Thomas C. Rich, Ph.D.
Biography
Dr. Thomas C. Rich, Professor, received his Baccalaureate with Honors in Engineering and Masters in Aerospace Engineering from Georgia Institute of Technology in Atlanta, GA, and his Ph.D. in Biomedical Engineering from Vanderbilt University in Nashville, TN. Dr. Rich is the Director of the Bioimaging Core Facility in the Frederick P. Whiddon College of Medicine.
Research
Our group has a long-standing goal to understand the mechanisms of signaling specificity and how a small set of intracellular signals orchestrate wide varieties of cellular functions. To accomplish this goal, we need to measure both signals produced in response to a specific stimulus and the response to this stimulus within single cells. Toward this end, I spent the early part of my career developing a series of single cell cAMP sensors. We have used these sensors to discern the roles of specific phosphodiesterases (PDEs) in regulating cAMP signals near the plasma membrane and in contributing to cAMP gradients. We developed unique approaches for discerning roles of GRK and PKA in regulating 尾2 adrenergic receptors and the role(s) of PKA-mediated regulation of PDE4 in shaping cAMP signals. We have used these approaches to estimate the magnitude of PDE activity in discrete subcellular compartments.
The critical need for assessment of localized cAMP, NO, cGMP, and Ca2+ signals led to an ongoing collaboration with Dr. Silas Leavesley in which we are validating hyperspectral imaging (HSI) approaches for accurate FRET/fluorescence measurement in cells and tissues. This requires development, implementation, and testing of novel filtering approaches/light sources to allow real-time imaging. Recently we have focused on excitation scan-based HSI approaches that provide 100-fold increases in signal-to-noise ratio over traditional FRET measurements, and allow quantitative assessment of FRET/fluorescence signals at discrete regions within cells. These approaches also allow simultaneous real-time assessment of multicolor immunofluorescence and dynamics of cAMP and Ca2+ signals. We are implementing HSI approaches for measurement of fluorescence/FRET signals in cultured cells and intact tissue preparations. We have used these approaches to detect oscillatory cAMP signals in localized regions of pulmonary microvascular endothelial cells and discrete cAMP signals from microdomains at the basal face (bottom) of human airway smooth muscle cells. These image data demonstrate the ability of HSI approaches to visualize previously unresolvable cAMP signals 鈥� allowing us a unique view into the complexities of signaling pathways. We are now validating approaches to assess image parameters utilizing dynamic region of interest tracking approaches developed by our collaborator, Dr. Michael Francis. This collaborative group is uniquely suited to optimize approaches for the simultaneous measurement of cAMP, NO, cGMP, and Ca2+ signals within the 鈥榯urbulent maelstrom of the cellular environment鈥�.
Publications
S.C. Johnson, N.S. Annamdevula, S.J. Leavesley, C.M. Francis, T.C. Rich, Hyperspectral imaging and dynamic region of interest tracking approaches to quantify localized cAMP signals, Biochem. Soc. Trans. accepted (2024).
M. Parker, N.S. Annamdevula, D.J. Pleshinger, Z. Ijaz, J. Jalkh, R. Penn, D. Deshpande, T.C. Rich, S.J. Leavesley, Comparing performance of spectral image analysis approaches for detection of cellular signals in time-lapse hyperspectral imaging fluorescence excitation-scanning microscopy, Bioengineering 10 (2023) 10.3390/bioengineering10060642.
J.M. Knighten, T. Aziz, D.J. Pleshinger, N. Annamdevula, T.C. Rich, M.S. Taylor, J.F. Andrews, C.T. Macarilla, C.M. Francis, Algorithm for biological second messenger analysis with dynamic regions of interest, PLoS One 18 (2023) e0284394.
A. Nguyen, K. Battle, S.S. Paudel, N. Xu, J. Bell, L. Ayers, C. Chapman, A. Singh, S. Palanki, T.C. Rich, D. Alvarez, T. Stevens, D. Tambe, Integrative Toolkit to Analyze Cellular Signals: Forces, Motion, Morphology, and Fluorescence, JoVE 5 (2022) 10.3791/63095.
E. Arbov, A. Tayara, S. Wu, T.C. Rich, B.M. Wagener, COVID-19 and long-term outcomes: Lessons from other critical care illnesses and potential mechanism, Am. J. Respir. Cell. Mol. Biol. 67 (2022) 275-283.
C.M. Browning, R. Cloutier, T.C. Rich, S.J. Leavesley, Endoscopy lifetime systems architecture: Scoping out the past to diagnose the future technology, Systems 10 (2022 ) 189. doi: 110.3390/systems10050189.
T.C. Rich, S.J. Leavesley, A.P. Brandon, C.A. Evans, S.V. Raju, B.M. Wagener, Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the 尾2 -adrenergic receptor, FASEB J. 35 (2021) 35:e21946. doi: 21910.21096/fj.202002712RR.
C.M. Browning, J. Deal, S. Mayes, A. Arshad, T.C. Rich, S.J. Leavesley, Excitation-scanning hyperspectral video endoscopy: enhancing the light at the end of the tunnel, Biomedical Optics Express 12 (2020) 247-271.
P.F. Favreau, J.A. Deal, B. Harris, D.S. Weber, T.C. Rich, S.J. Leavesley, J. Biophotonics., Label-free spectroscopic tissue characterization using fluorescence excitation-scanning spectral imaging, J. Biophotonics 13 (2020) e201900183.
J. Deal, D.J. Pleshinger, S.C. Johnson, S.J. Leavesley, T.C. Rich, Milestones in the development and implementation of FRET-based sensors of intracellular signals: A biological perspective of the history of FRET, Cellular Signalling 75 (2020) doi.org/10.1016/j.cellsig.2020.109769.
S.J. Leavesley, B. Sweat, C. Abbott, P. Favreau, T.C. Rich, A theoretical-experimental methodology for assessing the sensitivity of biomedical spectral imaging platforms, assays, and analysis methods, J. Biophotonics 11 (2018) doi: 10.1002/jbio.201600227.
N.S. Annamdevula, R. Sweat, J.R. Griswold, K. Trinh, C. Hoffman, S. West, J. Deal, A.L. Britain, K. Jalink, T.C. Rich, S.J. Leavesley, Spectral imaging of FRET-based sensors reveals sustained cAMP gradients in three spatial dimensions, Cytometry A 93 (2018) 1029-1038.
S.J. Leavesley, T.C. Rich, Overcoming limitations of FRET measurements, Cytometry A. 89 (2016) 325-327.
W. Xin, W.P. Feinstein, A.L. Britain, C. Ochoa, B. Zhu, W. Richter, S.J. Leavesley, T.C. Rich, Estimating the magnitude of near-membrane PDE4 activity in living cells, Am. J. Physiol. Cell Physiol. 309 (2015) C415-C424.