<html>
<head>
<meta http-equiv="Content-Type" content="text/html; charset=Windows-1252">
<style type="text/css" style="display:none;"> P {margin-top:0;margin-bottom:0;} </style>
</head>
<body dir="ltr">
<div style="font-family: Calibri, Arial, Helvetica, sans-serif; font-size: 12pt; color: rgb(0, 0, 0); background-color: rgb(255, 255, 255);" class="elementToProof">
<br>
</div>
<div class="elementToProof">
<div style="font-family: Calibri, Arial, Helvetica, sans-serif; font-size: 12pt; color: rgb(0, 0, 0);">
<br>
</div>
<div id="Signature">
<div>
<div></div>
<div id="divtagdefaultwrapper" dir="ltr" style="font-size:12pt; color:#000000; font-family:Calibri,Helvetica,sans-serif">
<div style="font-family:Calibri,sans-serif; font-size:14px; line-height:normal"><b>Rachel Knudsen</b></div>
<div style="font-family:Calibri,sans-serif; font-size:14px; line-height:normal">
<div>Executive Director of Communications</div>
<div>Cullen College of Engineering</div>
<div>Engineering Building 2, Suite E311<br>
</div>
<div>University of Houston</div>
<div><span style="font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols; line-height:normal">Houston, TX 77204-4007</span><br>
</div>
<div>713.743.4379 – <a href="mailto:riward@central.uh.edu" style="color:purple">riward@central.uh.edu</a><br>
</div>
</div>
</div>
</div>
</div>
</div>
<div id="appendonsend"></div>
<hr style="display:inline-block;width:98%" tabindex="-1">
<div id="divRplyFwdMsg" dir="ltr"><font face="Calibri, sans-serif" style="font-size:11pt" color="#000000"><b>From:</b> Thomas, Yolanda M <YMThomas@Central.UH.EDU><br>
<b>Sent:</b> Tuesday, November 29, 2022 9:53 AM<br>
<b>To:</b> Knudsen, Rachel W <riward@Central.UH.EDU><br>
<b>Subject:</b> Cullen College Dissertation Defense Announcement - Arash Saeedi</font>
<div> </div>
</div>
<style>
<!--
@font-face
{font-family:"Cambria Math"}
@font-face
{font-family:Calibri}
p.x_MsoNormal, li.x_MsoNormal, div.x_MsoNormal
{margin:0in;
margin-bottom:.0001pt;
font-size:11.0pt;
font-family:"Calibri",sans-serif}
a:link, span.x_MsoHyperlink
{color:#0563C1;
text-decoration:underline}
a:visited, span.x_MsoHyperlinkFollowed
{color:#954F72;
text-decoration:underline}
p.x_msonormal0, li.x_msonormal0, div.x_msonormal0
{margin-right:0in;
margin-left:0in;
font-size:12.0pt;
font-family:"Times New Roman",serif}
p.x_Default, li.x_Default, div.x_Default
{margin:0in;
margin-bottom:.0001pt;
text-autospace:none;
font-size:12.0pt;
font-family:"Times New Roman",serif;
color:black}
span.x_EmailStyle19
{font-family:"Calibri",sans-serif;
color:#222A35;
font-weight:normal;
font-style:normal}
.x_MsoChpDefault
{font-size:10.0pt}
@page WordSection1
{margin:1.0in 1.0in 1.0in 1.0in}
div.x_WordSection1
{}
-->
</style>
<div lang="EN-US" link="#0563C1" vlink="#954F72">
<div class="x_WordSection1">
<div align="center">
<table class="x_MsoNormalTable" border="0" cellspacing="0" cellpadding="0" width="600" style="width:6.25in">
<tbody>
<tr>
<td style="padding:0in 0in 0in 0in">
<p class="x_MsoNormal" style="line-height:150%"><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>
<div align="center">
<table class="x_MsoNormalTable" border="0" cellspacing="0" cellpadding="0" style="background:white">
<tbody>
<tr>
<td width="642" style="width:481.5pt; padding:30.0pt 15.0pt 7.5pt 15.0pt">
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<b><span style="font-size:16.0pt; line-height:150%; font-family:"Times New Roman",serif; color:red; text-transform:uppercase">Engineering Non-cytotoxic Delivery of Proteins by T cells via Fusion to NPC2
</span></b></p>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<span style="font-size:12.0pt; line-height:150%; font-family:"Times New Roman",serif; text-transform:uppercase"> </span></p>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<b><span style="font-size:13.5pt; line-height:150%; font-family:"Times New Roman",serif">Arash Saeedi</span></b><span style="font-size:13.5pt; line-height:150%; font-family:"Times New Roman",serif"></span></p>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<span style="font-family:"Times New Roman",serif">December 5, 2022; 1:00 PM – 3:00 PM (CST)</span></p>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<span style="font-family:"Times New Roman",serif"><br>
<b>Zoom Link:</b> <a href="https://urldefense.com/v3/__https:/uh-edu-cougarnet.zoom.us/j/94533319289?pwd=WG5SWERERjhuR3hLSTRUOUxCYjZyZz09__;!!LkSTlj0I!FscYlfSmUu9eq4kmTgrHaAQngpD3XqtQ-vBOqUqFxQy7-ZmOf5Ux0voJjqxRViDmV7qADn1Ee94oeou12HFTi-L2XA$" target="_blank">
https://uh-edu-cougarnet.zoom.us/j/94533319289?pwd=WG5SWERERjhuR3hLSTRUOUxCYjZyZz09</a></span></p>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<span style="font-family:"Times New Roman",serif">Meeting ID: 945 3331 9289<br>
Passcode: 732852</span></p>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<span style="font-family:"Times New Roman",serif"> </span></p>
<p class="x_MsoNormal" align="center" style="margin-bottom:3.75pt; text-align:center; line-height:150%">
<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>
<p class="x_MsoNormal" align="center" style="text-align:center; line-height:150%">
<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>Mehmet Orman, Ph.D. <b>|</b> Weiyi Peng, Ph.D. <b>
|</b> Fatima Merchant, PhD. <span style="color:black"></span></span></p>
</td>
</tr>
<tr style="height:405.9pt">
<td width="642" style="width:481.5pt; padding:0in 15.0pt 15.0pt 15.0pt; height:405.9pt">
<p class="x_MsoNormal" style="line-height:150%"><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>
<p class="x_MsoNormal" style="text-align:justify; line-height:150%"><span style="font-family:"Times New Roman",serif; color:black"> Engineering cellular therapeutics by programming T cells has great potential in immunology. The primary mechanism employed
by T cells for the specific transfer of proteins at the immunological synapse is via the lysosomal perforin pathway that facilitates the transfer of cytotoxic granzymes leading to apoptosis in target cells. Facilitating the delivery of non-cytotoxic proteins
through perforin oligomers will dramatically expand the range of protein cargos that T cells can traffic to the target cells. Here, we have identified the intralysosomal protein, NPC2, as a chaperone that can facilitate the delivery of T-cell derived reporter
proteins through perforin pores at the immunological synapse. Structural and biophysical considerations suggested that NPC2 could traverse through perforin pores and in vitro experiments confirmed the transport of purified NPC2 through perforin pores on cell
membranes. To characterize the ability of NPC2 to facilitate the transfer of payloads in T cells, we constructed NPC2-mCherry fusion proteins in T cells. Using confocal microscopy and flow cytometry, we confirmed the colocalization of the NPC2 fused protein
with lytic granules and the transfer of the fluorescent protein payload from T cells to target cells in co-culture experiments. The NPC2 fusion enabled the localization of mCherry to secretory lysosomes in mouse TCR CD8<sup>+</sup> T cells and human CD4<sup>+</sup>
and CD8<sup>+</sup> chimeric antigen receptor (CAR) T cells. Finally, we introduce a novel method for expression of NPC2 fused toxins within CAR T cells for treating immune resistant tumor cells. These results illustrate that by using NPC2 as a molecular
chaperone, the NPC2-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies.
</span></p>
</td>
</tr>
</tbody>
</table>
</div>
</td>
</tr>
<tr>
<td style="padding:0in 0in 0in 0in">
<p class="x_MsoNormal"><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>
</td>
</tr>
</tbody>
</table>
</div>
<p class="x_MsoNormal"> </p>
</div>
</div>
</body>
</html>