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<span style="font-size:12.0pt; line-height:150%; font-family:"Times New Roman",serif"><img width="600" height="171" id="x_Picture_x0020_3" alt="Dissertation Defense Announcement at the Cullen College of Engineering" style="width:6.25in; height:1.7812in" data-outlook-trace="F:1|T:1" src="cid:image005.jpg@01D845D5.17B10F60"></span><span style="font-size:12.0pt; line-height:150%; font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:16.0pt; line-height:150%; font-family:"Times New Roman",serif; color:red; text-transform:uppercase">Functional metrics of efficacious CAR T cells revealed by multi-dimensional single-cell profiling</span></b></p>
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<span style="font-size:12.0pt; line-height:150%; font-family:"Times New Roman",serif; text-transform:uppercase"> </span></p>
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<b><span style="font-size:13.5pt; line-height:150%; font-family:"Times New Roman",serif">Ali Rezvan</span></b><span style="font-size:13.5pt; line-height:150%; font-family:"Times New Roman",serif"></span></p>
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<span style="font-family:"Times New Roman",serif">November 30, 2022; 12:00 PM – 2:00 PM (CST)</span></p>
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<span style="font-family:"Times New Roman",serif"><br>
<b>Zoom:</b> <a href="https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/98348502418?pwd=eXdCc3U1QnJTVVZJZE1FalVHNGo0dz09__;!!LkSTlj0I!AgMO3PjDmMI_JnMNdB2ODxqWfHgR0h-gec4cYY_dJns5lBQx8f8IJu14hz80FoO7jmApoK7Czk1gbsCmf6GK0wWdpf0$" data-auth="NotApplicable">
https://uh-edu-cougarnet.zoom.us/j/98348502418?pwd=eXdCc3U1QnJTVVZJZE1FalVHNGo0dz09</a></span></p>
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<b><span style="font-family:"Times New Roman",serif">Committee Chair:</span></b><span style="font-family:"Times New Roman",serif"><br>
Navin Varadarajan, PhD</span></p>
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<b><span style="font-family:"Times New Roman",serif">Committee Members:</span></b><span style="font-size:10.0pt; line-height:150%; font-family:"Times New Roman",serif"><br>
Richard Willson, Ph.D. <b>| </b>Jacinta Conrad, Ph.D. <b>|</b> Chandra Mohan, Ph.D.
<b>|</b> Harjeet Singh, PhD. |<span style="color:black"> </span></span></p>
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<span style="font-size:10.0pt; line-height:150%; font-family:"Times New Roman",serif; color:black">Shaun Xiaoliu Zhang, PhD.</span><span style="font-size:10.5pt; line-height:150%; font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:12.0pt; line-height:150%; font-family:"Times New Roman",serif; color:#C8102E">Abstract</span></b><span style="font-size:12.0pt; line-height:150%; font-family:"Times New Roman",serif; color:#C8102E"></span></p>
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<span style="font-family:"Times New Roman",serif; color:black">Chimeric antigen receptors (CAR) T cells for B-cell malignancies serve as a model for identifying T-cell subsets with superior clinical activity. We profiled the infusion products (IP) of patients
with large B-cell lymphoma (LBCL) using multi-omic single-cell assays to reveal the therapeutic potential of CD19-CAR+ T cells. Functional profiling using timelapse imaging microscopy in nanowell grids (TIMING) profiling revealed that T cells from responders
showed high migration and serial killing. Cellular profiling using confocal microscopy revealed that migration is correlated with both mitochondrial and lysosomal volume; and molecular profiling scRNA-seq demonstrated that T cells from responders were enriched
in pathways related to T-cell killing, migration and actin cytoskeleton, and in vivo persistence. T cells enriched for migratory capacity showed sustained serial killing and optimal in vivo efficacy. Our results demonstrate that migration is a cell-intrinsic
biomarker desired in the bioactivity of CAR+ T cells associated with clinical antitumor efficacy.</span></p>
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<span style="font-size:12.0pt; font-family:"Times New Roman",serif"><img border="0" width="600" height="82" id="x_Picture_x0020_4" alt="Engineered For What's Next" style="width:6.25in; height:.8541in" data-outlook-trace="F:1|T:1" src="cid:image006.jpg@01D845D5.17B10F60"></span><span style="font-size:12.0pt; font-family:"Times New Roman",serif"></span></p>
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