCT. This is particularly significant since mutations in B3GLCT lead to a congenital developmental disorder, Peters Plus Syndrome (PPS), while POFUT2 mice are developmentally lethal. My work dispelled the notion that all 50 potential substrates of B3GLCT are involved in the pathology of PPS. and I identified several key B3GLCT substrates (PMC4318717). Perhaps the most important B3GLCT substrate I helped characterize was ADAMTS9 (PMC5043182). Both B3GLCT mutant mice and ADAMTS9 mutant mice show eye phenotypes similar to those seen in PPS patients. I established that ADAMTS9 was a direct target of B3GLCT using mass spectrometric mapping of glycosylation modifications on ADAMTS9 (see left).

In addition to ADAMTS9, I also contributed to several other mass spectrometry sugar mapping studies, which are in various stages of publication in the Haltiwanger lab.