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<p class="MsoNormal"><span style="font-size:13.5pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none"><img width="600" height="171" style="width:6.25in;height:1.7812in" id="_x0000_i1037" src="cid:image001.png@01DBA47F.4D3BFB20" alt="Dissertation Defense Announcement at the Cullen College of Engineering"><o:p></o:p></span></p>
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<b><span style="font-size:18.0pt;color:#C8102E;mso-ligatures:none">Understanding Cytotoxic Mechanisms
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<b><span style="font-size:18.0pt;color:#C8102E;mso-ligatures:none">of Cancer Immunotherapies<o:p></o:p></span></b></p>
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<b><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Melisa J. Montalvo<o:p></o:p></span></b></p>
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<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">April 11, 2025; 9 a.m. to 10:30 a.m.</span><span style="font-family:"Arial",sans-serif;mso-ligatures:none"><o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Location: AERB 222 or
<a href="https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/85258985300__;!!LkSTlj0I!H0_MIUDnocH1ra9dWxidN4rkvhrxA-n5rJ-Ue_dBug6E8URx5B79NVDBTLfKjg_KuDPUBCYUajf7FtN-HFujlSCqCkE$">Zoom</a> <o:p></o:p></span></p>
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<b><span style="font-size:12.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Committee Chair:</span></b><span style="font-size:10.5pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none"><br>
</span><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Navin Varadarajan, Ph.D.<o:p></o:p></span></p>
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Mehmet Orman, Ph.D. | Richard Willson, Ph.D. | Meghana Trivedi, Pharm.D., Ph.D. |
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<span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Nabil Ahmed, Ph.D.</span><span style="font-size:10.5pt;font-family:"Arial",sans-serif;mso-ligatures:none"><o:p></o:p></span></p>
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<b><span style="font-family:"Arial",sans-serif;color:#C8102E;mso-ligatures:none">Abstract</span></b><span style="font-family:"Arial",sans-serif;color:#C8102E;mso-ligatures:none"><o:p></o:p></span></p>
<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Immunotherapies have revolutionized our ability to treat cancers effectively; therapeutics like antibody-based therapies
have yielded clinical success. Cancer immunotherapies rely on a patients’ immune cells to elicit anti-tumor responses; however not all patients respond to these therapeutics. To decode these discrepancies in response and understand the molecular mechanisms
associated with these therapeutics, a deep understanding of immune cell cytotoxicity is required to fully understand how to augment their anti-tumor efficacy.<o:p></o:p></span></p>
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<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Here, we explore the molecular mechanisms of antibody-dependent cellular cytotoxicity (ADCC) in natural killer (NK)
cells. Using integrated TIMING and single cell RNA sequencing, we identified a population of killer NK cells that perform ADCC efficiently and correlate with clinical responses to trastuzumab. From functional validation of the killer signature, we discovered
that 1) inhibiting CD16 shedding does not improve ADCC and 2) killers upregulate interferons which can be stimulated with the STING agonist, 2’3’-cGAMP, to accelerate tumor killing through increased ADCC-mediated degranulation. We demonstrate that knockouts
of the degranulating marker, NKG7, abolished lytic granule exocytotsis, highlighting the essential role of NKG7 in ADCC.
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<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Collectively, our findings uncovered unique cytotoxic features associated with anti-tumor efficacy by immune therapies,
advancing strategies to improve cancer therapeutics.</span><span style="font-size:10.5pt;line-height:160%;font-family:"Arial",sans-serif;mso-ligatures:none"><o:p></o:p></span></p>
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<b><span style="font-size:12.0pt;font-family:"Arial",sans-serif;color:#C8102E;mso-ligatures:none"><img border="0" width="600" height="82" style="width:6.25in;height:.8541in" id="_x0000_i1042" src="cid:image002.png@01DBA47F.4D3BFB20" alt="Engineered For What's Next"><o:p></o:p></span></b></p>
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