Scholars@Duke
Chris Freel

Chris Freel

Assoc VP, Research
Duke University
christopher.freel@duke.edu
Office for Research & Innovation, Box 90037, Durham, NC 27708
121 Allen Building, Box 90037, 421 Chapel Drive, Durham, NC 27708

Selected Publications

The deubiquitinating enzyme DUBAI stabilizes DIAP1 to suppress Drosophila apoptosis.

Journal Article Cell Death Differ · April 2014 Deubiquitinating enzymes (DUBs) counteract ubiquitin ligases to modulate the ubiquitination and stability of target signaling molecules. In Drosophila, the ubiquitin-proteasome system has a key role in the regulation of apoptosis, most notably, by controll ... Full text Link to item Cite

Cellular mechanisms controlling caspase activation and function.

Journal Article Cold Spring Harbor perspectives in biology · June 2013 Caspases are the primary drivers of apoptotic cell death, cleaving cellular proteins that are critical for dismantling the dying cell. Initially translated as inactive zymogenic precursors, caspases are activated in response to a variety of cell death stim ... Full text Cite

Cellular mechanisms controlling caspase activation and function

Journal Article Cold Spring Harbor Perspectives in Medicine · June 1, 2013 Caspases are the primary drivers of apoptotic cell death, cleaving cellular proteins that are critical for dismantling the dying cell. Initially translated as inactive zymogenic precursors, caspases are activated in response to a variety of cell death stim ... Cite

Rsk-mediated phosphorylation and 14-3-3ɛ binding of Apaf-1 suppresses cytochrome c-induced apoptosis.

Journal Article The EMBO journal · March 2012 Many pro-apoptotic signals trigger mitochondrial cytochrome c release, leading to caspase activation and ultimate cellular breakdown. Cell survival pathways, including the mitogen-activated protein kinase (MAPK) cascade, promote cell viability by impeding ... Full text Cite

Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death.

Journal Article Cell death and differentiation · October 2011 In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophil ... Full text Open Access Cite

A biotin switch-based proteomics approach identifies 14-3-3ζ as a target of Sirt1 in the metabolic regulation of caspase-2.

Journal Article Mol Cell · September 2, 2011 While lysine acetylation in the nucleus is well characterized, comparatively little is known about its significance in cytoplasmic signaling. Here we show that inhibition of the Sirt1 deacetylase, which is primarily cytoplasmic in cancer cell lines, sensit ... Full text Link to item Cite

Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability.

Journal Article Mol Biol Cell · April 15, 2011 Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as ... Full text Link to item Cite

Metabolic regulation of Drosophila apoptosis through inhibitory phosphorylation of Dronc.

Journal Article The EMBO journal · September 2010 Apoptosis ensures tissue homeostasis in response to developmental cues or cellular damage. Recently reported genome-wide RNAi screens have suggested that several metabolic regulators can modulate caspase activation in Drosophila. Here, we establish a previ ... Full text Cite

Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism.

Journal Article Molecular biology of the cell · August 2010 Vertebrate eggs are arrested at Metaphase II by Emi2, the meiotic anaphase-promoting complex/cyclosome (APC/C) inhibitor. Although the importance of Emi2 during oocyte maturation has been widely recognized and its regulation extensively studied, its mechan ... Full text Open Access Cite

Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring.

Journal Article Cell death and differentiation · January 2010 Factors influencing apoptosis of vertebrate eggs and early embryos have been studied in cell-free systems and in intact embryos by analyzing individual apoptotic regulators or caspase activation in static samples. A novel method for monitoring caspase acti ... Full text Open Access Cite

Restraint of apoptosis during mitosis through interdomain phosphorylation of caspase-2.

Journal Article EMBO J · October 21, 2009 The apoptotic initiator caspase-2 has been implicated in oocyte death, in DNA damage- and heat shock-induced death, and in mitotic catastrophe. We show here that the mitosis-promoting kinase, cdk1-cyclin B1, suppresses apoptosis upstream of mitochondrial c ... Full text Link to item Cite

Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2.

Journal Article Developmental cell · June 2009 Xenopus oocyte death is partly controlled by the apoptotic initiator caspase-2 (C2). We reported previously that oocyte nutrient depletion activates C2 upstream of mitochondrial cytochrome c release. Conversely, nutrient-replete oocytes inhibit C2 via S135 ... Full text Cite

PP1-mediated dephosphorylation of phosphoproteins at mitotic exit is controlled by inhibitor-1 and PP1 phosphorylation.

Journal Article Nature cell biology · May 2009 Loss of cell division cycle 2 (Cdc2, also known as Cdk1) activity after cyclin B degradation is necessary, but not sufficient, for mitotic exit. Proteins phosphorylated by Cdc2 and downstream mitotic kinases must be dephosphorylated. We report here that pr ... Full text Cite

Cdc2 and Mos regulate Emi2 stability to promote the meiosis I-meiosis II transition.

Journal Article Molecular biology of the cell · August 2008 The transition of oocytes from meiosis I (MI) to meiosis II (MII) requires partial cyclin B degradation to allow MI exit without S phase entry. Rapid reaccumulation of cyclin B allows direct progression into MII, producing a cytostatic factor (CSF)-arreste ... Full text Cite

Aven-dependent activation of ATM following DNA damage.

Journal Article Curr Biol · July 8, 2008 BACKGROUND: In response to DNA damage, cells undergo either cell-cycle arrest or apoptosis, depending on the extent of damage and the cell's capacity for DNA repair. Cell-cycle arrest induced by double-stranded DNA breaks depends on activation of the ataxi ... Full text Link to item Cite

Mitochondrial localization of Reaper to promote inhibitors of apoptosis protein degradation conferred by GH3 domain-lipid interactions.

Journal Article J Biol Chem · January 4, 2008 Morphological hallmarks of apoptosis result from activation of the caspase family of cysteine proteases, which are opposed by a pro-survival family of inhibitors of apoptosis proteins (IAPs). In Drosophila, disruption of IAP function by Reaper, HID, and Gr ... Full text Link to item Cite

Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 2007 Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting t ... Full text Open Access Cite

Differential susceptibility of yeast S and M phase CDK complexes to inhibitory tyrosine phosphorylation.

Journal Article Curr Biol · July 17, 2007 BACKGROUND: Several checkpoint pathways employ Wee1-mediated inhibitory tyrosine phosphorylation of cyclin-dependent kinases (CDKs) to restrain cell-cycle progression. Whereas in vertebrates this strategy can delay both DNA replication and mitosis, in yeas ... Full text Link to item Cite

A role for Cdc2- and PP2A-mediated regulation of Emi2 in the maintenance of CSF arrest.

Journal Article Current biology : CB · February 2007 BackgroundVertebrate oocytes are arrested in metaphase II of meiosis prior to fertilization by cytostatic factor (CSF). CSF enforces a cell-cycle arrest by inhibiting the anaphase-promoting complex (APC), an E3 ubiquitin ligase that targets Cyclin ... Full text Cite

Role for the PP2A/B56delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis.

Journal Article Cell · November 17, 2006 DNA-responsive checkpoints prevent cell-cycle progression following DNA damage or replication inhibition. The mitotic activator Cdc25 is suppressed by checkpoints through inhibitory phosphorylation at Ser287 (Xenopus numbering) and docking of 14-3-3. Ser28 ... Full text Link to item Cite

A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25.

Journal Article Mol Biol Cell · April 2006 The Cdc25 phosphatase promotes entry into mitosis through the removal of inhibitory phosphorylations on the Cdc2 subunit of the Cdc2/CyclinB complex. During interphase, or after DNA damage, Cdc25 is suppressed by phosphorylation at Ser287 (Xenopus numberin ... Full text Link to item Cite

Distribution, spherical structure and predicted Mie scattering of multilamellar bodies in human age-related nuclear cataracts.

Journal Article Experimental eye research · October 2004 PurposeTo characterize multilamellar bodies (MLBs), determine their distribution along the optic axis and predict their potential Mie scattering within human age-related nuclear cataracts. Previous studies restricted to the equatorial plane have s ... Full text Cite

Simultaneous stretching and contraction of stress fibers in vivo.

Journal Article Molecular biology of the cell · July 2004 To study the dynamics of stress fiber components in cultured fibroblasts, we expressed alpha-actinin and the myosin II regulatory myosin light chain (MLC) as fusion proteins with green fluorescent protein. Myosin activation was stimulated by treatment with ... Full text Cite

Mie light scattering analysis of human age-related nuclear cataracts

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2004 Link to item Cite

Cataract formation in a strain of rats selected for high oxidative stress

Journal Article Experimental Eye Research · 2004 Cite

Ultrastructural characterization and Fourier analysis of fiber cell cytoplasm in the hyperbaric oxygen treated guinea pig lens opacification model.

Journal Article Experimental eye research · April 2003 The structural characteristics of differentiated fiber cells in control and hyperbaric oxygen (HBO)-treated guinea pig lenses were examined by transmission electron microscopy (TEM). Emphasis was placed on cell damage, membrane integrity, and cytoplasmic t ... Full text Cite

Analysis of nuclear fiber cell compaction in transparent and cataractous diabetic human lenses by scanning electron microscopy

Journal Article BMC Ophthalmology · January 6, 2003 Background: Compaction of human ocular lens fiber cells as a function of both aging and cataractogenesis has been demonstrated previously using scanning electron microscopy. The purpose of this investigation is to quantify morphological differences in the ... Full text Cite

Fourier analysis of cytoplasmic texture in nuclear fiber cells from transparent and cataractous human and animal lenses.

Journal Article Experimental eye research · June 2002 Comparisons were made of the cytoplasmic textures in electron microscope images of nuclear fiber cells from a variety of human and animal lenses. The goals were to establish the optimal conditions for quantifying the textural features and for relating the ... Full text Cite

Random distribution of multilannellar bodies in human age-related nuclear cataracts

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · May 1, 2002 Link to item Cite

Multilamellar bodies as potential scattering particles in human age-related nuclear cataracts.

Journal Article Molecular vision · June 2001 PurposeTo characterize within human age-related nuclear cataracts rare spherical objects covered by multiple membranes, termed multilamellar bodies (MLBs).MethodsAdult human normal, transparent lenses were obtained from eye bank donors an ... Cite

Structural evidence of human nuclear fiber compaction as a function of ageing and cataractogenesis.

Journal Article Experimental eye research · March 2001 This study was conducted to quantify structural change associated with human nuclear fiber compaction as a function of ageing and nuclear cataract formation. Normal donor lenses in three age ranges, young (15--25 years), middle-aged (36--46 years) and aged ... Full text Cite