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 Director, Biophysical Core Facility, James Graham Brown Cancer Center
Associate Scientist, James Graham Brown Cancer Center
Assistant Professor of Medicine (tenure-track), Department of Medicine, Division of Hematology and Oncology
Assistant Professor (Associate Appointment), Department of Biochemistry and Molecular Genetics

Contact Information:

Clinical & Translational Research Building, Room 206
James Graham Brown Cancer Center
Department of Medicine
University of Louisville
505 South Hancock Street
Louisville, KY 40202
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 biophysical and biomedical technologies for disease biomarker studies and for medical diagnostics.  She is a co-inventor (with Brown Cancer Center faculty Drs. Jonathan B. Chaires and A. Bennett Jenson) of a novel diagnostic biomarker technology based upon the biophysical technique of differential scanning calorimetry (DSC).  With collaborators at the James Graham Brown Cancer Center, we have obtained substantial preliminary data for over 10 different diseases showing that DSC profiles of blood plasma are sensitive to proteomic changes associated with multiple diseases, as well as to disease burden and therapeutic response.  The long-term goals of Dr. Garbett’s research are to develop novel biomedical technologies for patient assessment and treatment that will directly impact the clinical care of patients.  Dr. Garbett’s research has been supported by external grants from the National Institutes of Health, Department of Defense, Kentucky Science and Technology Corporation and the Bay Area Lyme Foundation.  In addition, Dr. Garbett has received internal support from the Office of the Executive Vice President for Research and Innovation, the School of Medicine and the James Graham Brown Cancer Center at the University of Louisville.

Research in the Garbett lab is focused on two main areas:

Development of Plasma Thermograms as a Novel Diagnostic Technology

We are developing DSC analysis of biofluids to provide a new and complementary approach for disease detection and monitoring.  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 work on cervical cancer received international press coverage for our findings that the DSC profile was progressively altered as the disease advanced from pre-invasive conditions to late stage cervical cancer, suggesting the potential role of DSC analysis in cervical cancer diagnosis.  We are also focused on the development of the DSC plasma thermogram technology for disease discrimination and monitoring of recurrence and therapeutic response in the melanoma, lung cancer and breast cancer settings, in collaboration with Drs. Jason Chesney, Donald Miller, Goetz Kloecker and Beth Riley at the Brown Cancer Center, and Dr. Hiram Rivas in Pulmonary Medicine.  In addition, we are developing approaches for the multi-dimensional analysis of DSC data and the application of these methods for diagnostic classification using DSC.

Application of DSC for Biomarker Discovery in Clinical Samples

We are coupling our clinical results with basic science studies of DSC profile modulations to open up new areas of investigation in disease proteomics.  DSC provides a unique physical basis with which to characterize biofluid proteomes based on its high sensitivity to unique thermal properties of biomolecules within complex mixtures as a result of disease-specific pathologies.  This represents a paradigm shift in plasma proteome research, which has been largely focused on profiling low abundance proteins and peptides associated with disease.  Our approaches are based on applying DSC to the analysis of novel biofluid populations, the high abundance proteome and the network of interacting substrates in the plasma proteome, the interactome.  We are also focused on comprehensive proteomic and lipidomic analysis to provide additional characterization of disease biology.  Our cervical cancer research has investigated the nature of DSC profile changes through mass spectrometry studies where we have obtained data supporting the interactome theory of peptide portioning to abundant plasma proteins.  We are applying our approaches in multiple disease settings to understand the biological drivers of thermogram modulation and to interrogate novel biomarker populations in clinical samples.

Representative Publications:

Application of differential scanning calorimetry for study of the blood plasma proteome

  1. Garbett, N.C., Miller, J.J., Jenson, A.B. & Chaires, J.B. (2007). Calorimetric Analysis of the Plasma Proteome. Seminars in Nephrology, 27(6), 621-626. PMCID: PMC2692537
  2. Garbett, N.C., Miller, J.J., Jenson, A.B., Miller, D.M. & Chaires, J.B. (2007). Interrogation of The Plasma Proteome with Differential Scanning Calorimetry. Clinical Chemistry, 53(11), 2012-2014. PMID: 18030697
  3. Garbett, N.C., Miller, J.J., Jenson, A.B. & Chaires, J.B. (2008). Calorimetry outside the box: a new window into the plasma proteome. Biophysical Journal, 94(4), 1377-1383. PMCID: PMC2212685
  4. Garbett, N.C., and Brock, G.N. “Methods of Characterizing and/or Predicting Risk Associated with a Biological Sample Using Thermal Stability Profiles,” U.S. PCT Application PCT/US16/57416, Oct. 2016.

Development of DSC for clinical diagnostics

  1. Garbett, N.C., Mekmaysy, C.S., Helm, C.W., Jenson, A.B. & Chaires, J.B. (2009). Differential scanning calorimetry of blood plasma for clinical diagnosis and monitoring. Experimental and Molecular Pathology, 86, 186-191. PMID: 19146849
  2. Garbett, N.C., Merchant, M.L., Helm, C.W., Jenson, A.B., Klein, J.B. & Chaires, J.B. (2014). Detection of Cervical Cancer Biomarker Patterns in Blood Plasma and Urine by Differential Scanning Calorimetry and Mass Spectrometry. PLOS ONE, 9(1), e84710. PMCID: PMC3885574
  3. Garbett, N.C., Brock, G.N., Chaires, J.B., Mekmaysy, C.S., Sivils, K.L., Harley, J.B., Rovin, B.H., Kulasekera, K.B. & Jarjour, W.N. (2017). Characterization and Classification of Lupus Patients Based on Plasma Thermograms. PLOS ONE, 12(11), e0186398.  PMCID: PMC5693473
  4. Velazquez-Campoy, A., Vega, S., Sanchez-Gracia, O., Lanas, A., Rodrigo, A., Kaliappan, A., Hall, M.B., Nguyen, T.Q., Brock, G.N., Chesney, J.A., Garbett, N.C.& Abian, O. (2018). Thermal Liquid Biopsy for Monitoring Melanoma Patients Under Surveillance During Treatment: A Pilot Study. Biochimica et Biophysical Acta - General Subjects, 1862(8), 1701-1710. PMID: 29705200

Development of statistical approaches for the multi-dimensional analysis of DSC data

  1. Fish, D.J., Brewood, G.P., Kim, J.S., Garbett, N.C., Chaires, J.B. & Benight, A.S. (2010). Statistical analysis of plasma thermograms measured by differential scanning calorimetry. Biophysical Chemistry, 152(1-3), 184-190. PMID: 20961680
  2. Rai, S.N., Pan, J., Cambon, A., Chaires, J.B. & Garbett, N.C. (2013). 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, 3, 1-9.
  3. Garbett, N.C. & Brock, G.N. (2016). Differential scanning calorimetry as a complementary diagnostic tool for the evaluation of biological samples. Biochimica et Biophysica Acta, 1860(5), 981-989.  PMID: 26459005
  4. Kendrick, S.K., Zheng, Q., Garbett, N.C. & Brock G.N. (2017). Application and interpretation of functional data analysis techniques to differential scanning calorimetry data from lupus patients. PLOS ONE, 12(11), e0186232.  PMCID: PMC5679774

Use of biophysical approaches for the characterization of biomolecules and their interactions

  1. Wheelhouse, R.T., Garbett, N.C., Buurma, N.J. & Chaires, J.B. (2010). Probing the Molecular Recognition of a DNA-RNA Hybrid Duplex. Angewandte Chemie (International Edition in English), 49(18), 3207-3210. PMCID: PMC3517034
  2. Petraccone, L., Garbett, N.C., Chaires, J.B. & Trent, J.O. (2010). An Integrated Molecular Dynamics (MD) and Experimental Study of Higher Order Human Telomeric Quadruplexes. Biopolymers, 93(6), 533-548. PMCID: PMC3131549
  3. Dignam, J.D., Guo, J., Griffith, W.P., Garbett, N.C., Holloway, A. & Mueser, T. (2011). Allosteric Interaction of Nucleotides and tRNAala with E. coli Alanyl-tRNA Synthetase. Biochemistry, 50(45), 9886-9900. PMID: 21985608
  4. Khanal, A., Ullum, C., Kimbrough, C.W., Garbett, N.C., Burlison, J.A., McNally, M.W., Chuong, P., El-Baz, A.S., Jasinski, J.B. & McNally, L.R. (2015). Multispectral optoacoustic tomography-based detection of pancreatic tumors in vivo by using tumor targeted mesoporous silica-coated gold nanorods. Nano Research, DOI 10.1007/s12274-015-0886-8.

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