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Scholarly Interest Report
         
Laura Segatori
Associate Professor
Associate Professor in Chemical and Biomolecular Engineering
 
e-mail:segatori@rice.edu
 
  • Ph.D. Chemical Engineering (2005) University of Texas at Austin, Austin, TX
  • B.S. Industrial Biotechnology (2000) University of Bologna, Italy
 
Primary Department
   Department of Chemical and Biomolecular Engineering
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Department Affiliations
 
  • Department of BioSciences
  • Department of Bioengineering
  • Institute of Biosciences and Bioengineering
  • Smalley Institute for Nanoscale Science and Technology
  •  
    Websites
     Segatori - Research group
     
    Research Areas
     Biotechnology; Cell and Protein Engineering; Synthetic Biology; Cellular Protein Folding; Protein aggregation; Proteasomal degradation; Autophagy
     

    Engineering Cellular Quality Control Systems

     

    Drawing on my interdisciplinary training, I combine principles and tools from engineering and science to elucidate biological systems. My research group applies cell and protein engineering tools and classical biochemistry and molecular biology methods to understand and manipulate cellular quality control mechanisms that underlie the development of human diseases. Specifically, we have developed novel biotechnologies to manipulate the innate cellular capacity to i) promote protein folding and processing and ii) degrade toxic cellular waste. Our ultimate goal is to restore cellular homeostasis for applications in biomedicine and bioengineering.


    Research in my group is highly interdisciplinary as it focuses on:


    1) biological and chemical strategies to study and treat diseases of proteostasis deficiency


    2) synthetic biology tools to engineer cellular degradation pathways


    3) bionanotechnology to manipulate cellular clearance mechanisms

     
    Teaching Areas
     Biomolecular Engineering; Protein Engineering
     
    Selected Publications
     Refereed articles
     

    Segatori L "Impairment of Homeostasis in Lysosomal Storage Disorders." IUBMB Life, 66: 472477.

     
     

    Song W, Soo Lee S, Savini M, Popp L, Colvin VL, Segatori L. "Ceria Nanoparticles Stabilized by Organic Surface Coatings Activate the Lysosome-Autophagy System and Enhance Autophagic Clearance." ACS Nano, 8: 10328-42.

     
     

    Song, W, Wang F, Lofti P, Sardiello M, Segatori L "2-hydroxypropyl-β-Cyclodextrin promotes TFEB-mediated activation of autophagy: implications for therapy." The Journal of Biological Chemistry, 289: 10211 -22.

     
     

    Wang J, Liu KW, Segatori L, Biswal SL. Lipid bilayer phase transformations detected using microcantilevers. J Phys Chem B. 2014 Jan 9;118(1):171-8. doi: 10.1021/jp4095112

     
     

    Wang J, Morton MJ, Elliott CT, Karoonuthaisiri N, Segatori L, Biswal SL. Rapid detection of pathogenic bacteria and screening of phage-derived peptides using microcantilevers. Anal Chem 2014 Jan 21.doi: 10.1021/ac403437x

     
     

    Wang J, Segatori L, Biswal SL "Probing the association of triblock copolymer with supported lipid membranes using microcantilevers.." Soft Matter, 10: 6417-24.

     
     

    doi:10.1038/ncomms4612

     
     

    Kilpatrick K, Novoa JA, Hancock T, Guerriero CJ, Wipf P, Brodsky JL,Segatori L. Chemical induction of Hsp70 reduces alpha-synuclein aggregation in neuroglioma cells. ACS Chem Biol. 2013. 8 (7), 1460-1468. doi: 10.1021/cb400017h.

     
     

    Lee SS, Song W, Cho M, Puppala HL, Nguyen P, Zhu H, Segatori L, and Colvin V. “Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal diameter and surface coating”. ACS Nano Sept 2013 doi: 10.1021/nn4026806.

     
     

    Mauri V, Segatori L, Sardiello, M. A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells. PLoS ONE. July 2013. 8(6):e68060. doi: 10.1371/journal.pone.0068060.

     
     

    Song W, Wang F, Savini M, Ake A, Di Ronza A, Sardiello M, Segatori L. TFEB regulates lysosomal proteostasis. Human Molecular Genetics 2013.  May 15;22(10):1994-2009. doi: 10.1093/hmg/ddt052. Epub 2013 Feb 7. Journal cover.

     
     

    Wang F and Segatori L. Remodeling the proteostasis network to rescue glucocerebrosidase variants by inhibiting  ER-associated degradation and enhancing ER folding. PLoS ONE. Apr 2013 19;8(4):e61418. doi: 10.1371/journal.pone.0061418.

     
     

    Wang F, Lofti P, Sardiello M, Segatori L*. 2-hydroxypropyl-β-Cyclodextrin promotes TFEB-mediated activation of autophagy: implications for therapy. J Biol Chem (in revision).

     
     

    Wang F, Lofti P, Sardiello M, Segatori L. 2-hydroxypropyl-β-Cyclodextrin promotes TFEB-mediated activation of autophagy: implications for therapy. J Biol Chem.

     
     

    Zhao W, Bonem M, McWhite C, Silberg JJ, Segatori L. The Deg-On system: a mammalian synthetic gene circuit to quantify proteasomal degradation. Nature Communications. In revision

     
     

    Cook NP, Kilpatrick K, Segatori L, Marti AA. Detection of a-synuclein amyloidogenic aggregates in vitro and in cells using light-switching dipyridophenazine ruthenium(II) complexes. Journal of the American Chemical Society 2012 Dec 26;134(51):20776-82.

     
     

    Kothawala A, Kilpatrick K, Novoa JA, Segatori L. Quantitative analysis of alpha-synuclein solubility in living cells using split GFP complementation. PLoS One 2012;7(8):e43505. doi: 10.1371/journal.pone.0043505.

     
     

    Mathieu JM, Wang F, Segatori L, Alvarez PJ. Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase. Biotechnology and Bioengineering 2012 Sep;109(9):2409-15. doi: 10.1002/bit.24506.

     
     

    Wang J, AlMakhaita M Biswal S, Segatori L. Sensitive detection of TNT using competition assay on quartz crystal microbalance. Biosensors and Bioelectronics 2012. 3:115. doi:10.4172/2155-6210.1000115

     
     Articles
     

    Wang F, Chou A, Segatori L. Lacidipine remodels protein folding and Ca2+ homeostasis in Gaucher's disease patient-derived fibroblasts: a novel mechanism for mutant glucocerebrosidase proteostasis. Chemistry and Biology. 2011 Jun 24;18(6):766-76.

     
     

    Wang F, Song W, Brancati G, Segatori L. Inhibition of Endoplasmic Reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases.  Journal of Biological Chemistry 2011 Dec 16;286(50):43454-64.

     
     

    Wang F, Agnello G, Sotolongo N, and Segatori L. Ca2+ homeostasis modulation enhances the amenability of L444P fglucosylcerebrosidase to proteostasis regulation in patient-derived fibroblasts. ACS Chem Biol. 2010 Nov 2.

     
     

    Arredondo S, Segatori L, Gilbert HF, Georgiou G. De novo design and evolution of artificial disulfide isomerase enzymes analogous to the bacterial DsbC. J Biol Chem. 2008 Nov 14;283(46):31469-76.

     
     

    Mu TW, Ong DS, Wang YJ, Balch WE, Yates JR 3rd, Segatori L, Kelly JW. Chemical and biological approaches synergize to ameliorate protein-folding diseases. Cell. 2008 Sep 5;134(5):769-81.

     
     

    Georgiou G, Segatori L. Preparative expression of secreted proteins in bacteria: status report and future prospects. Curr Opin Biotechnol. 2005 Oct;16(5):538-45. Review.


     
     

    Segatori L, Murphy L, Arredondo S, Kadokura H, Gilbert H, Beckwith J, Georgiou G. Conserved role of the linker alpha-helix of the bacterial disulfide isomerase DsbC in the avoidance of misoxidation by DsbB. J Biol Chem. 2006 Feb 24;281(8):4911-9.

     
     

    Segatori L, Paukstelis PJ, Gilbert HF, Georgiou G. Engineered DsbC chimeras catalyze both protein oxidation and disulfide-bond isomerization in Escherichia coli: Reconciling two competing pathways.  Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10018-23.

     
     

    Zhang M, Monzingo AF, Segatori L, Georgiou G, Robertus JD. Structure of DsbC from Haemophilus influenzae. Acta Crystallogr D Biol Crystallogr. 2004 Sep;60(Pt 9):1512-8.

     
    Presentations
     Conference Committee Member
     

    Biomedical Engineering Society Meeting. Track Chair: Cellular and Molecular Engineering.

     
     Invited Papers
     

    “Nanoparticles as autophagy activators”  American Chemical Society Annual Meeting .April, 2013. New Orleans, LA.

     
     

    "Novel technologies for the detection and cellular degradation of misfolded proteins" Biochemical and Molecular Engineering XVII. Seattle, WA. June 2011.

     
     

    "Novel technologies for the detection of misfolded toxic a-synuclein" Midwest ER Stress and Chaperones. Chicago, IL. January 2011.

     
     

    “Ca2+ Homeostasis and Proteostasis Modulation Synergize to Rescue the Folding of Unstable Secretory Proteins ” American Institute of Chemical Engineering. Salt Lake City. November 2010.

     
     

    Wang F and Segatori L. "Modulation of Ca2+ homeostasis and proteostasis for lysosomal storage disease therapeutics" Biomedical Engineering Society Meeting. Austin, TX. Oct 2010

     
     

    Kothawala A and Segatori L. "Novel technologies for the detection of a-synuclein misfolded toxic species". American Institute of Chemical Engineering. Salt Lake City, UT. Nov 2010

     
     

    "Restoring Ca2+ homeostasis promotes a wild-type like ER folding environment amenable to proteostasis regulation in Gaucher's disease" Midwest ER Stress and Chaperones. Chicago, IL. Jan 2010

     
     

    Wang J, Biswal SL, and Segatori L. " Sensitive TNT detection using QCM via competition assay" American Institute of Chemical Engineering. Salt Lake City, UT. Nov 2010

     
     

    “The Deg-On System: Generation of a Cell-Based Assay for the Screening of Proteasome Activators” American Institute of Chemical Engineering. Salt Lake City, UT. November 2010.

     
     

    "Pharmacologic enhancement of the chemistry and biology of cellular protein folding." American Institute of Chemical Engineering. Salt Lake City, UT. November 2007.

     
     Invited Talks
     

    “Engineering the proteostasis network for applications in biomedicine and nanotechnology” Rice University: Department of Biochemistry and Cell Biology  Research Symposium and Retreat. August 24, 2013. Houston, TX.

     
     

    “Nanoparticles as autophagy activators” International Conference on Biomolecular Engineering: Society for Biological Engineering. January 16, 2013. Fort Lauderdale, FL.

     
     

     “Remodeling the proteostasis network to enhance cellular folding” Pfizer: Rare Disease Research Unit. September 7, 2012. Boston, MA.

     
     

    "Ca2+ homeostasis and proteostasis regulation synergize to rescue glucocerebrosidase folding in Gaucher’s disease patient-derived fibroblasts" Gordon Research Conference: Lysosomal diseases. Galveston TX, January 2011.

     
     

    "Ca2+ homeostasis and proteostasis modulation sinergyze to ameliorate lysosomal storage diseases". Texas Protein Folding Meeting. Houston, TX. March 2010.

     
     

    "Protein folding quality control system profiling for the design of therpeutics". The Keck Centre for Interdisciplinary Bioscience Training, Gulf Coast Consortia, Houston, TX. October 2009.

     
     Keynote Speaker
     

    "Understanding and ameliorating loss-of-function protein misfolding diseases". The Houston Society for Engineering in Medicine and Biology. Houston, TX. March 2009.

     
     Posters
     

    "“Sensitive detection of proteasomal degradation using orthogonal gene circuits”." Synthetic Biology, Engineering, Evolution & Design, Manhattan Beach, CA. (July 2014)

     
     

    Wang F and Segatori L. "Remodeling protein folding and Ca2+ homeostasis in Gaucher's disease patient-derived fibroblasts: a novel mechanism for mutant glucocerebrosidase proteostasis" MIdwest ER Stress and Chaperones. Chicago, IL. Jan 2011.

     
     

    Kilpatrick K, Kothawala A, and Segatori L. Enhancing the degradation of a-synuclein oligomeric toxic species. Midwest ER Stress and Chaperones. Chicago, IL. January 2010.

     
     

    Kilpatrick K and Segatori L. "Modulating the cellular accumulation of toxic misfolded a-synuclein". Biomedical Engineering Society Meeting. Austin, TX. Oct 2010

     
     

    Wang F, Sotolongo, Diaz A, and Segatori L. "Novel approaches for the treatment of Gaucher's disease". The Houston Society for Engineering in Medicine and Biology. Houston, TX. March 2009

     
     

    "Toward loss-of-function protein misfolding disease therapeutics. A focus on Gaucher's disease". American Society for Biological Engineering. San Diego, January 2007.

     
     Seminar Speaker
     

    “Engineering the proteostasis network to enhance cellular clearance” The Ohio State University: Department of Chemical and Biomolecular Engineering. September 5, 2013. Columbus, OH.  

     
     

    Invited Departmental Seminar: “Engineering the proteostasis network to enhance cellular clearance” University of Houston: Department of Chemical and Biomolecular Engineering. September 10, 2013. Houston, TX.

     
     

    “Engineering the proteostasis network to enhance cellular clearance” University of Texas Health Science Center: Department of Integrative Biology and Pharmacology. October 14, 2013. Houston, TX.

     
     

    “Engineering the proteostasis network to enhance cellular clearance” University of California, Berkeley: Department of Chemical and Biomolecular Engineering. December 11, 2013. Berkeley, CA.

     
     

    “Reprogramming the proteostasis network to enhance clearance of cellular toxic material” Tulane University: Department of Chemical and Biomolecular Engineering. October 26, 2012. New Orleans, LA.

     
     

    “Reprogramming the proteostasis network to enhance clearance of cellular toxic material” University of Pittsburgh: Department of Biological Sciences. October 29, 2012. Pittsburgh, PA.

     
     

    “Engineering the cellular forlding quality control for therapeutic applications”, Tsinghua University. Beijing, China. May 2010.

     
     

    "Engineering the cellular folding quality control for therapeutic applications" Tianjin University. Tianjin, China. May 2010.


     
     

    “Chemical and Biological approaches for the design of protein folding disease therapeutics”, The University of Texas at Houston. Microbiology and Molecular Genetics. Houston, TX. March 4, 2010.

     
     

    “Novel therapeutic strategies for protein misfolding diseases”, Centro Interdipartimentale per le  Biotecnologie  Applicate. Universita’ di Palermo, Italy. June 2010.

     
     

    “Chemical and Biological approaches for the design of protein folding disease therapeutics”, University of Puerto Rico. Mayaguez, PR. August 2009.

     
     Session Chair
     

    "Bionanotechnology." American Chemistry Society Annual Meeting, Dallas, TX. (March 2014)

     
     

    "Protein Engineering I - Therapeutics." American Institute of Chemical Engineering Annual Meeting, Atlanta, GA. (November 2014)

     
     

    Cellular Engineering. Biomedical Engineering Society Meeting. Austin, TX. Oct 2010

     
     

    Poster Session. Society of Biological Engineering. Santa Barbara, CA. Jan 2010

     
     

    Tissue Engineered Models for Drug Discovery. Biomedical Engineering Society Meeting. Austin, TX. Oct 2010

     
     

    Protein Engineering. American Institute of Chemical Engineering. Philadelphia, PA. Nov 2008

     
     Workshops
     

    "High throughput screenings for protein misfolding disease therapeutics" Gulf Coast Consortium for Chemcial Genomics and Bioinformatics Workshop. University of Texas Health Science Centre. Houston, TX. October 2008.

     
    Editorial Positions
     Other, Protein Science. (2010 - 2010)

     Other, Journal of Biomedicine and Biotechnology. (2010 - 2010)

     Other, Current Protein and Peptide Science. (2010 - 2010)

     Other, PLOS. (2010 - 2010)

     Other, Applied Biochemistry and Biotechnology. (2010 - 2010)

     Other, Annals of Biomedical Engineering. (2010 - 2010)

    Supervised Theses & Dissertations
     Janping Chen, PhD Molecular basis of gene dosage sensitivity. (2008) (Thesis Committee Member)

     Venetia Rigou, Master Kinetic and statistical approaches in metabolic network. (2008) (Thesis Committee Member)

     Xi Zhang, PhD Specificity in the druggable kinome: molecular basis and its applications. (2008) (Thesis Committee Member)

     Abishek Muraka, PhD Metabolic flux analysis of fermentative carbon metabolism. (2008) (Thesis Committee Member)

     Wejia Xie, Master Assembling magnetic colloidal paricles in microfluidic. (2009) (Thesis Committee Member)

     Nashiely Martinez, PhD Insights into peroxisome matrix protein import ans IBA metabolisms through analysis of IBA-response mutants. (2009) (Thesis Committee Member)

     Peng Zhai, PhD Escort protein regulation of the human mitochondrial molecular chaperone mtHsp70. (2010) (Thesis Committee Member)

     Jacques Mathieu, PhD Strategies for the Mitigation of Oxysterol-Induced Cytotoxicity. (2011) (Thesis Committee Member)

     John Park, MS Engineering Escherichia coli for the production of polyketide-based platform chemicals. (2011) (Thesis Committee Member)

     Kaiwei Liu, PhD Studying the Interactions of Biomacromolecular Assemblies with Surfaces Using the Microcantilever Sensor and Quartz Crystal Microbalance. (2011) (Thesis Committee Member)

     Ruiqiang San, MS Improved understanding of apoptosis and metabolism in Chinese Hamster Ovary cell culture. (2011) (Thesis Committee Member)

     Clementina Dellomonaco, PhD Novel approaches for the production of fuels and chemicals in Escherichia coli. (2011) (Thesis Committee Member)

     Fan Wang, PhD Modulating Protein Homeostasis to Ameliorate Lysosomal Storage Disorders. (2012) (Thesis Director)

     Wensi Song, PhD Modulating the Lysosome-Autophagy System to Restore Homeostasis in in vitro Model Systems of Lysosomal Storage Disorders. (2014) (Thesis Director)

     Jinghui Wang, PhD Characterization and Application of Immobilized Macromolecules using Microcantilever and QCM Sensors. (2014) (Thesis Director)

    Awards, Prizes, & Fellowships
     Hamill Innovation Award, Institute of Bioscience and Bioengineering. Rice University. , nstitute of Bioscience and Bioengineering. Rice University. (2013)

     NSF CAREER Award, NSF (2013)

     Sigma Xi, The Scientific Research Society, Sigma Xi, The Scientific Research Society (2012)

     Virginia and L. E. Simmons Family Foundation Award , Virginia and L. E. Simmons Family Foundation (2011)

     Medical Innovation Award, Institute of Bioscience and Bioengineering. Rice University. (2011)

     Medical Innovation Award, Institute of Bioscience and Bioengineering (2010)

     Hamill Innovation Award, Institute of Bioscience and Bioengineering (2009)

    Positions Held
     Member - Biomedical Engineering Society . (2010 - 2010)

     Member - American Chemical Society. (2010 - 2010)

     Member - Society of Biological Engineering. (2010 - 2010)

     Member - American Institute of Chemical Engineering. (2010 - 2010)