{"id":81,"date":"2023-01-11T18:33:55","date_gmt":"2023-01-11T18:33:55","guid":{"rendered":"https:\/\/labs.icahn.mssm.edu\/whitelab\/?page_id=81"},"modified":"2024-12-16T15:13:48","modified_gmt":"2024-12-16T15:13:48","slug":"research","status":"publish","type":"page","link":"https:\/\/labs.icahn.mssm.edu\/whitelab\/research\/","title":{"rendered":"Research"},"content":{"rendered":"<p>[et_pb_section fb_built=&#8221;1&#8243; fullwidth=&#8221;on&#8221; admin_label=&#8221;Page Header&#8221; _builder_version=&#8221;4.9.0&#8243; background_image=&#8221;https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-content\/uploads\/sites\/433\/2023\/01\/business-12.jpg&#8221; parallax=&#8221;on&#8221; animation_direction=&#8221;top&#8221;][et_pb_fullwidth_header title=&#8221;Research Initiatives&#8221; text_orientation=&#8221;center&#8221; admin_label=&#8221;Hero Section&#8221; _builder_version=&#8221;4.9.0&#8243; title_font=&#8221;Montserrat|on|||&#8221; title_font_size=&#8221;60px&#8221; title_line_height=&#8221;1.4em&#8221; content_font_size=&#8221;22px&#8221; content_line_height=&#8221;1.8em&#8221; subhead_font=&#8221;||||&#8221; background_color=&#8221;rgba(255, 255, 255, 0)&#8221; use_background_color_gradient=&#8221;on&#8221; background_color_gradient_start=&#8221;rgba(58,52,226,0.93)&#8221; background_color_gradient_end=&#8221;rgba(73,108,220,0.7)&#8221; background_image=&#8221;https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-content\/uploads\/sites\/433\/2023\/03\/20220806_20012311008-scaled.jpg&#8221; background_size=&#8221;initial&#8221; background_position=&#8221;top_left&#8221; background_repeat=&#8221;repeat&#8221; custom_button_one=&#8221;on&#8221; button_one_text_size=&#8221;16px&#8221; button_one_bg_color=&#8221;#6eba01&#8243; button_one_border_width=&#8221;2px&#8221; button_one_border_color=&#8221;#6eba01&#8243; button_one_letter_spacing=&#8221;2&#8243; button_one_font=&#8221;Montserrat|||on|&#8221; button_one_use_icon=&#8221;off&#8221; custom_button_two=&#8221;on&#8221; button_two_text_size=&#8221;16px&#8221; button_two_border_width=&#8221;2px&#8221; button_two_border_color=&#8221;#ffffff&#8221; button_two_letter_spacing=&#8221;2&#8243; button_two_font=&#8221;Montserrat|||on|&#8221; button_two_use_icon=&#8221;off&#8221; module_alignment=&#8221;left&#8221; animation_style=&#8221;fade&#8221; button_one_text_color_hover=&#8221;#6eba01&#8243; button_two_text_color_hover=&#8221;#6eba01&#8243; button_one_border_color_hover=&#8221;#ffffff&#8221; button_two_border_color_hover=&#8221;#ffffff&#8221; button_one_border_radius_hover=&#8221;0&#8243; button_two_border_radius_hover=&#8221;0&#8243; button_one_letter_spacing_hover=&#8221;2&#8243; button_two_letter_spacing_hover=&#8221;2&#8243; button_one_bg_color_hover=&#8221;#ffffff&#8221; button_two_bg_color_hover=&#8221;#ffffff&#8221; button_one_text_size__hover_enabled=&#8221;off&#8221; button_two_text_size__hover_enabled=&#8221;off&#8221; button_one_text_color__hover_enabled=&#8221;on&#8221; button_one_text_color__hover=&#8221;#6eba01&#8243; button_two_text_color__hover_enabled=&#8221;on&#8221; button_two_text_color__hover=&#8221;#6eba01&#8243; button_one_border_width__hover_enabled=&#8221;off&#8221; button_two_border_width__hover_enabled=&#8221;off&#8221; button_one_border_color__hover_enabled=&#8221;on&#8221; button_one_border_color__hover=&#8221;#ffffff&#8221; button_two_border_color__hover_enabled=&#8221;on&#8221; button_two_border_color__hover=&#8221;#ffffff&#8221; button_one_border_radius__hover_enabled=&#8221;on&#8221; button_one_border_radius__hover=&#8221;0&#8243; button_two_border_radius__hover_enabled=&#8221;on&#8221; button_two_border_radius__hover=&#8221;0&#8243; button_one_letter_spacing__hover_enabled=&#8221;on&#8221; button_one_letter_spacing__hover=&#8221;2&#8243; button_two_letter_spacing__hover_enabled=&#8221;on&#8221; button_two_letter_spacing__hover=&#8221;2&#8243; button_one_bg_color__hover_enabled=&#8221;on&#8221; button_one_bg_color__hover=&#8221;#ffffff&#8221; button_two_bg_color__hover_enabled=&#8221;on&#8221; button_two_bg_color__hover=&#8221;#ffffff&#8221;]<\/p>\n<p>Check out below the current research topics that we are exploring.<\/p>\n<p>&nbsp;<\/p>\n<p>[\/et_pb_fullwidth_header][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;][et_pb_row column_structure=&#8221;1_2,1_2&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;][et_pb_blurb title=&#8221;Viral-Host Interactions&#8221; image=&#8221;https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-content\/uploads\/sites\/433\/2023\/02\/D8-20X-PL-FL-Phase_GFP-469525DAPI-377447_1_001-smaller.jpeg&#8221; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221; transform_origin=&#8221;256%|160%&#8221;]<\/p>\n<p><span data-contrast=\"auto\" xml:lang=\"EN-US\" lang=\"EN-US\" class=\"TextRun Highlight SCXW170311748 BCX0\"><span class=\"NormalTextRun SCXW170311748 BCX0\">During a viral infection, viruses <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">can<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> hijack the host machinery <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">to <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">enhance <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">their <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">replication and<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> counteract host defenses.<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> By identifying the host factors that the virus utilize<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">s<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> we can develop or repurpose drugs to negate the virus-host interaction, allowing for the cell to better defend and impede viral replication. In our analysis of SARS-CoV-2 virus-host interactions <\/span><span class=\"NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW170311748 BCX0\">we<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> i<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">n cooperation with the <a href=\"https:\/\/kroganlab.ucsf.edu\/krogan-lab\" target=\"_blank\" rel=\"noopener noreferrer\" title=\"Nevan Krogan Lab Website Link\">Nevan <\/a><\/span><a href=\"https:\/\/kroganlab.ucsf.edu\/krogan-lab\" target=\"_blank\" rel=\"noopener noreferrer\" title=\"Nevan Krogan Lab Website Link\"><span class=\"NormalTextRun SpellingErrorV2Themed SCXW170311748 BCX0\">Krogan<\/span><\/a><span class=\"NormalTextRun SCXW170311748 BCX0\"><a href=\"https:\/\/kroganlab.ucsf.edu\/krogan-lab\" target=\"_blank\" rel=\"noopener noreferrer\" title=\"Nevan Krogan Lab Website Link\"> Lab<\/a>, have identified 332 host factors important for its infection<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">. With these findings we were able to identify host-targeted <\/span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW170311748 BCX0\">plitidepsin<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">, already <\/span><span class=\"NormalTextRun ContextualSpellingAndGrammarErrorV2Themed SCXW170311748 BCX0\">clinically-approved<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> treatment for multiple myeloma, as a SARS-CoV-2 therapeutic. The White lab continues to explore host-virus interactions in SARS-CoV-2 and Influenza virus to better develop and identify <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">new <\/span><span class=\"NormalTextRun SCXW170311748 BCX0\">therapeutic<\/span><span class=\"NormalTextRun SCXW170311748 BCX0\"> treatments.<\/span><\/span><span class=\"EOP SCXW170311748 BCX0\" data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}\">\u00a0<\/span><\/p>\n<p>[\/et_pb_blurb][\/et_pb_column][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;][et_pb_blurb title=&#8221;Cell Culture &amp; In-Vivo Models&#8221; image=&#8221;https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-content\/uploads\/sites\/433\/2023\/01\/20230117_130951-smaller.jpg&#8221; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221; locked=&#8221;off&#8221;]<\/p>\n<p><span data-contrast=\"auto\" xml:lang=\"EN-US\" lang=\"EN-US\" class=\"TextRun SCXW250602983 BCX0\"><span class=\"NormalTextRun SCXW250602983 BCX0\">The White lab <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">has a dedicated Tecan D300e and <\/span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW250602983 BCX0\">Biomek<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> i7 to automate our cell culture systems and screen antiviral drugs in high throughput<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> formats<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">. <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">Cell culture models are critical<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> in the development of antiviral therapeutics. Screening of antiviral <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">drugs in standard cell lines that can be infected <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">by the target virus<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> is a ubiquitous early stage of drug development<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">. We <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">also <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">use these cell lines for <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">initial screening, but <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">these cell lines are plagued with genomic abnormalities that reduce their relevance to<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> the human host. Therefore, we employ primary<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> (HAE on ALI)<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> and primary-like <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">(iPSC) <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">models for advanced analysis of antiviral leads to <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">quantify the efficacy of the compound accurately.<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">We have also established animal models <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">of viral infection for the analysis of antiviral drugs for coronaviruses, flaviviruses and enteroviruses. Therefore, the White lab <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">encompasses<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">all<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> the<\/span><span class=\"NormalTextRun SCXW250602983 BCX0\"> critical preclinical analysis <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">required <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">to determine antiviral efficacy of <\/span><span class=\"NormalTextRun SCXW250602983 BCX0\">therapeutic candidates.<\/span><\/span><span class=\"EOP SCXW250602983 BCX0\" data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}\">\u00a0<\/span><\/p>\n<p>[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=&#8221;1_2,1_2&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;0px|||||&#8221;][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;][et_pb_blurb title=&#8221;Drug Combination Studies&#8221; image=&#8221;https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-content\/uploads\/sites\/433\/2023\/02\/D8-40X-PL-FL-Phase_GFP-469525DAPI-377447_1_001-smaller.jpeg&#8221; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;]<\/p>\n<p><span data-contrast=\"auto\" xml:lang=\"EN-US\" lang=\"EN-US\" class=\"TextRun Highlight SCXW120674412 BCX0\"><span class=\"NormalTextRun SCXW120674412 BCX0\">Antiviral drug<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> combination therapies have been <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">remarkably <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">effective<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> in the clinic<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> against<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">HIV (H<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">uman<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">Immunodeficiency<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> V<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">irus<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">)<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> and <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">HCV (hepatitis C virus)<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">. <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">These <\/span><\/span><span data-contrast=\"auto\" xml:lang=\"EN-US\" lang=\"EN-US\" class=\"TextRun SCXW120674412 BCX0\"><span class=\"NormalTextRun SCXW120674412 BCX0\">chronic viral infections<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> necessitate the use of drug combination<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">s to prevent the inevitable emergence of resistance from monotherapy antiviral strategies.<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> Acute viral infections, like those established by<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> many<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> respiratory viruses, <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">also<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> are<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> at high risk of the development of antiviral resistance. This is due to the high mutation rate of RNA viruses, which <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">leads to the constant development of viral variants.<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><\/span><span data-contrast=\"auto\" xml:lang=\"EN-US\" lang=\"EN-US\" class=\"TextRun Highlight SCXW120674412 BCX0\"><span class=\"NormalTextRun SCXW120674412 BCX0\">Furthermore<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">, the use of a single drug in the treatment of an infection could necessitate the use of a high dos<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">age<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">resulting<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> in<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">increase<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">d<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">toxicity<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">.<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">The use of two drugs targeting different viral <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">proteins <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">allows for each drug in the combination to inhibit the replication <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">of viruses resistant to the partner drug.<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> <\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">T<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">he White lab continues to explore the mechanism<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\">s<\/span><span class=\"NormalTextRun SCXW120674412 BCX0\"> behind synergistic drug interactions and assess potential clinical candidates that can take advantage of this antiviral synergy to improve potency and prevent the development of resistance in the clinic for Coronavirus, Flavivirus and Enterovirus<\/span><\/span><span data-contrast=\"auto\" xml:lang=\"EN-US\" lang=\"EN-US\" class=\"TextRun SCXW120674412 BCX0\"><span class=\"NormalTextRun SCXW120674412 BCX0\">.\u00a0<\/span><\/span><span class=\"EOP SCXW120674412 BCX0\" data-ccp-props=\"{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}\">\u00a0<\/span><\/p>\n<p>[\/et_pb_blurb][\/et_pb_column][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;][et_pb_blurb title=&#8221;Antiviral Resistance Analysis&#8221; image=&#8221;https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-content\/uploads\/sites\/433\/2023\/01\/IMG-0559-rotated.jpg&#8221; _builder_version=&#8221;4.9.0&#8243; _module_preset=&#8221;default&#8221;]<\/p>\n<p><span class=\"NormalTextRun SCXW61299366 BCX0\">Antiviral resistance is <\/span><span class=\"NormalTextRun SCXW61299366 BCX0\">a prominent concept in the development of antiviral drugs. This is because the mutational rate <\/span><span class=\"NormalTextRun SCXW61299366 BCX0\">of viruses is orders of magnitude larger than other pathogens such as bacteria and parasites.<\/span><span class=\"NormalTextRun SCXW61299366 BCX0\"> Therefore, the potential for an antiviral drug to generate resistance mutations<\/span><span class=\"NormalTextRun SCXW61299366 BCX0\"> in a viral population is <\/span><span class=\"NormalTextRun SCXW61299366 BCX0\">a critical step in the development of novel therapeutics. The <\/span><span class=\"NormalTextRun SCXW61299366 BCX0\">W<\/span><span class=\"NormalTextRun SCXW61299366 BCX0\">hite lab uses automated NGS<\/span><span class=\"NormalTextRun SCXW61299366 BCX0\"> library preparation and analysis to track antiviral resistance mutations under compound selective<\/span><span class=\"NormalTextRun SCXW61299366 BCX0\"> pressure in our cell culture and animal models.<\/span><\/p>\n<p>[\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Check out below the current research topics that we are exploring. &nbsp;During a viral infection, viruses can hijack the host machinery to enhance their replication and counteract host defenses. By identifying the host factors that the virus utilizes we can develop or repurpose drugs to negate the virus-host interaction, allowing for the cell to better [&hellip;]<\/p>\n","protected":false},"author":576,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-81","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/pages\/81","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/users\/576"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/comments?post=81"}],"version-history":[{"count":12,"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/pages\/81\/revisions"}],"predecessor-version":[{"id":292,"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/pages\/81\/revisions\/292"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/whitelab\/wp-json\/wp\/v2\/media?parent=81"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}