Nichola C. Garbett, Ph.D.

Education:

B.Sc. (Hons.), Chemistry, University of Kent at Canterbury, Canterbury, England, 1996
Ph.D., Chemistry, University of Kent at Canterbury, Canterbury, England, 2000
Postdoctoral Fellowship, University of Mississippi Medical Center, Jackson MS, 2001
Postdoctoral Fellowship, University of Mississippi, Oxford MS, 2003
Postdoctoral Fellowship, University of Alabama at Birmingham, Birmingham AL, 2004
Postdoctoral Fellowship, University of Louisville, Louisville KY, 2007

Curriculum Vitae

Current Positions:

Assistant Professor, Department of Medicine, University of Louisville School of Medicine
Member, James Graham Brown Cancer Center
Assistant Director, Biophysical Core Facility, James Graham Brown Cancer Center
Associate Member, Department of Biochemistry, University of Louisville School of Medicine

Contact Information:

Clinical Translational Research Building, Room 206
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone 502-852-3479
Fax 502-852-7979
Email: nichola.garbett@louisville.edu

Research Description:

Dr. Garbett applies biophysical approaches to the study of biomolecules and their interactions, with particular emphasis on the development of new technologies for medical diagnostics and drug development.  She is a co-inventor (with Brown Cancer Center faculty Drs. Jonathan B. Chaires and A. Bennett Jenson) of a novel, non-invasive diagnostic tool utilizing differential scanning calorimetry for early detection, diagnosis and monitoring of patients.  Her research is also focused on the characterization of plasma protein drug binding and the development of an integrated approach for preclinical testing of distribution and dosing profiles of therapeutic drugs.  The long term goals of these studies are to develop novel biomedical technologies for patient assessment and treatment that will directly impact the clinical care of patients.  Dr. Garbett’s research is funded by grants from the National Institutes of Health, the Bay Area Lyme Foundation and the University of Louisville School of Medicine.

Project 1: Characterization of Biofluid Proteomes and Interactomes for Disease Diagnostics and Patient Monitoring

DSC analysis of biofluids has been developed in our lab to provide a new and complementary approach for disease detection and monitoring that has led to four pending patent applications and could ultimately have a major impact as a novel diagnostic modality.  For some diseases, current clinical methods for disease detection are limited in accuracy, specificity, cost and/or radiation burden.  Direct analysis of small volumes of biofluids using DSC yields profiles sensitive to proteomic changes associated with disease pathology and therapeutic response. Our recent PLOS ONE publication received international press coverage for the potential role of DSC analysis in cervical cancer diagnosis.  Current focus is on the development of the technology for monitoring of recurrence and therapeutic response in melanoma patients, in collaboration with Drs. Jason A. Chesney and Donald M. Miller at the Brown Cancer Center.  We are coupling our clinical results with basic science studies of DSC profile modulations.  This has opened up new areas of investigation in disease proteomics.  This represents a paradigm shift in proteome research where the emphasis of much past and current research has been largely focused on an examination of changes in the low abundance peptide population, the peptidome, which can be correlated with disease development.  Our approaches are based on applying DSC to the analysis of different biofluid populations, the high abundance proteome and its interactions, the interactome.  We are also focused on comprehensive proteomic and lipidomic analysis to provide additional characterization of disease biology.  Our novel approach to the characterization of the patient plasma samples will provide additional understanding of the molecular processes associated with disease development and a new blood-based technology for the early assessment of disease and treatment response.

Project 2: Assessment of Blood Plasma Drug Interactions of Therapeutic Agents

Assessment of plasma protein binding is a critical part of preclinical ADMET (absorption, distribution, metabolism, excretion and toxicity) screening during drug development as these affect a drug’s activity, distribution, rate of metabolism and excretion as well as dosing regimens.  We are developing an integrated biophysical approach to characterize drug-plasma interactions.  This integrated approach is information rich, identifying the specificity and affinity of ligand interactions with plasma proteins and the thermodynamic basis of these interactions, information which is essential to fully characterize drug-plasma interactions and which cannot be determined from current approaches measuring only the fraction of unbound ligand.  It is this level of information which is required to understand the mode of binding underlying drug interactions and to provide the basis necessary for rational optimization of preclinical ADMET properties.  Moreover, the importance of characterizing in situ plasma interactions is realized from the alteration of plasma protein properties as a result of clinical status and this provides an important overlap with Project 1.  The aim to translate this work to the clinical environment for the rapid testing of drug interactions for assessment of patient therapeutic profiles as part of the design of individual patient treatment regimens.

Literature Cited:

  1. Garbett NC, Miller JJ, Jenson AB, Chaires JB. Ligand Binding Alters the Calorimetric Thermogram of Albumin. J. Clin. Ligand Assay 2006 29(4):194–197
  2. Garbett NC, Miller JJ, Jenson AB, Chaires JB. Calorimetric Analysis of the Plasma Proteome. Semin. Nephrol. 2007 27(6):621-626.PMC2692537. PMID: 18061844
  3. Garbett NC, Miller JJ, Jenson AB, Miller DM, Chaires JB. Interrogation of The Plasma Proteome with Differential Scanning Calorimetry. Clin. Chem. 2007 53(11): 2012-2014.PMID: 18030697
  4. Garbett NC, Chaires JB. Binding: A Polemic and Rough Guide. In Correia, J.J. and Detrich, III, H.W. (Eds.): Methods in Cell Biology. Amsterdam, Elsevier Inc., 2008, Vol. 84, pp. 3-23. PMID: 17964926
  5. Garbett NC, Miller JJ, Jenson AB, Chaires JB. Calorimetry outside the box: a new window into the plasma proteome. Biophys. J. 2008 94(4):1377-1383.PMC2212685. PMID: 17951300
  6. Garbett NC, Mekmaysy CS, Helm CW, Jenson AB, Chaires JB. Differential scanning calorimetry of blood plasma for clinical diagnosis and monitoring. Exp. Mol. Pathol. 2009 86:186-191.PMID: 19146849
  7. Fish DJ, Brewood GP, Kim JS, Garbett NC, Chaires JB, Benight AS. Statistical analysis of plasma thermograms measured by differential scanning calorimetry. Biophys. Chem. 2010 152(1-3):184-190.PMID: 20961680
  8. Garbett NC. The Use of Calorimetry to Study Ligand-DNA Interactions. In Aldrich-Wright, J. (Ed.): Metallointercalators: Synthesis and Techniques to Probe Their Interactions with Biomolecules. Wien, Germany, Springer-Verlag, 2011, pp. 299-324
  9. Dignam JD, Guo J, Griffith WP, Garbett, NC, Holloway A, Mueser T. Allosteric Interaction of Nucleotides and tRNAala with E. coli Alanyl-tRNA Synthetase. Biochemistry 2011 50(45):9886-9900.PMID: 21985608
  10. Wisniewski M, Garbett NC, Fish DJ, Brewood GP, Miller JJ, Chaires JB, Benight AS. Differential Scanning Calorimetry in Molecular Diagnostics. In Vitro Diagnostic Technology. 2011 17(6):29-34
  11. Garbett NC, Chaires JB. Thermodynamic Studies for Drug Design and Screening. Expert Opin. Drug Discov. 2012 7(4):299-314.PMC3496183. PMID: 22458502
  12. Rai SN, Pan J, Cambon A, Chaires JB, Garbett NC. Group Classification based on High-Dimensional Data: Application to Differential Scanning Calorimetry Plasma Thermogram Analysis of Cervical Cancer and Control Samples. Open Access Medical Statistics 2013 3:1-9
  13. Garbett NC, Merchant ML, Chaires JB, Klein JB. Calorimetric Analysis of the Plasma Proteome: Identification of Type I Diabetes Patients With Early Renal Function Decline. Biochim. Biophys. Acta 2013 1830(10):4675-4680.PMC3743444. PMID: 23665587
  14. Garbett NC, Merchant ML, Helm CW, Jenson AB, Klein JB, Chaires JB. Detection of Cervical Cancer Biomarker Patterns in Blood Plasma and Urine by Differential Scanning Calorimetry and Mass Spectrometry. PLOS ONE 2014 9(1):e84710.PMC3885574.PMID: 24416269
  15. Garbett NC, Mekmaysy CS, DeLeeuw L, Chaires JB. Clinical application of plasma thermograms.  Utility, practical approaches and considerations. Methods 2014In Press

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