{"id":8033,"date":"2018-11-29T17:16:14","date_gmt":"2018-11-29T22:16:14","guid":{"rendered":"https:\/\/www.med.unc.edu\/pharm\/?post_type=directory&#038;p=8033"},"modified":"2025-06-12T16:06:29","modified_gmt":"2025-06-12T20:06:29","slug":"robert-a-nicholas-phd","status":"publish","type":"directory","link":"https:\/\/www.med.unc.edu\/pharm\/directory\/robert-a-nicholas-phd\/","title":{"rendered":"Robert A. Nicholas, PhD"},"content":{"rendered":"<h2><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-11601\" src=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2019\/01\/OGE-Trained-mentor-badge-webCR2-300x204.png\" alt=\"\" width=\"300\" height=\"204\" srcset=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2019\/01\/OGE-Trained-mentor-badge-webCR2-300x204.png 300w, https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2019\/01\/OGE-Trained-mentor-badge-webCR2-768x522.png 768w, https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2019\/01\/OGE-Trained-mentor-badge-webCR2-1024x696.png 1024w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/h2>\n<h2>Research Interests<\/h2>\n<ul>\n<li><b>Antibiotic Resistance in Neisseria gonorrhoeae<\/b>\n<ul>\n<li>Mechanisms of chromosomally mediated antibiotic resistance<\/li>\n<li>Biological fitness consequences of acquiring resistance to cephalosporins and compensatory mutations that increase fitness<\/li>\n<li>Development of inhibitors of lipid A biosynthesis for treatment of\u00a0<i>N. gonorrhoeae<\/i><\/li>\n<\/ul>\n<\/li>\n<li><b>P2Y Receptors<\/b><b><\/b>\n<ul>\n<li>Regulation of P2Y Receptor signaling in platelets<\/li>\n<li>Signaling mechanisms of P2Y receptors<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<h2>Research Synopsis<\/h2>\n<h3 class=\" \">Antibiotic Resistance Mechanisms<\/h3>\n<p>My laboratory is also interested in the mechanisms of antibiotic resistance in the pathogenic bacterium,\u00a0<i>Neisseria gonorrhoeae<\/i>, the etiologic agent of the sexually transmitted infection, gonorrhoea.<\/p>\n<figure class=\"thumbnail wp-caption alignleft\" style=\"width: 410px\"><a href=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2018\/11\/5d04af76-69ae-4edf-b2ad-c3338a4dc3b1.jpeg\"><img loading=\"lazy\" decoding=\"async\" class=\"image-inline somoverlay link-overlay\" title=\"GC Resistance\" src=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2018\/11\/5d04af76-69ae-4edf-b2ad-c3338a4dc3b1.jpeg\" alt=\"A diagram showing GC Resistance\" width=\"400\" height=\"300\" \/><\/a><figcaption class=\"caption wp-caption-text\">FIgure 2. GC Resistance<\/figcaption><\/figure>\n<p>In 2012, the WHO reported over 106 million gonorrhea infections worldwide. Recently, strains resistant to ceftriaxone, the last remaining effective antibiotic, have emerged, portending an era of untreatable gonorrhea. All strains with increased and full resistance to ceftriaxone contain a highly mosaic\u00a0<i>penA<\/i>\u00a0gene encoding penicillin-binding protein 2 (PBP2), the lethal target of ceftriaxone, with up to 70 amino acid mutations. Other mutations include mtrR, which increases expression of an efflux pump, and penB, which encodes mutations in the major outer membrane porin, PIB (fig. 2).<\/p>\n<p>We are investigating the structural mechanisms of resistance of PBP2, how the presence of a highly altered PBP2 impacts biological fitness and pathogenesis, and identifying compensatory mutations arising in the mouse model of gonococcal infection that increase fitness of mosaic\u00a0<i>penA<\/i>-containing strains.<\/p>\n<h3>Platelet P2Y Receptor Regulation<b><\/b><\/h3>\n<figure class=\"thumbnail wp-caption alignleft\" style=\"width: 290px\"><a href=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2018\/11\/9656c773-97b1-4601-af47-d03281165cb4.jpeg\"><img loading=\"lazy\" decoding=\"async\" class=\"somoverlay image-left link-overlay\" title=\"Figure 1 \" src=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2018\/11\/9656c773-97b1-4601-af47-d03281165cb4.jpeg\" alt=\"A diagram of Platelet P2Y Receptor Regulation\" width=\"280\" height=\"400\" data-wp-editing=\"1\" \/><\/a><figcaption class=\"caption wp-caption-text\">Figure 1. Diagram of the simultaneous activation of P2Y1 and P2Y12 receptors leading to platelet aggregation.<\/figcaption><\/figure>\n<p>P2Y receptors are important receptors in platelet biology. When platelets come in contact with underlying tissue following disruption of the blood vessel, they release dense granules containing secondary mediators, resulting in aggregation of passing platelets and formation of a platelet plug. One of the most important of these mediators is ADP, which acts on two P2Y receptors: P2Y<sub>1<\/sub>\u00a0and P2Y<sub>12<\/sub>. The P2Y<sub>1<\/sub>\u00a0receptor couples to Gq, mobilizes intracellular Ca<sup>2+<\/sup>, and activates PKC, whereas the P2Y<sub>12<\/sub>\u00a0receptor couples to Gi and inhibition of adenylyl cyclase (the P2Y<sub>12<\/sub>receptor is the target of the anti-platelet drug Plavix). Simultaneous activation of these two receptors is required for aggregation (Fig. 1). The P2Y<sub>1<\/sub>\u00a0receptor is uniquely regulated and rapidly desensitizes (t<sub>1\/2<\/sub>\u00a0of ~18 sec), preventing further aggregation. We are investigating the molecular mechanisms of this rapid desensitization in both a mouse transplantation model and knock-in mice expressing a non-desensitizing receptor mutant receptor.<\/p>\n<div><span style=\"color: inherit;font-size: 30px\">Publications<\/span><\/div>\n<div>\n<p><strong><a class=\"external-link\" title=\"\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/sites\/myncbi\/10ap9uOKouf\/bibliography\/40331898\/public\/?sort=date&amp;direction=descending\" rel=\"noopener\">View complete list of publications in NCBI library<\/a><\/strong><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Research Interests Antibiotic Resistance in Neisseria gonorrhoeae Mechanisms of chromosomally mediated antibiotic resistance Biological fitness consequences of acquiring resistance to cephalosporins and compensatory mutations that increase fitness Development of inhibitors of lipid A biosynthesis for treatment of\u00a0N. gonorrhoeae P2Y Receptors Regulation of P2Y Receptor signaling in platelets Signaling mechanisms of P2Y receptors Research Synopsis Antibiotic &hellip; <a href=\"https:\/\/www.med.unc.edu\/pharm\/directory\/robert-a-nicholas-phd\/\" aria-label=\"Read more about Robert A. Nicholas, PhD\">Read more<\/a><\/p>\n","protected":false},"featured_media":23038,"template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"class_list":["post-8033","directory","type-directory","status-publish","has-post-thumbnail","hentry","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Robert A. Nicholas, PhD | 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\/robert-a-nicholas-phd\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Robert A. Nicholas, PhD | Pharmacology\" \/>\n<meta property=\"og:description\" content=\"Research Interests Antibiotic Resistance in Neisseria gonorrhoeae Mechanisms of chromosomally mediated antibiotic resistance Biological fitness consequences of acquiring resistance to cephalosporins and compensatory mutations that increase fitness Development of inhibitors of lipid A biosynthesis for treatment of\u00a0N. gonorrhoeae P2Y Receptors Regulation of P2Y Receptor signaling in platelets Signaling mechanisms of P2Y receptors Research Synopsis Antibiotic &hellip; Read more\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.med.unc.edu\/pharm\/directory\/robert-a-nicholas-phd\/\" \/>\n<meta property=\"og:site_name\" content=\"Pharmacology\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/UNC-Pharmacology-693103474191364\/\" \/>\n<meta property=\"article:modified_time\" content=\"2025-06-12T20:06:29+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.med.unc.edu\/pharm\/wp-content\/uploads\/sites\/930\/2018\/11\/Rob_Nicholas-400x520-1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"400\" \/>\n\t<meta property=\"og:image:height\" content=\"520\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.med.unc.edu\/pharm\/directory\/robert-a-nicholas-phd\/\",\"url\":\"https:\/\/www.med.unc.edu\/pharm\/directory\/robert-a-nicholas-phd\/\",\"name\":\"Robert A. 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Nicholas, PhD"],"_upd_reverse_display_name":["Nicholas, Robert"],"_upd_last_name":["Nicholas"],"_upd_first_name":["Robert"],"_upd_sortorder_override":[],"_upd_sortorder":["1"],"_upd_gallery_summary":["<strong>Professor and Vice Chair, Research and Education<\/strong>\r\nResearch: Signaling mechanisms of G protein-coupled P2Y receptors; antibiotic resistance mechanisms\r\nOffice: 4046 GMB\r\nPhone: <a href=\"tel:9199666547\">(919) 966-6547<\/a>\r\n<a href=\"https:\/\/www.med.unc.edu\/pharm\/nicholaslab\/\">Lab Website<\/a>\r\n<a href=\"mailto:nicholas@med.unc.edu\">Email<\/a>"],"_upd_no_link":[],"_upd_degree1":["PhD"],"_upd_degree2":[],"_upd_email":[[{"email_text":"nicholas@med.unc.edu"}]],"_upd_phone":[[{"phone_text":"919-966-6547","phone_type":"Office Phone"}]],"_upd_address":[[{"address":{"address-1":"120 Mason Farm Rd.","address-2":"4046 Genetic Medicine","campus-box":"CB # 7365","city":"Chapel Hill","state":"NC","zip":"27599-7365"}}]],"_links":{"self":[{"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory\/8033","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory"}],"about":[{"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/types\/directory"}],"version-history":[{"count":1,"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory\/8033\/revisions"}],"predecessor-version":[{"id":23039,"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory\/8033\/revisions\/23039"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/media\/23038"}],"wp:attachment":[{"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/media?parent=8033"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}