Derek A. Applewhite
Assistant Professor of Biology
3203 SE Woodstock Blvd.
Portland, OR 97202
The central goal of my research—To understand the regulation of the cytoskeleton.
Just as we have bones and muscles that give our bodies shape and allow us to move, cells have analogous structures known as the cytoskeleton. The cytoskeleton is composed of three filament networks, the actin, microtubule, and intermediate filament cytoskeletons. All three networks are composed of polymers that polymerize to form larger networks. It is these networks, that are dynamic and highly regulated, that give cells their shape and allow them to move. The cytoskeleton is therefore critical to the shape change or morphogenesis cells undergo during development, immune functions, the path finding that developing neurons undergo when establishing connections, and in cases where the cytoskeletal machinery works aberrantly, metastasis during tumorgenesis.
Why Drosophila (fruit flies) and Drosophila cells? My research uses both Drosophila derived cells and the flies themselves. Drosophila cells are easily cultured, amenable to high resolution imaging, and are exquisitely sensitive to RNAi depletion. The cells can be manipulated through the expression of exogenous proteins and by the use of pharmacological inhibitors to probe the function of the cytoskeleton in a variety of ways. My research also uses the developing Drosophila embryo, taking advantage of the powerful genetics this model organism represents to answer basic questions of how the cytoskeleton is regulated, and to study cell motility in the context of a developing organism.
Key questions my research is addressing...
How does class of molecules known as actin-microtubule cross-linkers function in regulating the cytoskeleton?
How is actomyosin contractility regulated during interphase?
How can we test current models of cytoskeletal regulation in developing Drosophila embryos?
The actin-microtubule cross-linking activity of Drosophila Short stop is regulated by intramolecular inhibition.
Applewhite DA, Grode KD, Duncan MC, Rogers SL.
Mol Biol Cell. 2013 Sep;24(18):2885-93. doi: 10.1091/mbc.E12-11-0798. Epub 2013 Jul 24.
PMID: 23885120 [PubMed - in process]
The spectraplakin Short stop is an actin-microtubule cross-linker that contributes to organization of the microtubule network.
Applewhite DA, Grode KD, Keller D, Zadeh AD, Slep KC, Rogers SL.
Mol Biol Cell. 2010 May 15;21(10):1714-24. doi: 10.1091/mbc.E10-01-0011. Epub 2010 Mar 24. Erratum in: Mol Biol Cell. 2010 Jun 15;21(12):2097. Zadeh, Alireza [corrected to Zadeh, Alireza Dehghani].
PMID: 20335501 [PubMed - indexed for MEDLINE]
Ena/VASP proteins have an anti-capping independent function in filopodia formation.
Applewhite DA, Barzik M, Kojima S, Svitkina TM, Gertler FB, Borisy GG.
Mol Biol Cell. 2007 Jul;18(7):2579-91. Epub 2007 May 2.
PMID: 17475772 [PubMed - indexed for MEDLINE]
Responsive microtubule dynamics promote cell invasion by Trypanosoma cruzi.
Tyler KM, Luxton GW, Applewhite DA, Murphy SC, Engman DM.
Cell Microbiol. 2005 Nov;7(11):1579-91.
PMID: 16207245 [PubMed - indexed for MEDLINE]
Lamellipodial versus filopodial mode of the actin nanomachinery: pivotal role of the filament barbed end.
Mejillano MR, Kojima S, Applewhite DA, Gertler FB, Svitkina TM, Borisy GG.
Cell. 2004 Aug 6;118(3):363-73.
PMID: 15294161 [PubMed - indexed for MEDLINE]