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<link rel="preload" fetchpriority="high" href="/badge.png" as="image" type="image/png" media="width >= 48rem"/> <link rel="preload" fetchpriority="high" href="/dna.png" as="image" type="image/png"/> <meta name="description" content="Zhao lab website"/><!----><!--1seozpa--><!----><title>Research | Zhao Lab</title> 15 <link href="../_app/immutable/assets/0.CCPZPkIX.css" rel="stylesheet"> 16 </head> 17 <body data-sveltekit-preload-data="hover"> 18 <div style="display: contents"><!--[--><!--[0--><!--[--><!--[--><!--$s1--><!----> <div class="flex min-h-screen flex-col"><header><div class="grid h-80 bg-[url('/dna.png')] bg-cover bg-fixed bg-top bg-no-repeat"><div class="mt-auto"><div class="grid grid-cols-[1fr_auto] bg-contain bg-right bg-no-repeat md:bg-[url('/badge.png')]"><h1 class="text-6xl font-thin">
18Zhao Lab</h1> <label for="s1-openMenu" class="aspect-square translate-y-1 md:hidden"><svg xmlns="http://www.w3.org/2000/svg" width="24" height="24" viewBox="0 0 24 24" fill="none" stroke="currentColor" stroke-width="1" stroke-linecap="round" stroke-linejoin="round" class="lucide-icon lucide lucide-menu size-full"><!--[--><!----><path d="M4 5h16"><!----></path><!----><!----><path d="M4 12h16"><!----></path><!----><!----><path d="M4 19h16"><!----></path><!----><!--]--><!----><!----></svg><!----> <span class="sr-only">Open menu</span></label></div> <input type="radio" id="s1-openMenu" name="s1-menuToggle" class="peer sr-only md:hidden"/> <input type="radio" id="s1-closeMenu" name="s1-menuToggle" class="sr-only md:hidden"/> <nav class="inset-0 z-10 w-full peer-checked:block max-md:fixed max-md:hidden max-md:h-screen max-md:bg-white md:shadow-inner md:backdrop-blur-xs"><ul class="grid-flow-col max-md:space-y-4 md:grid"><li><a class="[--my-sibling-index:0] inline-block text-6xl decoration-from-font max-md:my-animate-bounce max-md:font-thin max-md:underline md:size-full md:p-4 md:text-center md:text-base" href="../">Home</a></li> <li><a class="[--my-sibling-index:1] inline-block text-6xl decoration-from-font max-md:my-animate-bounce max-md:font-thin max-md:underline md:size-full md:p-4 md:text-center md:text-base" href="../positions/">Positions</a></li> <li><a class="[--my-sibling-index:2] inline-block text-6xl decoration-from-font max-md:my-animate-bounce max-md:font-thin max-md:underline md:size-full md:p-4 md:text-center md:text-base" href="../research/">Research</a></li> <li><a class="[--my-sibling-index:3] inline-block text-6xl decoration-from-font max-md:my-animate-bounce max-md:font-thin max-md:underline md:size-full md:p-4 md:text-center md:text-base" href="../people/">People</a></li> <li><a class="[--my-sibling-index:4] inline-block text-6xl decoration-from-font max-md:my-animate-bounce max-md:font-thin max-md:underline md:size-full md:p-4 md:text-center md:text-base" href="../publications/">Publications</a></li><!----></ul> <label for="s1-closeMenu" class="md:hidden"><svg xmlns="http://www.w3.org/2000/svg" width="48" height="48" viewBox="0 0 24 24" fill="none" stroke="currentColor" stroke-width="1" stroke-linecap="round" stroke-linejoin="round" class="lucide-icon lucide lucide-x inline"><!--[--><!----><path d="M18 6 6 18"><!----></path><!----><!----><path d="m6 6 12 12"><!----></path><!----><!--]--><!----><!----></svg><!----> <span class="sr-only">Close menu</span></label></nav></div></div></header> <main class="flex-1"><!--[0--><div class="m-auto max-w-399"><div class="columns-xs"><h1 class="mx-3 text-xl font-thin">Molecular Dissection of BRCA1 Tumor Suppression Networks</h1> <p class="mx-3 indent-8">BRCA1 heterodimerizes with another tumor suppressor BARD1, and the resulting complex possesses 19 DNA binding and ubiquiFtin E3 ligase activities, and interacts with proteins that function in 20 diverse biological processes, including homology-directed DNA repair (HDR), DNA replication 21 fork maintenance, DNA damage checkpoints, R-loop resolution and mitotic chromosome 22 segregation. However, the mechanisms that underlie BRCA1-BARD1 dependent processes have not 23 been determined because of the immense challenge of expressing and purifying the BRCA1-BARD1 24 complexes for mechanistic workup. Importantly, we have overcome this technical challenge, 25 which has allowed us to begin providing mechanistic information regarding the roles of 26 BRCA1-BARD1 in HDR (Zhao et. al. Nature 2017). In the future, we will continue to dissect the 27 tumor suppression mechanisms of BRCA1-BARD1, with one specific focus on its ubiqutin E3 ligase 28 activity, by using a synergistic approach of protein biochemistry, cell biology, and 29 structural biology.</p> <img src="/_app/immutable/assets/art-1.CC0eS71r.webp" alt=""/> <hr class="my-3"/> <h1 class="mx-3 text-xl font-thin">Mechanism of Homology Search and DNA Invasion</h1> <img src="/_app/immutable/assets/art-2.BJhqGZ8D.webp" alt=""/> <p class="mx-3 indent-8">We discovered that BRCA1-BARD1 functions in the step of homology search and DNA invasion 30 during homology-directed DNA repair (HDR). As BRCA1-BARD1 forms complexes with a number of 31 protein factors that also are involved in HDR, we will investigate whether and how those 32 BRCA1-BARD1 complexes particulate in the process (BRCA1 dependent pathway), and define its 33 relationship with the BRCA1 independent pathways.</p> <hr class="my-3"/> <h1 class="mx-3 text-xl font-thin">Probe Therapies for BRCA-related Cancers</h1> <p class="mx-3 indent-8">Pathogenic mutations in BRCA1 and BRCA2 lead to genome instability and predispose afflicted 34 individuals to diverse cancer types. BRCA1/2 mutant cancer patients in general respond well to 35 therapy involving the use of a PARP inhibitor (PARPi) or platinum salt, but most would acquire 36 drug resistance over time. Furthermore, many more mutations foun
36d in patients are variants of 37 unknown significance (VUSs), as we do not yet know whether the gene mutations in question 38 actually affect function and how severe the defect is. As such, it is essential to study the 39 mutants to probe effective therapies for patient with VUSs or resistance to standard 40 treatment.</p> <img src="/_app/immutable/assets/art-3.h481ScU2.webp" alt=""/></div><!----></div><!--]--></main> <footer class="bg-amber-600"><div class="m-auto grid max-w-399 grid-cols-[auto_auto_1fr] gap-4"><section><h1 class="font-semibold">Address</h1> <address><p>University of Texas at San Antonio</p> <p>7703 Floyd Curl Drive</p> <p>San Antonio, Texas 78229</p></address></section> <nav><ul><li><a class="[--my-sibling-index:0]" href="../">Home</a></li> <li><a class="[--my-sibling-index:1]" href="../positions/">Positions</a></li> <li><a class="[--my-sibling-index:2]" href="../research/">Research</a></li> <li><a class="[--my-sibling-index:3]" href="../people/">People</a></li> <li><a class="[--my-sibling-index:4]" href="../publications/">Publications</a></li><!----></ul></nav></div></footer></div><!--]--><!----><!--]--><!--]--> <!--[-1--><!--]--><!--]--> 41 42
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