{"id":245,"date":"2008-09-15T12:10:49","date_gmt":"2008-09-15T16:10:49","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/busm-pathology\/?page_id=245"},"modified":"2016-09-26T08:07:26","modified_gmt":"2016-09-26T12:07:26","slug":"t-m-ruenger-md-phd","status":"publish","type":"page","link":"https:\/\/www.bumc.bu.edu\/busm-pathology\/home\/people_main\/t-m-ruenger-md-phd\/","title":{"rendered":"T. M. Ruenger, MD PhD"},"content":{"rendered":"<p><a href=\"https:\/\/www.bumc.bu.edu\/busm-pathology\/files\/2008\/09\/tr.jpg\"><img loading=\"lazy\" class=\"alignleft size-medium wp-image-246\" style=\"margin: 0px 20px;\" src=\"https:\/\/www.bumc.bu.edu\/busm-pathology\/files\/2008\/09\/tr.jpg\" alt=\"\" width=\"160\" height=\"238\" \/><\/a><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 3pt; text-align: left; padding-left: 60px;\"><strong><span style=\"font-family: Tahoma;\">Thomas M. Ruenger <\/span><span style=\"font-size: 10pt; font-family: Tahoma;\">(R\u00fcnger)<\/span><span style=\"font-family: Tahoma;\">, MD PhD <\/span><span style=\"font-family: Tahoma;\">(equiv.)<\/span><\/strong><span style=\"font-family: Tahoma;\"><br \/>\nProfessor and Vice-Chair of Dermatology<br \/>\n<\/span><span style=\"font-family: Tahoma;\">Professor of Pathology and Laboratory Medicine<br \/>\nDepartment of Dermatology, Boston University School of Medicine<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 3pt; text-align: left;\"><span style=\"color: #ffffff;\">&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 3pt; text-align: left;\">\n<p class=\"MsoNormal\" style=\"margin-top: 3pt; text-align: left;\"><strong><span style=\"font-family: Tahoma;\">Contact Info<\/span><\/strong><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 3pt; text-align: left; padding-left: 30px;\"><span style=\"font-family: Tahoma;\"> e-mail: truenger@bu.edu<\/span><\/p>\n<h3><\/h3>\n<h3><\/h3>\n<h3><strong><span style=\"font-family: Tahoma;\">Education and Training:<\/span><\/strong><\/h3>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"font-family: Tahoma;\">Medical Schools, University of Ulm and University of Kiel, Germany<br \/>\nPostdoctoral Fellowship, Laboratory of Molecular Carcinogenesis, <\/span><span style=\"font-family: Tahoma;\">NCI<\/span><span style=\"font-family: Tahoma;\">, NIH<br \/>\nDermatology and Allergology Residency, University of W\u00fcrzburg, Germany<\/span><\/p>\n<h3><strong><span style=\"font-family: Tahoma;\">Clinical Interests:<\/span><\/strong><\/h3>\n<ul>\n<li><span style=\"font-family: Tahoma;\">Photodermatology:<\/span>\n<ul>\n<li><span style=\"font-family: Tahoma;\">phototherapy<\/span><\/li>\n<li><span style=\"font-family: Tahoma;\">photosensitive skin diseases<\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<ul>\n<li><span style=\"font-family: Tahoma;\">Dermato-oncology<\/span><\/li>\n<\/ul>\n<h3><strong><span style=\"font-family: Tahoma;\">Research Interests:<\/span><\/strong><\/h3>\n<ul>\n<li><span style=\"font-family: Tahoma;\">Photobiology: <\/span>\n<ul>\n<li><span style=\"font-family: Tahoma;\">Repair of UV-induced <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage<\/span><\/li>\n<li><span style=\"font-family: Tahoma;\">UV-mutagenesis<\/span><\/li>\n<li><span style=\"font-family: Tahoma;\">UV-induced <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage signaling <\/span><\/li>\n<li><span style=\"font-family: Tahoma;\">UV-induced <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage responses<\/span><\/li>\n<li><span style=\"font-family: Tahoma;\">Photocarcinogenesis<\/span><\/li>\n<li><span style=\"font-family: Tahoma;\">Photoaging <\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<ul>\n<li><span style=\"font-family: Tahoma;\">Biology of the extracellular matrix<\/span><\/li>\n<\/ul>\n<h3><strong><span style=\"font-family: Tahoma;\">Ongoing projects:<\/span><\/strong><\/h3>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"text-decoration: underline;\"><span style=\"font-family: Tahoma;\">Area of interest 1: <\/span><\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"font-family: Tahoma;\">Exposure of the skin to sunlight is a major contributor to the pathogenesis of various different skin diseases, including skin cancer. Part of my research is aimed at further characterizing the effects of ultraviolet light on skin cells, and involves investigations on <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage signaling, cell cycling, apoptosis, <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> repair (including nucleotide excision repair, translesional <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> synthesis, and <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> recombination), and mutagenesis. A particular interest is to dissect effects of different wavelengths of the solar UV-spectrum (shortwave UVB vs. longwave UVA). <\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"font-family: Tahoma;\">With detailed <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> sequence analysis of UVA- and UVB-induced mutations, we recently reported that UVA induces mainly mutations that are typical for pyrimidine dimer-type of <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage, just like UVB, and only very few mutations typical of oxidative <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage. We hypothesize that a weaker <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage response to UVA, as compared to UVB, profoundly changes the outcome of UVA- and UVB-induced <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage, making it much more likely that a UVA-induced <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> lesion causes mutation formation, and that a UVB-induced mutation is more likely repaired correctly and thereby less likely to cause mutation formation. We have studied activation of cell cycle checkpoints, <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> repair efficiency, and apoptosis and found a profound difference between UVA- and UVB-induced responses mainly in the way how cells activate cell cycle checkpoints. We have identified several <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage response proteins (including cell cycle regulators) that are differentially activated by UVB and UVA, including ATM, Chk1, p53, p21, XPCC, FANCD2 and others. These provide the molecular markers of different <\/span><span style=\"font-family: Tahoma;\">DNA<\/span><span style=\"font-family: Tahoma;\"> damage responses to UVA and UVB, as shown functionally and by the different mutation formation outcome. These data provide good further evidence that longwave ultraviolet light (UVA) cannot be regarded safe, and that exposure to pure UVA, as e.g. in tanning studios, is dangerous.<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"text-decoration: underline;\"><span style=\"font-family: Tahoma;\">Area of interest 2: <\/span><\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"font-family: Tahoma;\">The observation of morphea (= circumscript scleroderma) in several patients that were treated with a cathepsin K inhibitor in an osteoporosis clinical trial raised my interest in a putative role of cathepsin K in skin biology. This protease has so far has only been known as the main bone-degrading protease in osteoclasts where its collagenolytic properties mediate bone degradation. We reported that it is not expressed in normal skin but in scars, and suggested a role of cathepsin K in maintaining the homeostasis of the cutaneous extracellular matrix. We also found it to be strongly expressed in melanomas and that its inhibition reduced melanoma cell invasion. These data suggest an important role of cathepsin K in melanoma invasion and metastasis. Cathepsin K was also found to be induced by ultraviolet light in dermal fibroblasts (in-vivo and in-vitro). As it is the strongest elastase in humans, it may play in major role in photoaging of skin, which is characterized by a massive degradation of dermal elastic fibers. <\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin-top: 12pt;\"><span style=\"font-family: Tahoma;\">While degradation of collagen and other extracellular matrix proteins has been widely studied in skin and other diseases, most of this research has focused on protein degradation by metalloproteinases in the extracellular space. Cathepsin K is a lysosomal protein with a very low ph optimum of 5.5. This suggests that it contributes to extracellular matrix degradation by degrading internalized extracellular matrix proteins after endocytosis. And indeed, we have been able to demonstrate internalization of extracellular collagen and elastin into lysosomes by endocytosis and a cathepsin K dependent degradation of these proteins in lysosomes. This demonstration of intracellular, as opposed to intracellular matrix degradation opens a whole new avenue to study processes of fibrosis, angiogenesis, tumor invasion and metastasis. We have also characterized signals of cathepsin K regulation and found it upregulated by IL-1 and cellular confluence, and downregulated by TGF-beta. Further characterization of receptor-mediated endocytosis of collagen is currently pursued.<\/span><\/p>\n<h3><strong><span style=\"font-family: Tahoma;\">Recent Publications:<\/span><\/strong><\/h3>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>R\u00fcnger TM and Kappes UP (2008) Mechanisms of mutation formation with long-wave ultraviolet light (UVA). <em>Photodermatology, Photoimmunology, Photomedicine <\/em>24, 2-10<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>Quintanilla-Dieck MJ, Keady M, Bhawan J, R\u00fcnger TM (2008) Role of cathepsin K in melanoma invasion.<em> Journal of Investigative Dermatology, <\/em>128, 2281 &#8211; 2288<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><a name=\"OLE_LINK1\"><\/a><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>R\u00fcnger TM (2008) Mutation formation with longwave ultraviolet light (UVA). <em>Journal of Investigative Dermatology<\/em> 128, 2138 &#8211; 2140<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<em><span> <\/span><\/em>R\u00fcnger TM (2007) How different wavelengths of the ultraviolet spectrum contribute to skin carcinogenesis \u2013 role of the cellular damage response.<span> <\/span><em>Journal of Investigative Dermatology<\/em> 127, 2103-5<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>R\u00fcnger TM, Quintanilla-Dieck MJ, Bhawan J (2007) <\/span><span style=\"font-size: 10pt; font-family: Tahoma;\">Role of cathepsin K in the turnover of the dermal extracellular matrix during scar formation. <em>Journal of Investigative Dermatology<\/em> 127, 293 &#8211; 297<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>Dunn J, Potter M, Rees A, R\u00fcnger TM (2006) Activation of the Fanconi anemia\/BRCA pathway and recombination repair in the cellular response to solar ultraviolet light. <\/span><em><span style=\"font-size: 10pt; font-family: Tahoma;\">Cancer Research<\/span><\/em><span style=\"font-size: 10pt; font-family: Tahoma;\"> 66, 11140 &#8211; 11147<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>Kappes UP, Luo D, Potter M,<span> <\/span>Schulmeister K, R\u00fcnger TM (2006) Short- and long-wave ultraviolet<strong> <\/strong>light (UVB and UVA) induce similar mutations in human skin cells. <em>Journal of Investigative Dermatology <\/em>126, 667 &#8211; 675<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>R\u00fcnger TM, Vergilis I, Sarkar-Agrawal P, DePinho RA, <\/span><span style=\"font-size: 10pt; font-family: Tahoma;\">Sharpless<\/span><span style=\"font-size: 10pt; font-family: Tahoma;\"> <\/span><span style=\"font-size: 10pt; font-family: Tahoma;\">NE<\/span><span style=\"font-size: 10pt; font-family: Tahoma;\"> (2005) How disruption of cell cycle regulating genes might predispose to sun-induced skin cancer. <em>Cell Cycle<\/em> 4, 643 \u2013 645<\/span><\/p>\n<p class=\"MsoNormal\" style=\"margin: 12pt 0pt 0.0001pt 18pt;\"><span style=\"font-size: 10pt; font-family: Tahoma;\">&#8211;<span> <\/span>Sarkar P, Vergilis I, Sharpless NE, DePinho R, R\u00fcnger TM (2004) Loss of p16<sup>INK4a<\/sup> or p19<sup>ARF<\/sup> confers deficient repair of <\/span><span style=\"font-size: 10pt; font-family: Tahoma;\">DNA<\/span><span style=\"font-size: 10pt; font-family: Tahoma;\"> photoproducts. <em>Journal of the National Cancer Institute<\/em> 96, 1790 \u2013 179 <\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Thomas M. Ruenger (R\u00fcnger), MD PhD (equiv.) Professor and Vice-Chair of Dermatology Professor of Pathology and Laboratory Medicine Department of Dermatology, Boston University School of Medicine &#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230;&#8230; Contact Info e-mail: truenger@bu.edu Education and Training: Medical Schools, University of Ulm and University of Kiel, Germany Postdoctoral Fellowship, Laboratory of Molecular Carcinogenesis, NCI, NIH Dermatology and Allergology [&hellip;]<\/p>\n","protected":false},"author":1131,"featured_media":0,"parent":3281,"menu_order":41,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/pages\/245"}],"collection":[{"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/users\/1131"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/comments?post=245"}],"version-history":[{"count":16,"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/pages\/245\/revisions"}],"predecessor-version":[{"id":14079,"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/pages\/245\/revisions\/14079"}],"up":[{"embeddable":true,"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/pages\/3281"}],"wp:attachment":[{"href":"https:\/\/www.bumc.bu.edu\/busm-pathology\/wp-json\/wp\/v2\/media?parent=245"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}