Research Areas

A primary thesis underlying all of the work in the Young lab is that multiple PTMs function in concert on single molecules (proteoforms) to encode complex information. This may be considered analogous to a bar code. A natural outcome of this mechanism is the integration of diverse signals. Signals transduced through individual PTMs may be subjected to logical operations and orders of magnitude more information may be persistently stored in a combinatorial register. Such a mechanism of signal integration is widely considered necessary. Although most work to date has explored PTMs for function on a site-by-site basis, strong evidence of connections, interplay, and dependencies abound between PTMs and some combinatorial molecular mechanisms have been demonstrated. Strong evidence supports the concept that histones and other densely modified proteins such as ER, work to store and transduce information combinatorially at the proteoform level. For example, clinical studies of cancer epigenetics show exceptional prognostic/diagnostic value only when multiple PTMs are linked ex post facto. Importantly, it is the pattern of several histone modifications that is able to accurately distinguish outcome. We use cutting edge analytical tools such as top down mass spectrometry, novel chromatography, and computational methods to study otherwise inaccessible aspects of biology. For example such novel subjects include: 1) How multiple post-translational modifications on single protein molecules function in concert and 2) the role of un- or understudied protein variants in gene regulation and disease mechanisms.