{"id":8505,"date":"2019-01-17T13:07:11","date_gmt":"2019-01-17T18:07:11","guid":{"rendered":"https:\/\/www.med.unc.edu\/pharm\/?post_type=directory&#038;p=8505"},"modified":"2022-07-13T17:12:48","modified_gmt":"2022-07-13T21:12:48","slug":"h-shelton-earp-iii-md","status":"publish","type":"directory","link":"https:\/\/www.med.unc.edu\/pharm\/directory\/h-shelton-earp-iii-md\/","title":{"rendered":"H. Shelton Earp, III, MD"},"content":{"rendered":"<h2>Research Interests<\/h2>\n<ul>\n<li>EGF receptor family<\/li>\n<li>HER4\/ErbB4: growth inhibition and differentiation \u2013 Breast Cancer<\/li>\n<li>Mer receptor tyrosine kinase signaling \u2013 Leukemia and Tumor Immunology<\/li>\n<li>Ack1 receptor tyrosine kinase signaling \u2013 Prostate Cancer<\/li>\n<\/ul>\n<h2>Research Synopsis<\/h2>\n<p>Our lab is interested in how signals from membrane receptors are transduced to the nucleus altering gene expression, cell shape, proliferation and differentiation. We are particularly interested in tyrosine-specific protein kinases in breast and prostate cancer, as well as lymphoma\/leukemia. One project studies a family of transmembrane tyrosine kinases, the EGF receptor and related molecules, HER2, HER3 and HER4. We are trying to identify distinctive substrates and pathways for these receptors in order to understand how they produce functional differences; for example, in breast cancer cells, EGF receptor or HER2 activation stimulates growth, whereas activation of specific HER4 isoforms triggers differentiation. We have developed HER4 isoform specific, Tet inducible mouse models with which to study HER4\u2019s disparate actions.<\/p>\n<p>A second project investigates a novel transmembrane tyrosine kinase, Mer, cloned and sequenced in our lab. Mer is normally expressed in monocytes, as well as in epithelial and reproductive tissue (including prostate). It is not expressed in normal B or T lymphocytes. However, 60% of childhood, lymphatic leukemias express Mer, including a subpopulation of childhood leukemias derived from very early T cell precursors. We have shown that Mer has anti-apoptotic and cytoskeletal regulatory actions when expressed in mouse leukemic cell lines. We are attempting to define the mechanism by which a tyrosine kinase sends anti-apoptotic signals without stimulating proliferation and how it results in chemoresistance in leukemia and other cancer cells. We are collaborating with Stephen Frye to develop small molecule, Mer TK inhibitors as in vivo chemical biologic probes and eventually as drugs for childhood leukemia.\u00a0We are also investigating the role of Mer in tumor associated macrophages and their role in breast cancer.<\/p>\n<p>Lastly, we have shown that Mer and other RTKs can activate an intracellular tyrosine kinase, Ack1.\u00a0In turn, Ack1 tyrosine phosphorylates the androgen receptor (AR) on tyrosine 267, converting the AR into an androgen independent transcription factor.\u00a0Ack1 activation leads to enhanced, androgen independent cell line tumorigenesis as well as invasion. We have shown that transgenic mouse models expressing activated Ack develop prostate neoplasia.\u00a0We are defining the substrates and biologic actions that mediate Ack1-dependent cell survival and invasive behaviors.<\/p>\n<h2>Publications<\/h2>\n<p><a class=\"external-link\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/sites\/entrez?Db=pubmed&amp;Cmd=DetailsSearch&amp;Term=Earp+HS%5Bauthor%5D\" rel=\"noopener\"><strong>View complete list of publications in Pubmed<\/strong><br \/>\n<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Research Interests EGF receptor family HER4\/ErbB4: growth inhibition and differentiation \u2013 Breast Cancer Mer receptor tyrosine kinase signaling \u2013 Leukemia and Tumor Immunology Ack1 receptor tyrosine kinase signaling \u2013 Prostate Cancer Research Synopsis Our lab is interested in how signals from membrane receptors are transduced to the nucleus altering gene expression, cell shape, proliferation and &hellip; <a href=\"https:\/\/www.med.unc.edu\/pharm\/directory\/h-shelton-earp-iii-md\/\" aria-label=\"Read more about H. Shelton Earp, III, MD\">Read more<\/a><\/p>\n","protected":false},"featured_media":8506,"template":"","meta":{"_acf_changed":false,"_links_to":"","_links_to_target":""},"class_list":["post-8505","directory","type-directory","status-publish","has-post-thumbnail","hentry","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.9 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>H. Shelton Earp, III, MD | Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/pharm\/directory\/h-shelton-earp-iii-md\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"H. 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