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Blake Monroe

Mentor: Ethan J. Anderson, PhD

Year Entered Into Program: 2017

Terminal Degree(s) Received: PhD 2021

Graduate Program: PSET

Research Description

The Role of Biogenic Aldehydes in the Development of Cardiac Fibrosis

Fibrosis is a well-known risk factor for numerous cardiac pathologies, particularly arrhythmia and heart failure, and is worth studying because of its association with cardiovascular complications of diabetes and obesity, both widespread conditions. One of the working hypotheses of the lab is that biogenic aldehydes, generated enzymatically and non-enzymatically as a byproduct of oxidative stress, could be a contributing factor underlying cardiac fibrosis.  The goal of my research is to establish these reactive aldehydes' roles in the pathology of cardiac fibrosis and the pathways by which they act in order to explore the therapeutic value of scavenging them.  Thus far, we have determined that the reactive catecholaldehyde, 3,4-Dihydroxyphenylacetaldehyde (DOPAL), is a potent inducer of collagen secretion in human atrial cardiac myofibroblasts.  We have also determined DOPAL is an agonist for the receptor for advanced glycation endproducts (RAGE), which could explain the collagen deposition.

Awards

  • Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2017-2019
  • East Carolina University, Brody School of Medicine Research Assistantship, 2015 - 2016

Publications

  1. Nelson, MA,M., Efird, J., Kew, K.A., Katunga, L.A., Monroe, T.B., Doorn, J.A., Beatty, C.N., Shi, Q., Akhter, S.A., Alwair, H., Robidoux, J., Anderson, E.J.†: Enhanced catecholamine flux and impaired carbonyl metabolism disrupt cardiac mitochondrial OxPHOS in diabetes patients. Antioxid Redox Signal 2020 Oct 16 2020 https://doi-org.proxy.lib.uiowa.edu/10.1089/ars.2020.8122  PMID: 33066717
  2. Bell, K, Lansakarab, T, Crawford, R, Monroe, TB, Tivanskib, AV, Salem, AK, and Lewis L. Stevens.: Mechanical cues protect against silica nanoparticle exposure in SH-SY5Y neuroblastoma. Toxicology in Vitro, 2020 Oct 16;105031. https://doi.org/10.1016/j.tiv.2020.105031  PMID: 33075489
  3. Monroe, T.B. and Anderson, E.: A Highly Sensitive, Reproducible Assay for Determining 4-hydroxynonenal Protein Adducts in Biological Material. Bioprotocols, 2019 Oct 5. doi: 10.21769/BioProtoc.3383.
  4. Nelson, M.M., Builta, Z.J., Monroe, T.B., Doorn, J.A., and Anderson, E.J.:  Biochemical Characterization of the Catecholaldehyde Reactivity of L-carnosine and Its Therapeutic Potential in Human Myocardium. Amino Acids, 51(1):97,102, 2019.  PMCID: PMC6924506
  5. Anderson, E.J., Vistoli, G., Katunga, L.A., Funai, K., Regazzoni, L., Monroe, T.B., Gilardoni, E., Cannizzaro, L., Colzani, M., De Maddis, D., Rossoni, G., Canevotti, R., Gagliardi, S., Carini, M., and Aldini, G.:  A Carnosine Analog Mitigates Metabolic Disorders of Obesity by Reducing Carbonyl Stress. J Clin Invest, 128(12):5280-5293, 2018.  PMCID: PMC6264636
     

Research