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

Current Positions:

Associate Professor of Medicine (tenured), Department of Medicine, Division of Medical Oncology and Hematology
Associate Appointment, Department of Biochemistry and Molecular Genetics
Director, Biophysical Facility, UofL Health – Brown Cancer Center
Member, Experimental Therapeutics & Diagnostics Program, Brown Cancer Center

Contact Information:

Clinical & Translational Research Building, Room 206
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 UofL Health – 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 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 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 UofL Health – 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.  Lastly, we are working with collaborators in the Department of Bioengineering to develop a point-of-care DSC device for patient testing in the clinical environment.

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 also are 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:

Novel application of differential scanning calorimetry for study of the blood plasma proteome

  1. Garbett NC, Miller JJ, Jenson AB, Miller DM, Chaires JB.  Interrogation of the plasma proteome with differential scanning calorimetry.  Clinical Chemistry 2007 Nov;53(11):2012-2014.  doi: 10.1373/clinchem.2007.091165.  PMID: 18030697.
  1. Garbett NC, Miller JJ, Jenson AB, Chaires JB.  Calorimetry outside the box: a new window into the plasma proteome.  Biophysical Journal 2008 Feb 15;94(4):1377-1383.  doi: 10.1529/biophysj.107/119453.  Epub 2007 Oct 19.  PMID: 17951300.  PMCID: PMC2212685.
  2. Garbett NC, Mekmaysy CS, Helm CW, Jenson AB, Chaires JB.  Differential scanning calorimetry of blood plasma for clinical diagnosis and monitoring.  Experimental & Molecular Pathology 2009 Jun;86(3):186-191.  doi: 10.1016/j.yexmp.2008.12.001.  PMID: 19146849. 

Development of DSC for clinical diagnostics

  1. 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 Jan 8;9(1):e84710.  doi: 10.1371/journal.pone.0084710.  PMID: 24416269.  PMCID: PMC3885574.
  1. Garbett NC, Brock GN, Chaires JB, Mekmaysy CS, Sivils KL, Harley JB, Rovin BH, Kulasekera KB, Jarjour WN.  Characterization and classification of lupus patients based on plasma thermograms.  PLoS One 2017 Nov 17;12(11):e0186398.  doi: 10.1371/journal.pone.0186398.  PMID: 29149219.  PMCID: PMC5693473.
  2. Velazquez-Campoy A, Vega S, Sanchez-Gracia O, Lanas A, Rodrigo A, Kaliappan A, Hall MB, Nguyen TQ, Brock GN, Chesney JA, Garbett NC, Abian O.  Thermal liquid biopsy for monitoring melanoma patients under surveillance during treatment: A pilot study.  Biochimica et Biophysica Acta - General Subjects 2018 Aug;1862(8):1701-1710.  doi: 10.1016/j.bbagen.2018.04.020.  PMID: 29705200.  PMCID: PMC6483604.
  3. Schneider G, Kaliappan A, Nguyen TQ, Buscaglia R, Brock GN, Hall MB, DeSpirito C, Wilkey DW, Merchant ML, Klein JB, Wiese TA, Rivas-Perez HL, Kloecker GH, Garbett NC.  The utility of differential scanning calorimetry curves of blood plasma for diagnosis, subtype differentiation and predicted survival in lung cancer.  Cancers 2021 Oct 23;13(21):5326.  doi: 10.3390/cancers13215326.  PMID: 34771491.  PMCID: PMC8582427.

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

  1. Fish DJ, Brewood GP, Kim JS, Garbett NC, Chaires JB, Benight AS.  Statistical analysis of plasma thermograms measured by differential scanning calorimetry.  Biophysical Chemistry 2010 Nov;152(1-3):184-190.  doi: 10.1016/j.bpc.2010.09.007.  PMID: 20961680. 
  1. Garbett NC, Brock GN.  Differential scanning calorimetry as a complementary diagnostic tool for the evaluation of biological samples.  Biochimica et Biophysica Acta 2016 May;1860(5):981-989.  doi: 10.1016/j.bbagen.2015.10.004.  PMID: 26459005.  PMCID: PMC4799750.
  2. Rai SN, Srivastava S, Pan J, Wu X, Rai SP, Mekmaysy CS, DeLeeuw L, Chaires JB, Garbett NC.  Multi-group diagnostic classification of high-dimensional data using differential scanning calorimetry plasma thermograms.  PLoS One 2019 Aug 20;14(8):e0220765.  doi: 10.1371/journal.pone.0220765.  PMID: 31430304.  PMCID: PMC6701772.

PubMed Information