Sarah Domnitz

Department: Physiology and Biophysics
Year Entered: 2004
Prior Degrees: BS, University of Michigan Ann Arbor, 2001

Research Interests:
Proper cellular function relies on maintenance of microtubules, an essential component of the cell cytoskeleton. Microtubules are inherently dynamic; they stochastically transition between periods of growth and shortening. However, the kinetics of microtubule growth and shrinkage are tightly regulated in cells. While numerous regulators of microtubule dynamics have been identified, very little is known about how the functions of these regulators are controlled to accomplish cellular processes. I study how cells coordinate the expression and localization of the microtubule regulators mitotic centromere-associated kinesin (MCAK) and End Binding protein 1 (EB1). MCAK destabilizes microtubules by removing tubulin dimers from microtubule ends. EB1 associates with polymerizing microtubule tips and may interact or compete with microtubule regulators such as MCAK. I use molecular biology, cell
culture, and microscopy to manipulate the levels of these two proteins in cells and measure the various adjustments the cell makes to maintain the microtubule array.

I became interested in the Molecular Medicine program because I wanted to link my knowledge of basic cell function more directly to the medical field. My career goal is to apply my knowledge of basic cell science to work in public health. I think the Molecular Medicine training will help me make this transition.

Publications:
A kinesin-13 mutant catalytically depolymerizes microtubules in ADP. Wagenbach M, Domnitz S, Wordeman L, Cooper J. J Cell Biol. 2008 Nov 17;183(4):617-23. Epub 2008 Nov 10.

In vitro and in vivo analysis of microtubule-destabilizing kinesins. Stumpff J, Cooper J, Domnitz S, Moore AT, Rankin KE, Wagenbach M, Wordeman L. Methods Mol Biol. 2007;392:37-49.

Kinetics of cerebral amyloid angiopathy progression in a transgenic mouse model of Alzheimer disease. Robbins EM, Betensky RA, Domnitz SB, Purcell SM, Garcia-Alloza M, Greenberg C, Rebeck GW, Hyman BT, Greenberg SM, Frosch MP, Bacskai BJ. J Neurosci. 2006 Jan 11;26(2):365-71.

Progression of cerebral amyloid angiopathy in transgenic mouse models of Alzheimer disease. Domnitz SB, Robbins EM, Hoang AW, Garcia-Alloza M, Hyman BT, Rebeck GW, Greenberg SM, Bacskai BJ, Frosch MP. J Neuropathol Exp Neurol. 2005 Jul;64(7):588-94.

The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A, Moir RD, Domnitz SB, Frosch MP, Windisch M, Kovacs DM. Neuron. 2004 Oct 14;44(2):227-38.