Person:
Platt, Manu O.

Associated Organization(s)
Organizational Unit
Wallace H. Coulter Department of Biomedical Engineering
The joint Georgia Tech and Emory department was established in 1997
ORCID
ArchiveSpace Name Record

Publication Search Results

Now showing 1 - 4 of 4
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    Race, Reparations and Reconciliation After the Genome
    (Georgia Institute of Technology, 2017-04-04) Benjamin, Ruha ; Nelson, Alondra ; Platt, Manu O. ; Pollock, Anne
    All are welcome for a public dialogue featuring two world-leading experts on the intersections of race and biomedicine in science and in society. Alondra Nelson, Columbia University, author of Body and Soul: The Black Panther Party and the Fight Against Medical Discrimination and The Social Life of DNA: Race, Reparations, and Reconciliation after the Genome. Ruha Benjamin, Princeton University, author of People’s Science: Bodies and Rights on the Stem Cell Frontier. Co-sponsored by The Black Feminist Think Tank and the Working Group on Race and Racism in Contemporary Biomedicine, with the generous support of GT-FIRE
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    “What’s Eating You?” Quantifying Proteolytic Activity in Health and Disease with Novel Assays and Computational Models
    (Georgia Institute of Technology, 2011-09-13) Platt, Manu O.
    Cathepsins are enzymes with the most powerful human collagenase and elastase activity that are upregulated at sites of normal tissue remodeling and during tissue-destructive disease progression. We study them in the context of tissue remodeling in cancer progression and cardiovascular diseases such as sickle cell disease and atherosclerosis. They are synthesized as stable inactive precursors requiring activation by propeptide cleavage, and detection of mature cathepsins and quantification of specific activity have proven difficult due to instability of the mature, active enzyme extracellularly, diminishing appreciation for their involvement in a large number of diseases. During this seminar, we will discuss our studies of this family of powerful proteases in diseases with particular attention to cancer and sickle cell disease. First, we will discuss the important development of a reliable, sensitive method of zymography to detect the activity of mature cathepsins K, L, S, and V and integrating that assay with the development of a computational kinetic model to predict cathepsin-mediated tissue remodeling by cells during advancing disease. Secondly, we will discuss our applications of these technologies and potential use as both diagnostic and prognostic indicators of human breast, lung, and cervical cancer as well as newly identified mechanisms of cathepsin activity in complications of stroke in children with sickle cell disease.
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    Platt Lab Overview
    (Georgia Institute of Technology, 2009-06-17) Platt, Manu O.
  • Item
    Role of Shear Stress in the Differential Regulation of Endothelial Cathepsins and Cystatin C
    (Georgia Institute of Technology, 2006-07-06) Platt, Manu O.
    The importance of shear stress in vascular biology and pathophysiology has been highlighted by the focal development patterns of atherosclerosis, abdominal aortic aneurysms, and heart valve disease in regions exposed to disturbed flow leading to low or oscillatory shear stress at the wall of the blood vessel or the surface of the valve leaflet. The novel and significant finding of this study is that mouse aortic endothelial cell exposure to pro-atherogenic oscillatory shear stress (OS) (+/- 5 dynes/cm2) increased their production of cathepsins, the family of lysosomal cysteine proteases that are potent elastases and collagenases leading to protease degradation and remodeling of the extracellular matrix structural components. Conversely, atheroprotective unidirectional laminar shear stress (LS) (15 dynes/cm2) decreased elastase and gelatinase activities of endothelial cells through a shear stress mediated reduction in cathepsins K, L, and S activity. Their endogenous inhibitor, cystatin C, was found to be inversely regulated by shear stress; LS increased its secretion by endothelial cells while OS decreased it. Binding of free cystatin C in the conditioned media to carboxymethylated papain coated agarose beads led to an increase in cathepsin activity since the available cathepsin was not inhibited. To verify these findings in human samples, immunohistochemical analysis of cystatin C and cathepsin K was performed on human coronary arteries. Cathepsin K stained strongly in the endothelial layer of vessels with degraded internal elastic lamina while cystatin C staining intensity was strongest overlying minimally diseased vessels. Additional roles for cathepsins K, L, and S were found in endothelial cell alignment in response to unidirectional laminar shear stress, endothelial cell migration, and programmed cell death. We conclude that there is an inverse regulation of cathepsins and cystatin C in endothelial cells by LS and OS and identify the cathepsin family of proteases as potential targets for therapeutic intervention of cardiovascular disease development at sites of disturbed flow.