Karen Weikel, PhD
Boston University College of General Studies

PhD, Tufts University
MS, Tufts University

My interest in metabolic diseases, especially those associated with human nutrition, began as a graduate student at the Friedman School of Nutrition Science and Policy at Tufts University. During my Masters and Doctoral degree programs I worked at the Jean Mayer Human Nutrition Research Center on Aging in the Laboratory for Nutrition and Vision Research. I was involved in several projects which studied the effects of various nutrients on the development of age-related vision disorders such as cataract and age-related macular degeneration (AMD). My doctoral thesis focused on the influence of dietary glycemic index on the development of early AMD. The glycemic index is a relative measure of blood glucose levels following consumption of carbohydrate. A food with a high glycemic index will induce a greater rise in blood glucose levels following its consumption than a food with a low glycemic index. Epidemiologic evidence indicates that people who consume low glycemic index diets are at a reduced risk for AMD, but the mechanism governing this association was not known. I created a new mouse model for early AMD in which we found that feeding mice a high glycemic index diet, compared to a low glycemic index diet, accelerated the aging process in the retina, the site of damage during AMD. Oxidative stress, as indicated by the accumulation of advanced glycation end products, as well as impairment of intracellular proteolysis machinery (the ubiquitin proteasome pathway, specifically) appeared to be involved in the mechanism governing the effects of the high glycemic index diet on retinal aging. Moreover, studies in human cell lines revealed cross-talk between the ubiquitin proteasome pathway, which degrades short-lived proteins, and another cellular quality control process which degrades long-lived proteins, called autophagy.

I continued to study autophagy when I began my postdoctoral fellowship in the Diabetes and Metabolism Research Unit at Boston University-Boston Medical Center, but my research focus shifted from vision-related debilities to diabetic complications of the macrovasculature. Patients with type 2 diabetes are more likely to develop atherosclerosis and other cardiovascular complications. However, it is not clear how the diabetic environment damages the aorta, one of the most common sites for the development of atherosclerosis. I initiated studies in endothelial cells that line the human aorta in which we found that high levels of glucose and fatty acids impaired autophagy and increased endothelial cell inflammation and vulnerability to death. We also revealed a novel interaction between autophagy and AMP-activated protein kinase (AMPK), an enzyme that regulates key events in energy metabolism and cellular stress responses. Decreased AMPK activity has been identified as a contributing factor to atherosclerotic cardiovascular disease, but the mechanisms causing this downregulation, as well as the factors that could help restore AMPK signaling in the nutrient-laden vasculature characteristic of poorly-controlled diabetics, is not well understood. By enhancing our understanding of how excess glucose and fatty acids alter AMPK and other cellular processes such as autophagy and inflammation, this work may provide insight into the development of more effective therapies for diabetic vascular dysfunction.
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Lan F, Weikel KA, Cacicedo JM, Ido Y. Resveratrol-Induced AMP-Activated Protein Kinase Activation Is Cell-Type Dependent: Lessons from Basic Research for Clinical Application. Nutrients. 2017 Jul 14; 9(7).View Related Profiles. PMID: 28708087.
  2. Weikel KA, Cacicedo JM, Ruderman NB, Ido Y. Knockdown of GSK3ß increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells. Biosci Rep. 2016 Oct; 36(5).View Related Profiles. PMID: 27534430; PMCID: PMC5025810; DOI: 10.1042/BSR20160174;.
  3. Weikel KA, Ruderman NB, Cacicedo JM. Unraveling the actions of AMP-activated protein kinase in metabolic diseases: Systemic to molecular insights. Metabolism. 2016 May; 65(5):634-45.View Related Profiles. PMID: 27085772; PMCID: PMC4834453; DOI: 10.1016/j.metabol.2016.01.005;.
  4. Ido Y, Duranton A, Lan F, Weikel KA, Breton L, Ruderman NB. Resveratrol prevents oxidative stress-induced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes. PLoS One. 2015; 10(2):e0115341.View Related Profiles. PMID: 25647160; PMCID: PMC4315597; DOI: 10.1371/journal.pone.0115341;.
  5. Weikel KA, Cacicedo JM, Ruderman NB, Ido Y. Glucose and palmitate uncouple AMPK from autophagy in human aortic endothelial cells. Am J Physiol Cell Physiol. 2015 Feb 1; 308(3):C249-63.View Related Profiles. PMID: 25354528; PMCID: PMC4312840; DOI: 10.1152/ajpcell.00265.2014;.
  6. Rowan S, Weikel K, Chang ML, Nagel BA, Thinschmidt JS, Carey A, Grant MB, Fliesler SJ, Smith D, Taylor A. Cfh genotype interacts with dietary glycemic index to modulate age-related macular degeneration-like features in mice. Invest Ophthalmol Vis Sci. 2014 Jan 23; 55(1):492-501. PMID: 24370827; PMCID: PMC3901416; DOI: 10.1167/iovs.13-12413;.
  7. Weikel KA, Garber C, Baburins A, Taylor A. Nutritional modulation of cataract. Nutr Rev. 2014 Jan; 72(1):30-47. PMID: 24279748; PMCID: PMC4097885; DOI: 10.1111/nure.12077;.
  8. Birarda G, Holman EA, Fu S, Weikel K, Hu P, Blankenberg FG, Holman HY, Taylor A. Synchrotron infrared imaging of advanced glycation endproducts (AGEs) in cardiac tissue from mice fed high glycemic diets. Biomed Spectrosc Imaging. 2013; 2(4):301-315. PMID: 26500847.
  9. Weikel KA, Chiu CJ, Taylor A. Nutritional modulation of age-related macular degeneration. Mol Aspects Med. 2012 Aug; 33(4):318-75. PMID: 22503690; PMCID: PMC3392439; DOI: 10.1016/j.mam.2012.03.005;.
  10. Weikel KA, Fitzgerald P, Shang F, Caceres MA, Bian Q, Handa JT, Stitt AW, Taylor A. Natural history of age-related retinal lesions that precede AMD in mice fed high or low glycemic index diets. Invest Ophthalmol Vis Sci. 2012 Feb 02; 53(2):622-32. PMID: 22205601; PMCID: PMC3317410; DOI: 10.1167/iovs.11-8545;.
Showing 10 of 12 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 12 publications over 8 distinct years, with a maximum of 2 publications in 2012 and 2013 and 2014 and 2016

In addition to these self-described keywords below, a list of MeSH based concepts is available here.

cell biology
human metabolism
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