Michael
Schneider
Education:
B.S. Duke University (2011)
Ph.D. Stony Brook University (2017)
Current Position:
8th Year MSTP
4th Year Medical Student
Advisor:
Dr. Robert Haltiwanger
Graduate Program:
Pharmacology
Research Interest:
Notch is a cell-surface receptor that controls cell fate decisions and is regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF repeats with O-fucose and is essential for Notch signaling. Constitutive activation of Notch signaling has been associated with a variety of human malignancies. Therefore, tools for inhibiting Notch activity are being developed as cancer therapeutics. Towards this end, we screened L-fucose analogs for their effects on Notch signaling. Two analogs, 6-alkynyl and 6-alkenyl fucose, were substrates of Pofut1 and were incorporated directly into Notch EGF repeats in cells. Both analogs were potent inhibitors of binding to and activation of Notch1 by Notch ligands Dll1 and Dll4, but not by Jag1.
Publications:
Hubmacher D, Schneider M, Berardinelli SJ, Takeuchi H, Willard B, Reinhardt DP, Haltiwanger RS, Apte SS Scientific Reports. 2017, 0:7 Unusual life cycle and impact on microfibril assembly of ADAMTS17, a secreted metalloprotease mutated genetic eye disease.
Schneider M, Al-Shareffi E, Haltiwanger RS Glycobiology. 2017, 27(7):601-618 Biological functions of fucose in mammals.
Schneider M, Kumar V, Nordstrøm LU, Feng L, Takeuchi H, Hao H, Luca VC, Garcia KC, Stanley P, Wu P, Haltiwanger RS Nature Chemical Biology. 2018, 14(1):65-71 Inhibition of Delta-induced Notch signaling using fucose analogs.
Takeuchi H, Wong D, Schneider M, Freeze HH, Takeuchi M, Berardinelli SJ, Ito A, Lee H, Nelson SF, Haltiwanger RS Glycobiology. 2018, 28(5):276-283 Variant in human POFUT1 reduces enzymatic activity and likely causes a recessive microcephaly, global developmental delay with cardiac and vascular features.
Takeuchi H*, Schneider M*, Williamson DB, Ito A, Takeuchi M, Hanford PA, Haltiwanger RS. In Revision. Identification of two novel protein O-glycosyltransferases that modify sites distinct from those modified by POGLUT1 and affect Notch signaling and trafficking.
