{"id":8091,"date":"2018-12-04T11:18:58","date_gmt":"2018-12-04T16:18:58","guid":{"rendered":"https:\/\/www.med.unc.edu\/pharm\/?post_type=directory&#038;p=8091"},"modified":"2025-06-12T14:09:18","modified_gmt":"2025-06-12T18:09:18","slug":"nicholas-g-brown","status":"publish","type":"directory","link":"https:\/\/www.med.unc.edu\/pharm\/directory\/nicholas-g-brown\/","title":{"rendered":"Nicholas G. Brown, 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>Cell cycle, mitosis, ubiquitin ligases, anaphase promoting complex<\/li>\n<\/ul>\n<h2>Research Synopsis<\/h2>\n<p>The overarching goal of my research program is to understand the system of inter- and intra-molecular interactions that dynamically regulate the catalytic mechanisms of enzymes to precisely time the events of the cell cycle.\u00a0 We employ a hybrid technological approach, including enzyme kinetics, mutagenesis, X-ray crystallography, NMR spectroscopy, and cryo-EM, to characterize these molecular machines.\u00a0 Our results provide mechanistic insight into the cell cycle that will influence the drug design of cancer therapeutics.<\/p>\n<div class=\"entry-content-asset\"><iframe loading=\"lazy\" title=\"Animation: Interplay of APC\/C, UBE2S, UBE2C &amp; ubiquitinate substrate in rapid cell cycle transitions\" width=\"560\" height=\"315\" src=\"https:\/\/www.youtube.com\/embed\/PZj-RemO4mM?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><\/div>\n<p>UBE2S stimulates APC\/C-UBE2C activity via a positive allosteric feedback to increase the levels of its own substrate (primed substrates). Consequently, UBE2S can then elongate ubiquitin chains in Ub-substrates. Overall, this increases the efficiency of substrate ubiquitination and substrate targeting for proteasomal degradation. We hypothesize this interplay between APC\/C, UBE2C, and UBE2S is one of the aspects that help during rapid cell cycle transitions. For example, at the beginning of mitosis the MCC suppresses APC\/C activity until the spindle checkpoint is satisfied. During this suppressing effect, the binding site of UBE2S on the APC\/C is still available. Once the spindle checkpoint is satisfied, UBE2S bound to the APC\/C boosts APC\/C-UBE2C activity, degradation of key main substrates occurs, chromosomal segregation occurs, and finally mitosis is completed (shown as the finish line). ~Animation by Alejandro R. Martinez Chacin. Martinez-Chacin RC et al.\u00a0<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32393902\/?from_term=brown+ng&amp;from_sort=date&amp;from_pos=1\" target=\"_blank\" rel=\"noopener noreferrer\" data-auth=\"NotApplicable\">Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC\/C for substrate priming.\u00a0<\/a><i>Nat Struct Mol Biol.<\/i>\u00a02020 Jun;27(6):550-560.<\/p>\n<h2>Publications<\/h2>\n<p><strong><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/myncbi\/1HWZ79-Rlrhkc\/bibliography\/public\/\">View complete list of publications on NCBI bibliography<\/a><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Research Interests Cell cycle, mitosis, ubiquitin ligases, anaphase promoting complex Research Synopsis The overarching goal of my research program is to understand the system of inter- and intra-molecular interactions that dynamically regulate the catalytic mechanisms of enzymes to precisely time the events of the cell cycle.\u00a0 We employ a hybrid technological approach, including enzyme kinetics, &hellip; <a href=\"https:\/\/www.med.unc.edu\/pharm\/directory\/nicholas-g-brown\/\" aria-label=\"Read more about Nicholas G. Brown, PhD\">Read more<\/a><\/p>\n","protected":false},"featured_media":3422,"template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","_links_to":"","_links_to_target":""},"class_list":["post-8091","directory","type-directory","status-publish","has-post-thumbnail","hentry","odd"],"acf":[],"_upd_display_name":["Nicholas G. Brown, PhD "],"_upd_reverse_display_name":["Brown, Nicholas"],"_upd_last_name":["Brown"],"_upd_first_name":["Nicholas"],"_upd_sortorder_override":[],"_upd_sortorder":["1"],"_upd_gallery_summary":["<strong>Associate Professor<\/strong>\r\n<span style=\"background-color: #007fae;color: #fff\">Accepting Rotation Students<\/span>\r\nResearch: Cell cycle, mitosis, ubiquitin ligases, anaphase promoting complex\r\nOffice: 4062 GMB\r\nPhone: <a href=\"tel:9199661235\">(919) 966-1235<\/a>\r\n<a href=\"https:\/\/www.med.unc.edu\/pharm\/brownlab\/\" rel=\"noopener\">Lab Website<\/a>\r\n<a href=\"mailto:nbrown1@email.unc.edu\">Email<\/a>"],"_upd_no_link":[],"_upd_degree1":["PhD"],"_upd_degree2":[],"_upd_email":[[{"email_text":"nbrown1@email.unc.edu"}]],"_upd_phone":[[{"phone_text":"919-966-1235","phone_type":"Office Phone"}]],"_upd_address":[[{"address":{"address-1":"4062 Genetic Medicine Bldg.","address-2":"","campus-box":"CB #7365","city":"Chapel Hill","state":"NC","zip":"27599"}}]],"_links":{"self":[{"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory\/8091","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":2,"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory\/8091\/revisions"}],"predecessor-version":[{"id":25287,"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/directory\/8091\/revisions\/25287"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/media\/3422"}],"wp:attachment":[{"href":"https:\/\/www.med.unc.edu\/pharm\/wp-json\/wp\/v2\/media?parent=8091"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}