{"id":76,"date":"2023-10-20T10:25:35","date_gmt":"2023-10-20T17:25:35","guid":{"rendered":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/?page_id=76"},"modified":"2025-10-27T12:26:53","modified_gmt":"2025-10-27T19:26:53","slug":"research","status":"publish","type":"page","link":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/research\/","title":{"rendered":"Research"},"content":{"rendered":"<div  class='flex_column av-1bkbs-d08aea77265796ccccabcb94bffe1637 av_one_full  avia-builder-el-0  el_before_av_heading  avia-builder-el-first  first flex_column_div  '     ><p>\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3dld67-8bcab9075885b137d6a047f8ad44f362\">\n#top .av-special-heading.av-lo3dld67-8bcab9075885b137d6a047f8ad44f362{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lo3dld67-8bcab9075885b137d6a047f8ad44f362 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lo3dld67-8bcab9075885b137d6a047f8ad44f362 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lo3dld67-8bcab9075885b137d6a047f8ad44f362 av-special-heading-h2 blockquote modern-quote  avia-builder-el-1  el_before_av_textblock  avia-builder-el-first '><h2 class='av-special-heading-tag '  itemprop=\"headline\"  >Our Research<\/h2><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div><br \/>\n<section  class='av_textblock_section av-lnyvmud1-16e9785c42dcdf5234f98ee1350a8813 '   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock'  itemprop=\"text\" ><p>We study the ecological and evolutionary dynamics of infectious disease in animal and human populations, with emphasis on zoonotic and emerging pathogens. By combining theoretical models and data, we aim to deepen our understanding of fundamental principles of disease transmission and adaptation, and apply those principles to interpret observed patterns, uncover driving mechanisms, and design effective control policies.<\/p>\n<p>Zoonoses &#8212; i.e. diseases that transmit from animals to humans &#8212; account for over 60% of all human pathogens and 75% of emerging pathogens, but key aspects of zoonotic disease dynamics remain poorly understood. We have projects focusing on each phase of the zoonotic emergence process:<\/p>\n<ul>\n<li>Dynamics of zoonotic infections in their wildlife reservoirs<\/li>\n<li>Spillover transmission from animals to humans<\/li>\n<li>Outbreak dynamics of newly introduced pathogens<\/li>\n<li>Adaptation of pathogens to new host species<\/li>\n<\/ul>\n<p>This work spans a range of pathogen-host systems, including leptospirosis in California sea lions, mpox at the wildlife-human interface, and influenza and other emerging diseases in human populations. There are also several conceptual themes running throughout the work, including the impact of host heterogeneities and superspreading on disease dynamics and control, and the integration of mechanisms across disciplines and across scales of biological organization.<\/p>\n<h4>The need for integration<\/h4>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-77 alignnone\" src=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph.png\" alt=\"\" width=\"677\" height=\"261\" srcset=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph.png 1576w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph-300x116.png 300w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph-1030x397.png 1030w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph-768x296.png 768w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph-1536x593.png 1536w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph-1500x579.png 1500w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/graph-705x272.png 705w\" sizes=\"auto, (max-width: 677px) 100vw, 677px\" \/><\/p>\n<p>Our review of all published models of zoonotic disease transmission <a href=\"http:\/\/www.sciencemag.org\/content\/326\/5958\/1362.abstract\" target=\"_blank\" rel=\"noopener\"> published in Science<\/a> showed that the field suffers from a marked lack of integration (see figure). Very few modeling studies bring together the animal and human components of zoonotic transmission, to focus on cross-species spillover transmission or the \u2018stuttering chains\u2019 of transmission that occur when a pathogen transmits weakly between humans. Models that integrate pathogen evolution alongside transmission dynamics have also been rare. In fact, most modeling studies have focused on a single phase of the process, missing out on the essential cross-species nature of zoonotic infections \u2013 this is especially true for directly-transmitted pathogens such as influenza or mpox. There has also been too little integration across the many disciplines that influence disease dynamics at individual, population and global scales.<\/p>\n<p>Our lab\u2019s work aims to address this gap in integrative research, by pursuing five major projects that overlap to span all phases of the zoonotic emergence process.<\/p>\n<ul>\n<li><a href=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/research\/#lepto\">Leptospirosis in California sea lions and other wildlife species<\/a><\/li>\n<li><a href=\"#zoonosis\">Cross-scale models of zoonotic viruses (including SARS-CoV-2)<\/a><\/li>\n<li><a href=\"https:\/\/faculty.eeb.ucla.edu\/lloydsmith\/research\/#influenza\">Childhood hemagglutinin imprinting to influenza A viruses<\/a><\/li>\n<li><a href=\"#monkeypox\">Mpox emergence in the Democratic Republic of Congo<\/a><\/li>\n<li><a href=\"#evolution\">Cross-scale models for evolutionary emergence of novel pathogens<\/a><\/li>\n<\/ul>\n<p>By working on these projects in parallel, we identify common themes in zoonotic disease dynamics and benefit from cross-pollination between systems, as ideas from one study help to solve problems in another.<\/p>\n<\/div><\/section><\/p><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lnyvnbp9-464f0c070104c90f947e7391d96cab5f\">\n#top .av-special-heading.av-lnyvnbp9-464f0c070104c90f947e7391d96cab5f{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lnyvnbp9-464f0c070104c90f947e7391d96cab5f .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lnyvnbp9-464f0c070104c90f947e7391d96cab5f .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lnyvnbp9-464f0c070104c90f947e7391d96cab5f av-special-heading-h3 blockquote classic-quote classic-quote-left  avia-builder-el-3  el_after_av_one_full  el_before_av_heading '><h3 class='av-special-heading-tag '  itemprop=\"headline\"  >Our Major Projects<\/h3><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3dn8mz-cadf7bf9a4c61d5dad16fa5c9386a200\">\n#top .av-special-heading.av-lo3dn8mz-cadf7bf9a4c61d5dad16fa5c9386a200{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lo3dn8mz-cadf7bf9a4c61d5dad16fa5c9386a200 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lo3dn8mz-cadf7bf9a4c61d5dad16fa5c9386a200 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lo3dn8mz-cadf7bf9a4c61d5dad16fa5c9386a200 av-special-heading-h4  avia-builder-el-4  el_after_av_heading  el_before_av_three_fourth '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >Leptospirosis in California sea lions and other wildlife species<\/h4><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n<div  class='flex_column av-6c4po-56df63e6dca8c0981af8f280072d1e80 av_three_fourth  avia-builder-el-5  el_after_av_heading  el_before_av_one_fourth  first flex_column_div  '     ><section  class='av_textblock_section av-lnyvtspi-f4af82b2e115e2d9e7436421e8ecc016 '   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock'  itemprop=\"text\" ><p><a name=\"lepto\"><\/a><\/p>\n<h5><\/h5>\n<h5 style=\"padding-left: 40px\"><\/h5>\n<p style=\"padding-left: 40px\">Leptospirosis is thought to be the most widespread zoonotic disease in the world, and it imposes a high health burden in humans, wildlife and livestock worldwide. Yet there are many open questions about how the bacteria that cause leptospirosis (pathogen <em>Leptospira<\/em> species) spread among animals in wildlife and livestock reservoir populations, and this limits our ability to understand risks to spillover hosts such as humans.<\/p>\n<p style=\"padding-left: 40px\">We are working to address this gap, by studying the factors that drive recurring, deadly leptospirosis outbreaks in California sea lions (<em>Zalophus californianus<\/em>) along the Pacific coast of the US. Every fall, the disease causes sea lions to strand and die, and some years there are dramatic outbreaks that cause major mortality in the sea lion population. In collaboration with a broad team of partners, including scientists and veterinarians at <a href=\"http:\/\/www.marinemammalcenter.org\/\" target=\"_blank\" rel=\"noopener\">The Marine Mammal Center<\/a> and the National Marine Fisheries Service, we have assembled an extensive data set describing disease spread in this system for the past three decades. We are studying the disease in field, lab and clinical settings, and working with top microbiologists and genome scientists to conduct molecular analyses of the pathogen. Our findings are shedding new light on how the disease circulates among sea lions, why it causes major outbreaks in some years, and how it has persisted in the ecosystem for decades. We are also gaining new insights into the epidemiology of leptospirosis in animal populations. We are also using the data set to address classical questions in population ecology, such as the balance of intrinsic and extrinsic drivers in generating observed population dynamics.<\/p>\n<p style=\"padding-left: 40px\"><a name=\"zoonosis\"><\/a><\/p>\n<p style=\"padding-left: 40px\">We have expanded this project to study leptospirosis in some terrestrial mammals in the California coastal ecosystem, including the threatened Channel Island fox (<em>Urocyon littoralis<\/em>) and southern sea otter (<em>Enhydra lutris nereis<\/em>). This work, which is a collaboration with crucial partners including the National Park Service and California Department of Fish &amp; Wildlife, is exploring the community ecology of disease spread in this system, and how transmission between the marine and terrestrial realms may enable the pathogen to persist long-term in the coastal ecosystem.<\/p>\n<\/div><\/section><\/div><div  class='flex_column av-5os7c-ba81b0639129bb72c17eb2f260bec72c av_one_fourth  avia-builder-el-7  el_after_av_three_fourth  el_before_av_heading  flex_column_div  '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3ddo6h-03f29df1ef6cd900e3b8182c7eb13c7d\">\n.avia-image-container.av-lo3ddo6h-03f29df1ef6cd900e3b8182c7eb13c7d img.avia_image{\nbox-shadow:none;\n}\n.avia-image-container.av-lo3ddo6h-03f29df1ef6cd900e3b8182c7eb13c7d .av-image-caption-overlay-center{\ncolor:#ffffff;\n}\n<\/style>\n<div  class='avia-image-container av-lo3ddo6h-03f29df1ef6cd900e3b8182c7eb13c7d av-styling- avia-align-center  avia-builder-el-8  avia-builder-el-no-sibling '   itemprop=\"image\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\" ><div class=\"avia-image-container-inner\"><div class=\"avia-image-overlay-wrap\"><img decoding=\"async\" fetchpriority=\"high\" class='wp-image-82 avia-img-lazy-loading-not-82 avia_image ' src=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/sealion.jpg\" alt='' title='sealion'  height=\"720\" width=\"883\"  itemprop=\"thumbnailUrl\" srcset=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/sealion.jpg 883w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/sealion-300x245.jpg 300w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/sealion-768x626.jpg 768w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/sealion-705x575.jpg 705w\" sizes=\"(max-width: 883px) 100vw, 883px\" \/><\/div><\/div><\/div><\/div><\/p>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3enqck-f9a2e7389bcf3838a59f0d35b8e9b852\">\n#top .av-special-heading.av-lo3enqck-f9a2e7389bcf3838a59f0d35b8e9b852{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lo3enqck-f9a2e7389bcf3838a59f0d35b8e9b852 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lo3enqck-f9a2e7389bcf3838a59f0d35b8e9b852 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lo3enqck-f9a2e7389bcf3838a59f0d35b8e9b852 av-special-heading-h4  avia-builder-el-9  el_after_av_one_fourth  el_before_av_three_fourth '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >Cross-scale models of zoonotic viruses (including SARS-CoV-2)<\/h4><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n<div  class='flex_column av-4u19c-c3fc47e86387d3d256e0c89c145fccdf av_three_fourth  avia-builder-el-10  el_after_av_heading  el_before_av_one_fourth  first flex_column_div  '     ><section  class='av_textblock_section av-lo3dgei2-3f2da68929309960cb5b7c9aa1cdce80 '   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock'  itemprop=\"text\" ><p style=\"padding-left: 40px\">In the context of the COVID-19 pandemic, we draw upon our existing research on novel bat viruses and human respiratory pathogens to contribute to the ongoing effort to understand and combat the SARS-CoV-2 virus. With the <a href=\"https:\/\/batonehealth.org\/\" target=\"_blank\" rel=\"noopener noreferrer\">BatOneHealth<\/a> team, we have been conducting research on henipaviruses (e.g. Nipah, Hendra) at the bat-human interface. We draw upon this prior work and the network of collaborators we had developed through it to address SARS-CoV-2, a bat coronavirus. We develop a variety of projects that use theoretical and mathematical models to extract better information from experimental and epidemiological data, linking within-host processes to population scale dynamics.<\/p>\n<ul>\n<li style=\"list-style-type: none\">\n<ul>\n<li style=\"list-style-type: none\">\n<ul>\n<li>In collaboration with colleagues at the NIH Rocky Mountain Laboratories (RML) (<a href=\"https:\/\/www.niaid.nih.gov\/research\/vincent-j-munster-phd\" target=\"_blank\" rel=\"noopener noreferrer\">Munster Lab<\/a>), we study the <a href=\"https:\/\/doi.org\/10.1056\/NEJMc2004973\" target=\"_blank\" rel=\"noopener noreferrer\">persistence of the virus<\/a> in aerosols and on surfaces, developed <a href=\"https:\/\/doi.org\/10.7554\/eLife.65902\" target=\"_blank\" rel=\"noopener noreferrer\">mechanistic models<\/a> of virus persistence as a function of temperature and humidity, and use this knowledge to guide pandemic response.<\/li>\n<li>We develop kinetic models of individual SARS-CoV-2 infections, which we used to study dose-dependent disease progression in animal model data generated by collaborators at NIH RML (<a href=\"https:\/\/www.niaid.nih.gov\/research\/vincent-j-munster-phd\" target=\"_blank\" rel=\"noopener noreferrer\">Munster Lab<\/a>) and Cornell University (<a href=\"https:\/\/sites.google.com\/view\/aguilarlab\/home\" target=\"_blank\" rel=\"noopener noreferrer\">Aguilar Lab<\/a>).<\/li>\n<li>Using quantitative models of the immune response, we develop tools and best practice guidance for using <a href=\"https:\/\/doi.org\/10.7554\/eLife.60122\" target=\"_blank\" rel=\"noopener noreferrer\">serological data<\/a> to characterize SARS-CoV-2 epidemiology.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p style=\"padding-left: 40px\"><a name=\"influenza\"><\/a> Other ongoing projects include developing spatially-explicit mathematical models of individual coronavirus infections, with the aim of understanding how the virus spreads throughout the body and causes differential pathology across tissues.<\/p>\n<\/div><\/section><\/div>\n<div  class='flex_column av-4pidg-c67fcebe47ebcc7ca3a2149d9961aafe av_one_fourth  avia-builder-el-12  el_after_av_three_fourth  el_before_av_heading  flex_column_div  '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3dgswd-57c564c46200d463de54832ae4ef506f\">\n.avia-image-container.av-lo3dgswd-57c564c46200d463de54832ae4ef506f img.avia_image{\nbox-shadow:none;\n}\n.avia-image-container.av-lo3dgswd-57c564c46200d463de54832ae4ef506f .av-image-caption-overlay-center{\ncolor:#ffffff;\n}\n<\/style>\n<div  class='avia-image-container av-lo3dgswd-57c564c46200d463de54832ae4ef506f av-styling- avia-align-center  avia-builder-el-13  avia-builder-el-no-sibling '   itemprop=\"image\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\" ><div class=\"avia-image-container-inner\"><div class=\"avia-image-overlay-wrap\"><img decoding=\"async\" fetchpriority=\"high\" class='wp-image-81 avia-img-lazy-loading-not-81 avia_image ' src=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission.png\" alt='' title='CoV_transmission'  height=\"1539\" width=\"2406\"  itemprop=\"thumbnailUrl\" srcset=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission.png 2406w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-300x192.png 300w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-1030x659.png 1030w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-768x491.png 768w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-1536x983.png 1536w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-2048x1310.png 2048w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-1500x959.png 1500w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/CoV_transmission-705x451.png 705w\" sizes=\"(max-width: 2406px) 100vw, 2406px\" \/><\/div><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3eob76-641b5f5605cb762096da0df969c75295\">\n#top .av-special-heading.av-lo3eob76-641b5f5605cb762096da0df969c75295{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lo3eob76-641b5f5605cb762096da0df969c75295 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lo3eob76-641b5f5605cb762096da0df969c75295 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lo3eob76-641b5f5605cb762096da0df969c75295 av-special-heading-h4  avia-builder-el-14  el_after_av_one_fourth  el_before_av_three_fourth '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >Childhood hemagglutinin imprinting to influenza A viruses<\/h4><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n<div  class='flex_column av-44tuo-ee009165ae896e8c913c1112da56e488 av_three_fourth  avia-builder-el-15  el_after_av_heading  el_before_av_one_fourth  first flex_column_div  '     ><section  class='av_textblock_section av-lo3dhbv9-675ca70a5b13714f9439ef45e763e730 '   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock'  itemprop=\"text\" ><p style=\"padding-left: 40px\">Influenza pandemics occur every few decades, and persistently threaten to cause massive numbers of infections and fatalities, and halt the global economy. Pandemics occur when unfamiliar influenza viruses jump from animals into humans, and then manage to spread around the globe. Our lab is currently undertaking work to help forecast which age groups would be at the highest risk of severe infections in future pandemics, and which zoonotic influenza viruses would face the most resistance from pre-existing immunity if they were ever to jump from animals into humans.<\/p>\n<p style=\"padding-left: 40px\">Until recently, a key idea in influenza epidemiology was that the entire human population would lack immunity against an animal-origin pandemic virus. However, our <a href=\"http:\/\/science.sciencemag.org\/content\/354\/6313\/722\" target=\"_blank\" rel=\"noopener\">study<\/a> with collaborator <a href=\"http:\/\/eeb.arizona.edu\/people\/dr-michael-worobey-department-head\" target=\"_blank\" rel=\"noopener\"> Michael Worobey <\/a> showed for the first time that the human population actually has strong, pre-existing immunity against novel, zoonotic influenza A viruses with pandemic potential, and that this protection is predictably distributed across birth years. We analyzed data on all known cases of H5N1 and H7N9, two avian influenza viruses of great concern for pandemic emergence in humans, and showed that individuals gain lifelong, partial protection against novel hemagglutinin (HA) subtypes in the same genetic group as the influenza virus that caused their first infection during childhood (see diagram). We call this phenomenon, <strong>childhood HA imprinting<\/strong>.<\/p>\n<p style=\"padding-left: 40px\">As a birth year, 1968 marks a crucial turning point in HA imprinting protection. Anyone born before 1968 would have imprinted to HA group 1 (H1 or H2), whereas those born after 1968 have a much higher probability of imprinting to HA group 2 (H3, see figure at left). HA imprinting patterns explain why the majority of H5N1 cases observed to date have affected children and younger adults, while H7N9 has disproportionately affected older adults.<\/p>\n<p style=\"padding-left: 40px\"><a name=\"monkeypox\"><\/a><\/p>\n<p style=\"padding-left: 40px\">We can use routinely collected influenza surveillance data and demographic information to estimate the probability that an individual born in a particular year was first exposed to an influenza virus in group 1 or group 2. With this information, we are building models to forecast age distributions of infection in future pandemics, and to forecast whether potential pandemic viruses from group 1 or group 2 would face more resistance from pre-existing human immunity. We are also working with empirical collaborators to identify the specific immune mechanism responsible for HA imprinting protection. Additionally, we are working to understand whether vaccination in children has a negative or positive effect on HA imprinting protection, and to understand the impact of HA imprinting on the epidemiology of seasonal influenza viruses H1N1 and H3N2.<\/p>\n<\/div><\/section><\/div><div  class='flex_column av-3d564-688865e58f478d4fe108225b77a7dc76 av_one_fourth  avia-builder-el-17  el_after_av_three_fourth  el_before_av_heading  flex_column_div  '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3dhtc3-b656078bc62f4002cf7c8a53f8e44f28\">\n.avia-image-container.av-lo3dhtc3-b656078bc62f4002cf7c8a53f8e44f28 img.avia_image{\nbox-shadow:none;\n}\n.avia-image-container.av-lo3dhtc3-b656078bc62f4002cf7c8a53f8e44f28 .av-image-caption-overlay-center{\ncolor:#ffffff;\n}\n<\/style>\n<div  class='avia-image-container av-lo3dhtc3-b656078bc62f4002cf7c8a53f8e44f28 av-styling- avia-align-center  avia-builder-el-18  avia-builder-el-no-sibling '   itemprop=\"image\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\" ><div class=\"avia-image-container-inner\"><div class=\"avia-image-overlay-wrap\"><img decoding=\"async\" fetchpriority=\"high\" class='wp-image-80 avia-img-lazy-loading-not-80 avia_image ' src=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/flu.png\" alt='' title='flu'  height=\"1262\" width=\"1122\"  itemprop=\"thumbnailUrl\" srcset=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/flu.png 1122w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/flu-267x300.png 267w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/flu-916x1030.png 916w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/flu-768x864.png 768w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/flu-627x705.png 627w\" sizes=\"(max-width: 1122px) 100vw, 1122px\" \/><\/div><\/div><\/div><\/div><\/p>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3eouez-6e231db81181b8a387f1c57a4d00dd07\">\n#top .av-special-heading.av-lo3eouez-6e231db81181b8a387f1c57a4d00dd07{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lo3eouez-6e231db81181b8a387f1c57a4d00dd07 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lo3eouez-6e231db81181b8a387f1c57a4d00dd07 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lo3eouez-6e231db81181b8a387f1c57a4d00dd07 av-special-heading-h4  avia-builder-el-19  el_after_av_one_fourth  el_before_av_three_fourth '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >Mpox emergence in the Democratic Republic of Congo<\/h4><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n<div  class='flex_column av-2uek0-e541fe7cc719eab2d85bc31f1ce38390 av_three_fourth  avia-builder-el-20  el_after_av_heading  el_before_av_one_fourth  first flex_column_div  '     ><section  class='av_textblock_section av-lo3dieip-1fddb8c7bc43ef0dfda6490629baa853 '   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock'  itemprop=\"text\" ><p style=\"padding-left: 40px\">The greatest known threat of new human pathogens comes from &#8216;stuttering&#8217; zoonoses. These are pathogens that exhibit limited transmission among humans\u2014enough to cause a cluster of cases, but not enough to trigger an epidemic. Such stuttering chains of transmission are red flags for emergence risk, since the barrier of human-to-human transmission has been breached, but they have proven very difficult to study due to their rare and transient nature. Methods to analyze epidemiological data from these pathogens are sorely lacking (see figure from Science paper, above).<\/p>\n<p style=\"padding-left: 40px\">With <a href=\"http:\/\/www.ph.ucla.edu\/epi\/faculty\/rimoin\/rimoin.html\" target=\"_blank\" rel=\"noopener\">Anne Rimoin<\/a> in the UCLA School of Public Health and a team of collaborators, we are studying the dynamics of mpox at the wildlife-human interface in the Democratic Republic of the Congo. Mpox is a perfect case study for viral emergence: it transmits inefficiently among humans, but its transmission is rising as population immunity against poxviruses drops with time since the eradication of smallpox. We have extensive data on mpox epidemiology in the Congo basin from a historic surveillance program in the 1980s, and from on-going surveillance led by the UCLA team. This presents a unique opportunity to develop and test new models against two data sets that differ systematically in the degree of transmission<\/p>\n<p style=\"padding-left: 40px\">Our group is developing new modeling approaches to understand the rise of mpox in the Congo basin, and building tools to analyze data from any stuttering zoonosis. These include methods for assessing whether cases were infected by animal or human sources, and methods to estimate transmission parameters from the size distribution of human outbreaks. We are integrating these tools with disease transmission models to study the drivers of temporal and spatial patterns in mpox incidence, and to answer crucial questions such as how efficiently the virus spreads between humans. We\u2019re using ideas from community ecology to study how smallpox eradication has altered mpox epidemiology, to find general lessons for current and future disease eradication campaigns. In addition, the tools we\u2019re building will be applicable to other zoonotic threats such as H5N1 avian influenza or to re-emerging infections such as measles or pertussis in populations with low vaccine uptake.<\/p>\n<p style=\"padding-left: 40px\"><a name=\"evolution\"><\/a><\/p>\n<\/div><\/section><\/div>\n<div  class='flex_column av-1xjrg-c646119d170d3dc3795dc513d3367c92 av_one_fourth  avia-builder-el-22  el_after_av_three_fourth  el_before_av_heading  flex_column_div  '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3dint4-807fdd95498e5b760fbd6c0c946154a9\">\n.avia-image-container.av-lo3dint4-807fdd95498e5b760fbd6c0c946154a9 img.avia_image{\nbox-shadow:none;\n}\n.avia-image-container.av-lo3dint4-807fdd95498e5b760fbd6c0c946154a9 .av-image-caption-overlay-center{\ncolor:#ffffff;\n}\n<\/style>\n<div  class='avia-image-container av-lo3dint4-807fdd95498e5b760fbd6c0c946154a9 av-styling- avia-align-center  avia-builder-el-23  avia-builder-el-no-sibling '   itemprop=\"image\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\" ><div class=\"avia-image-container-inner\"><div class=\"avia-image-overlay-wrap\"><img decoding=\"async\" fetchpriority=\"high\" class='wp-image-79 avia-img-lazy-loading-not-79 avia_image ' src=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/monkeypox1.jpg\" alt='' title='monkeypox1'  height=\"768\" width=\"858\"  itemprop=\"thumbnailUrl\" srcset=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/monkeypox1.jpg 858w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/monkeypox1-300x269.jpg 300w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/monkeypox1-768x687.jpg 768w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/monkeypox1-705x631.jpg 705w\" sizes=\"(max-width: 858px) 100vw, 858px\" \/><\/div><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3eqkut-febe746529a1931a29b52281614b3638\">\n#top .av-special-heading.av-lo3eqkut-febe746529a1931a29b52281614b3638{\npadding-bottom:10px;\n}\nbody .av-special-heading.av-lo3eqkut-febe746529a1931a29b52281614b3638 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lo3eqkut-febe746529a1931a29b52281614b3638 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lo3eqkut-febe746529a1931a29b52281614b3638 av-special-heading-h4  avia-builder-el-24  el_after_av_one_fourth  el_before_av_three_fourth '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >Cross-scale models for evolutionary emergence of novel pathogens<\/h4><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n<div  class='flex_column av-1f33o-afe9621ea886c3f3de8baaac59e4745d av_three_fourth  avia-builder-el-25  el_after_av_heading  el_before_av_one_fourth  first flex_column_div  '     ><section  class='av_textblock_section av-lo3dj3vw-dcc4110917d09483b21660115c61a733 '   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock'  itemprop=\"text\" ><p style=\"padding-left: 40px\">Adaptive evolution can play a powerful role in pathogen emergence across species boundaries. A fast-growing empirical literature, propelled by sequencing technology, reverse genetics, and experimental infection studies, is mapping the impact of mutations on viral fitness across host species. But there is no framework to synthesize these findings in light of the key biological mechanisms at play, from viral growth within host individuals to the epidemiological processes of spillover, stuttering chains, and emergence.<\/p>\n<p style=\"padding-left: 40px\">In a collaboration with <a href=\"http:\/\/www-eve.ucdavis.edu\/sschreiber\/\" target=\"_blank\" rel=\"noopener\">Sebastian Schreiber<\/a> at UC Davis we worked to construct a multi-scale theory for pathogen emergence, combining concepts from virology, population genetics, and epidemic modeling (see schematic figure). We are building from the smallest scales up, studying how basic processes of viral replication and within-host pathogen dynamics can influence processes at larger scales. We have studied how evolutionary emergence processes within hosts are impacted by mechanisms of viral genome replication, and how the cost of deleterious mutations balances with the benefit of adaptive evolution to influence emergence probability. We are constructing a series of cross-scale models that link within-host selection to evolutionary emergence that can occur in the course of a stuttering chain of transmission.<\/p>\n<p style=\"padding-left: 40px\">Ultimately, this research aims to connect laboratory results in molecular virology to sequence data collected in experimental infections and field surveillance, to guide rational assessment of the risk from possible zoonotic threats. With these goals in mind, we are continuing to develop our models to incorporate greater realism and make connections to current empirical research. In collaboration with Ren Sun in the UCLA medical school, we applied our models to analyze data from high-throughput experiments characterizing fitness and drug resistance phenotypes of viruses such as hepatitis C virus.<\/p>\n<\/div><\/section><\/div><div  class='flex_column av-vdrk-dfc5adacb1eee1c2763a6dfb00d6eb79 av_one_fourth  avia-builder-el-27  el_after_av_three_fourth  avia-builder-el-last  flex_column_div  '     ><style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lo3djdm6-2cc5fd3d6446faceb7652cda7b0029de\">\n.avia-image-container.av-lo3djdm6-2cc5fd3d6446faceb7652cda7b0029de img.avia_image{\nbox-shadow:none;\n}\n.avia-image-container.av-lo3djdm6-2cc5fd3d6446faceb7652cda7b0029de .av-image-caption-overlay-center{\ncolor:#ffffff;\n}\n<\/style>\n<div  class='avia-image-container av-lo3djdm6-2cc5fd3d6446faceb7652cda7b0029de av-styling- avia-align-center  avia-builder-el-28  avia-builder-el-no-sibling '   itemprop=\"image\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\" ><div class=\"avia-image-container-inner\"><div class=\"avia-image-overlay-wrap\"><img decoding=\"async\" fetchpriority=\"high\" class='wp-image-78 avia-img-lazy-loading-not-78 avia_image ' src=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/virus_spread.png\" alt='' title='virus_spread'  height=\"221\" width=\"360\"  itemprop=\"thumbnailUrl\" srcset=\"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/virus_spread.png 360w, https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-content\/uploads\/sites\/318\/2023\/10\/virus_spread-300x184.png 300w\" sizes=\"(max-width: 360px) 100vw, 360px\" \/><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":4,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-76","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/pages\/76","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/comments?post=76"}],"version-history":[{"count":23,"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/pages\/76\/revisions"}],"predecessor-version":[{"id":459,"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/pages\/76\/revisions\/459"}],"wp:attachment":[{"href":"https:\/\/sites.lifesci.ucla.edu\/eeb-lloydsmith\/wp-json\/wp\/v2\/media?parent=76"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}