Dr. Michael G. Nichols Profile

Dr. Michael G. Nichols

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Dr. Michael G. Nichols is Professor and Director of the Graduate Programs in Physics and Medical Physics at Creighton University. He received his B.S. in Physics from Harvey Mudd College in 1990, and a Ph.D. in Physics from the University of Rochester in 1996. His research interests include biophysical optics, metabolic imaging, fluorescence microscopy, single molecule techniques, and cellular biomechanics. He is the Director of the Integrated Biomedical Imaging Facility (IBIF) of Creighton University.

SPIE Journal Paper | 9 October 2021 Open Access

Development and characterization of phasor-based analysis for FLIM to evaluate the metabolic and epigenetic impact of HER2 inhibition on squamous cell carcinoma cultures

Dan Pham, Christina Miller, Molly Myers, Dominick Myers, Laura Hansen, Michael Nichols

JBO, Vol. 26, Issue 10, 106501, (October 2021) https://doi.org/10.1117/12.10.1117/1.JBO.26.10.106501

KEYWORDS: Luminescence, Fluorescence lifetime imaging, Mode conditioning cables, Vehicle control, Cancer, Tumors, Tumor growth modeling, Statistical analysis, Skin cancer, Tissue optics

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Significance: Deranged metabolism and dysregulated growth factor signaling are closely associated with abnormal levels of proliferation, a recognized hallmark in tumorigenesis. Fluorescence lifetime imaging microscopy (FLIM) of endogenous nicotinamide adenine dinucleotide (NADH), a key metabolic coenzyme, offers a non-invasive, diagnostic indicator of disease progression, and treatment response. The model-independent phasor analysis approach leverages FLIM to rapidly evaluate cancer metabolism in response to targeted therapy. Aim: We combined lifetime and phasor FLIM analysis to evaluate the influence of human epidermal growth factor receptor 2 (HER2) inhibition, a prevalent cancer biomarker, on both nuclear and cytoplasmic NAD(P)H of two squamous cell carcinoma (SCC) cultures. While better established, the standard lifetime analysis approach is relatively slow and potentially subject to intrinsic fitting errors and model assumptions. Phasor FLIM analysis offers a rapid, model-independent alternative, but the sensitivity of the bound NAD(P)H fraction to growth factor signaling must also be firmly established. Approach: Two SCC cultures with low- and high-HER2 expression, were imaged using multiphoton-excited NAD(P)H FLIM, with and without treatment of the HER2 inhibitor AG825. Cells were challenged with mitochondrial inhibition and uncoupling to investigate AG825’s impact on the overall metabolic capacity. Phasor FLIM and lifetime fitting analyses were compared within nuclear and cytoplasmic compartments to investigate epigenetic and metabolic impacts of HER2 inhibition. Results: NAD(P)H fluorescence lifetime and bound fraction consistently decreased following HER2 inhibition in both cell lines. High-HER2 SCC74B cells displayed a more significant response than low-HER2 SCC74A in both techniques. HER2 inhibition induced greater changes in nuclear than cytoplasmic compartments, leading to an increase in NAD(P)H intensity and concentration. Conclusions: The use of both, complementary FLIM analysis techniques together with quantitative fluorescence intensity revealed consistent, quantitative changes in NAD(P)H metabolism associated with inhibition of growth factor signaling in SCC cell lines. HER2 inhibition promoted increased reliance on oxidative phosphorylation in both cell lines.

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SPIE Journal Paper | 8 November 2018 Open Access

Aminoglycosides rapidly inhibit NAD(P)H metabolism increasing reactive oxygen species and cochlear cell demise

Danielle Desa, Michael Nichols, Heather Jensen Smith

JBO, Vol. 24, Issue 05, 051403, (November 2018) https://doi.org/10.1117/12.10.1117/1.JBO.24.5.051403

KEYWORDS: Sensors, Luminescence, Mode conditioning cables, Silver, Oxygen, Cell death, Electron transport, Acquisition tracking and pointing, Resolution enhancement technologies, Proteins

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SPIE Journal Paper | 17 February 2015 Open Access

Gentamicin differentially alters cellular metabolism of cochlear hair cells as revealed by NAD(P)H fluorescence lifetime imaging

Lyandysha Zholudeva, Kristina Ward, Michael Nichols, Heather Jensen Smith

JBO, Vol. 20, Issue 05, 051032, (February 2015) https://doi.org/10.1117/12.10.1117/1.JBO.20.5.051032

KEYWORDS: Sensors, Luminescence, Mode conditioning cables, Silver, Fluorescence lifetime imaging, Proteins, Electron transport, Molecules, Quantum efficiency, Oxidation

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SPIE Journal Paper | 1 March 2007 Open Access

Determination of hair cell metabolic state in isolated cochlear preparations by two-photon microscopy

LeAnn Tiede, Sonia Rocha-Sanchez, Richard Hallworth, Michael Nichols, Kirk Beisel

JBO, Vol. 12, Issue 02, 021004, (March 2007) https://doi.org/10.1117/12.10.1117/1.2714777

KEYWORDS: Luminescence, Tissues, Mode conditioning cables, Two photon excitation microscopy, Flavoproteins, Cyanide, Acquisition tracking and pointing, Two photon imaging, Neurons, Oxidation

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