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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@01DBA7D0.26F8D740" 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">Molecular Mechanisms of Pathological Crystallization and the Effects of Crystal Growth Modifiers in Biomimetic Systems<o:p></o:p></span></b></p>
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<b><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Dipayan Chakraborty<o:p></o:p></span></b></p>
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<span style="font-size:13.5pt;mso-ligatures:none"><o:p> </o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><span style="font-size:11.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">April 14, 2025; 3 p.m. to 5 p.m.
</span><span style="font-size:11.0pt;line-height:150%;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-size:11.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Location: AERB, Room #100<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><b><span style="font-size:11.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Virtual:
<a href="https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/83857358511?pwd=FWHeEUGpaiV7LROalgBiokADEnSNRl.1__;!!LkSTlj0I!G7wO1uSSI8tP8dgJTDEvNAyMZRYT1FHSSYFaSm_YpGyEXCvWF68wucgwTKMnVU4W-mcHRrMSktEdBLWOlS9MrluZYzs$" target="_blank" title="https://uh-edu-cougarnet.zoom.us/j/83857358511?pwd=FWHeEUGpaiV7LROalgBiokADEnSNRl.1">
<span style="color:#0563C1">Zoom link</span></a> (Meeting ID: </span></b><span style="font-size:11.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">838 5735 8511<b> Passcode:
</b>652777<b>)<o:p></o:p></b></span></p>
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<b><span style="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-size:11.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Jeffrey D. Rimer, Ph.D.<o:p></o:p></span></p>
<p class="MsoNormal" align="center" style="text-align:center;line-height:150%"><b><span style="font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Committee Members:</span></b><span style="font-size:11.0pt;line-height:150%;font-family:"Arial",sans-serif;color:black;mso-ligatures:none"><br>
Peter G. Vekilov, Ph.D. | Gul H. Zerze, Ph.D. | T. Randall Lee, Ph.D. | <o:p></o:p></span></p>
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<span style="font-size:11.0pt;font-family:"Arial",sans-serif;color:black;mso-ligatures:none">Naim Maalouf, 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:"Times New Roman",serif;color:black;mso-ligatures:none">Pathological crystallization is prevalent in various human diseases that include kidney stones (calcium oxalate
or calcium phosphate crystals), gout (monosodium urate crystals in joints), gallstones (cholesterol or bilirubin crystals), and atherosclerosis (cholesterol crystals in plaques), among others. These processes typically involve mechanisms leading to local supersaturation
of solutes, nucleation of one or more different crystal structures (e.g., polymorphs), crystal growth, and aggregation. Treatment of these diseases involves serval approaches that include (but are not limited to) methods of reducing solute concentration, lifestyle
changes to prevent recurrence, and the use of crystallization inhibitors (e.g., allopurinol for gout). This presentation will focus on two types of pathological crystals: cholesterol and calcium minerals.
<o:p></o:p></span></p>
<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Times New Roman",serif;color:black;mso-ligatures:none"><o:p> </o:p></span></p>
<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Times New Roman",serif;color:black;mso-ligatures:none">Cholesterol is prominently involved in the development of atherosclerotic plaques in the arteries, and the formation
of gallstones from bile. Despite these global healthcare challenges, there is a paucity of research exploring the underlying mechanisms of cholesterol crystallization. Nevertheless, it is widely recognized that unraveling approaches to control the precipitation
of cholesterol hold immense potential in the development of novel pharmaceutical interventions for the treatment of these conditions. Prior studies have used lipids as biomimetic media to study bulk cholesterol crystallization; however, these systems are not
amenable to facile in situ characterization techniques. To this end, we selected a binary mixture of water and alcohol as a lipid surrogate to examine cholesterol crystallization. We used a combination of oblique illumination microscopy (OIM) and dynamic light
scattering (DLS) to prove that cholesterol nucleates nonclassically involving the assembly of clusters while
<i>in situ </i>atomic force microscopy (AFM) confirmed that the surface dynamics involves classical layered growth from defects (dislocations), a typical surface diffusion phenomenon. We posit surface diffusion limitation leads to cessation of growth which
leads to self-inhibition of the crystals. We also found the dissolution phenomena to be a combination of classical and nonclassical mechanisms. Although it dissolves by both layer-by-layer and etch pit formation, dissolution of the monomers leads to cluster
formation and reattachment on the surface and its growth in purely undersaturated media, making the surface difficult to fully dissolve. Overall, our study reveals a very complex and unique mechanism of cholesterol crystallization that contributes to a deeper
understanding of cholesterol-related pathological conditions and offers potential avenues for the development of targeted therapeutic interventions.
<o:p></o:p></span></p>
<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Times New Roman",serif;color:black;mso-ligatures:none"><o:p> </o:p></span></p>
<p class="MsoNormal" style="text-align:justify;line-height:160%"><span style="font-family:"Times New Roman",serif;color:black;mso-ligatures:none">Nephrolithiasis is heavily associated with calcium mineralization. Notably, the incidence rates of calcium phosphate
(CaP) stones have markedly risen over the last four decades. Although frequently encountered, there is currently no proven treatment to prevent recurrent CaP stone disease. CaP stone formers (SF) experience high rates of recurrence and need for repeat surgery,
reflecting the suboptimal prophylaxis by current medical regimens. The major metabolic abnormalities identified in CaP SF include high urine pH (UpH), low urine citrate (UCit), and hypercalciuria. Efficacy of treatments that reduce recurrence of calcium stones
(thiazides, citrate) was primarily shown in calcium oxalate SF, and carry drawbacks in CaP SF: lower UCit with thiazides, and alkalinuria with citrate counteracting their beneficial effects. There is a dire need for specific therapy for CaP SFs. To this end,
we have been researching novel growth modifiers to both prevent CaP formation and function as dissolving agents. Recent efforts have focused on comparing the effects of citrate (CA) and hydroxycitrate (HCA). The latter is more potent and is being tested as
a potential therapeutic to complement the microscopic and macroscopic <i>in vitro
</i>tests in our laboratory.<o:p></o:p></span></p>
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<b><span style="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@01DBA7D0.26F8D740" alt="Engineered For What's Next"><o:p></o:p></span></b></p>
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