Digital Commons Network^™

Long-Term Dynamic Profiles Of Cognitive Kinases Induced By Different Learning Protocols, Yili Zhang, Rong-Yu Liu, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Learning is associated with activation of multiple protein kinases, but few details are known about the activation dynamics in response to different learning protocols. We addressed this issue by examining the long-term dynamics of kinases critical for long term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse. Three serotonin (5-HT) protocols have been found to induce LTF with distinct effectiveness: the five-pulse regular-spaced Standard protocol; the five-pulse irregular-spaced Enhanced protocol; and the two-pulse protocol with an interval of 45 min. We previously compared long-term dynamics of the mitogen-activated protein kinase (MAPK) isoform ERK after these protocols. Here we examined the …

A Novel D-Peptide Modulates Dclk1 Gelsolin Interactions, Reducing Pdac Tumor Growth, Landon L. Moore, Dongfeng Qu, Parthasarathy Chandrekesan, Kamille Pitts, Randal May, Byron E. Anderson, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

What drives inflammation-associated tumorigenesis and progression in pancreatic ductal adenocarcinoma (PDAC)? Doublecortin-like kinase 1 (DCLK1) is a central driver of inflammation-associated tumorigenesis, with elevated expression linked to worse clinical outcomes. Two isoforms of DCLK1 possess a unique extracellular domain (ECD). DCLK1 isoform 2 contains two microtubule-binding domains, while isoform 4, lacks the microtubule-binding domains but, plays a pivotal role in tumor progression. We identified novel D-peptides that selectively target this ECD, significantly suppressing PDAC cell proliferation in vitro and tumor growth in xenograft models without inducing cell death. In silico modeling and binding assays revealed DCLK1 isoform 4 interacts with …

Limitations Of The Radiotheranostic Concept In Neuroendocrine Tumors Due To Lineage-Dependent Somatostatin Receptor Expression On Hematopoietic Stem And Progenitor Cells, Nghia Nguyen, Yu Min, Jennifer Rivière, Mark Van Der Garde, Sukhen Ghosh, Laura M Bartos, Matthias Brendel, Florian Bassermann, Ali Azhdarinia, Wolfgang A Weber, Katharina S Götze, Susanne Kossatz

Faculty, Staff and Student Publications

Rationale: Radiopharmaceutical therapy (RPT) has become an effective treatment option for neuroendocrine tumors (NETs) and castration-resistant prostate cancer and is in clinical development for many indications. One of the major advantages of theranostic RPT is that the distribution of radiopharmaceuticals in the human body can be imaged, and radiation doses to the patient's organs can be calculated. However, accurate dosimetry may be fundamentally limited by microscopic heterogeneity of radiopharmaceutical distribution.

Methods: We developed fluorescent analogs of somatostatin-receptor-subtype 2 (SSTR2) targeting Lutetium-177 labeled radiopharmaceuticals that are clinically used in patients with NETs and studied their uptake by hematopoietic stem and progenitor …

Administration Of Anti-Gfap Antibodies Increases Cgrp Expression And Increases Pain Hypersensitivity In Spinal Cord Injured Animals, Georgene W Hergenroeder, Samuel T Molina, Juan J Herrera

Faculty, Staff and Student Publications

Background: Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.

Objective: Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined …

Safety Of Indocyanine Green Microdosing For Clinical Imaging Of Csf Ventricular Dynamics And Extracranial Outflow, Miriam Zamorano, Banghe Zhu, Ahmed T Massoud, Jonathan Hendricks, H Alex Choi, Pedram Peesh, Brandon A Miller, Xinhai Robert Zhang, Manish N Shah, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Background and purpose: Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct administration into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating the feasibility of using ICG microdosing into the CSF, we sought to evaluate its nonclinical safety profile and obtain surrogate measures in adults prior to its use in human neonates.

Methods: Evaluation of ICG toxicity was conducted in mixed primary CNS cell cultures and in an extended safety study of juvenile rat pups deploying intraventricular injections of saline (as control) or ICG. Analysis of …

Enl Mutation And Aml: A New Model That Reveals Oncogenic Condensate’S Function In Leukemogenesis, Zhong Fan, Yanan Jiang, Xiaotian Zhang

Faculty, Staff and Student Publications

Precise regulation of gene expression is essential for proper development and the maintenance of homeostasis in organisms. Studies have shown that some transcriptional regulatory proteins influence gene expression through the formation of dynamic, locally concentrated assemblies known as condensates, while dysregulation of transcriptional condensates was associated with several cancers, such as Ewing sarcoma and AML [Wang Y et al. (2023) Nat Chem Biol 19, 1223-1234; Chandra B et al. (2022) Cancer Discov 12, 1152-1169]. Mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL) have been shown to form discrete condensates at endogenous genomic targets, but it remains unclear how ENL mutations …

Pick Up A Frog, Or Pet A Dog; Animals Are Our First Teachers, Allison Ratner

Antioch University Dissertations & Theses

This dissertation’s goal was an attempt to answer the question: What are the emotional, cognitive, and/or spiritual effects of children’s relationships/interactions with animals that potentially impact their development? By utilizing autoethnography, I analyzed instances from my own life where interacting with animals changed me permanently; my thinking, my knowing, my feeling, my judgement, my empathy, my attitude, and my ethics. With a standpoint rooted in the research of experts from the fields of psychology and education, I combined my personal knowledge gained over a lifetime, to grant merit to the profundity of children’s relationships with animals. With the analyzed data, …

Folate Receptor Β Performs An Immune Checkpoint Function In Activated Macrophages, Fenghua Zhang, Md Yusuf Al-Amin, Sagar Utturkar, Rina Jiang, Gregory Cresswell, Rami Alfar, Ian Ophaug-Johansen, Gabriel Bachman, Madduri Srinivasarao, Richard Finnell, Amaya Puig-Kröger, Timothy Ratliff, Philip S Low

Faculty, Staff and Students Publications

Monocytes and macrophages are sentinels of the immune system that distinguish themselves from other cells by expressing the beta isoform of the folate receptor (FRβ). Because FRβ does not bind folate until the monocyte/macrophage is exposed to immunosuppressive cytokines, the question naturally arose whether FRβ might also perform an immune-related function. To examine this matter, we compared the properties of wild type (WT) and FRβ knockout mice. We observe that FRβ knockout (KO) mice display autoimmune symptoms that can include alopecia, enlarged spleens, and dermatitis, despite having normal cellular folate levels. We further demonstrate that syngeneic tumors (TRAMP C2, MC38) …

Distinct Gut Microbiome Features Characterize Fasciola Hepatica Infection And Predict Triclabendazole Treatment Outcomes In Peruvian Patients, Giljae Lee, Bruce A Rosa, Martha V Fernandez-Baca, John Martin, Rodrigo A Ore, Pedro Ortiz, Miguel M Cabada, Makedonka Mitreva

2020-Current year OA Pubs

BACKGROUND:

METHODS: In this study, we investigated the relationship between

RESULTS AND DISCUSSION: Infection was associated with specific microbial taxonomic and functional features, including higher abundance of

CONCLUSIONS: Our findings underscore the impact of helminth infection on gut microbiome and suggest a potential role of gut microbiota in modulating TCBZ efficacy, offering novel insights into

Microbiota Dynamics During Ascaris Suum Larval Migration: Implications For Host Microbial Communities In A Murine Model, Sergio Castañeda, Cristina Poveda, Charlie Suarez-Reyes, Yifan Wu, Noah Haugen, Luz H Patiño, Jill E Weatherhead, Juan David Ramírez

Faculty, Staff and Students Publications

The complex interactions between parasites, their hosts, and associated microbiota hold significant implications for host health and disease outcomes. Helminths like Ascaris lumbricoides and Ascaris suum can significantly alter the host's intestinal microbiota, affecting both parasite biology and host pathology. Despite extensive research on host-microbiota changes due to helminth infections, the study of helminth-associated microbiota remains limited. This study aims to characterize the microbiota associated with Ascaris larvae and surrounding host tissues at distinct developmental stages (day 4, day 8, day 14), during larval migration through the liver, lungs, and intestine, and its impact on the host's microbiota in a …

A Murine Model Of Gestational Diabetes Reveals Masld Risk And Alterations In Markers Of Hepatic Mitochondrial Metabolism, Grace E Shryack, Alexa A Krause, Simone Hernandez Ruano, Laura C Schulz, Kathleen A Pennington, R Scott Rector

Faculty, Staff and Students Publications

Introduction: Gestational Diabetes Mellitus (GDM) impacts roughly 1 in 7 pregnancies and results in metabolic dysfunction-associated steatotic liver disease (MASLD) in 30% of these women. Nonetheless, there exists a dearth of investigation into the relationship between GDM and MASLD. Here, we sought to investigate the potential role of hepatic mitochondrial function in GDM and MASLD.

Methods: One week prior to conception and throughout pregnancy, mice were fed either a low-fat control diet (CD) or a high-fat, high-sucrose (HFHS) diet to induce an established model of GDM. Maternal livers were collected at day 0, 6.5, 13.5 and 17.5 of pregnancy. Hepatic …

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

Inhibition Of Nitric Oxide Synthase Transforms Carotid Occlusion-Mediated Benign Oligemia Into De Novo Large Cerebral Infarction, Ha Kim, Jinyong Chung, Jeong Wook Kang, Dawid Schellingerhout, Soo Ji Lee, Hee Jeong Jang, Inyeong Park, Taesu Kim, Dong-Seok Gwak, Ji Sung Lee, Sung-Ha Hong, Kang-Hoon Je, Hee-Joon Bae, Joohon Sung, Eng H Lo, James Faber, Cenk Ayata, Dong-Eog Kim

Faculty, Staff and Student Publications

No abstract provided.

Reproducibility And Repeatability Of 18f-(2s, 4r)-4-Fluoroglutamine Pet Imaging In Preclinical Oncology Models, Gregory D Ayers, Allison S Cohen, Seong-Woo Bae, Xiaoxia Wen, Alyssa Pollard, Shilpa Sharma, Trey Claus, Adria Payne, Ling Geng, Ping Zhao, Mohammed Noor Tantawy, Seth T Gammon, H Charles Manning

Faculty, Staff and Student Publications

Introduction: Measurement of repeatability and reproducibility (R&R) is necessary to realize the full potential of positron emission tomography (PET). Several studies have evaluated the reproducibility of PET using 18F-FDG, the most common PET tracer used in oncology, but similar studies using other PET tracers are scarce. Even fewer assess agreement and R&R with statistical methods designed explicitly for the task. 18F-(2S, 4R)-4-fluoro-glutamine (18F-Gln) is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in vivo research.

Methods: Twenty mice bearing colorectal cancer cell line xenografts were injected with ~9 …

Selective Inhibition Of Canonical Stat3 Signaling Suppresses K-Ras Mutant Lung Tumorigenesis And Reinvigorates Anti-Tumor Immunity, Michael J Clowers, Zahraa Rahal, Sung-Nam Cho, Avantika Krishna, Bo Yuan, Leticia G Hamana Zorrilla, T Kris Eckols, Moses M Kasembeli, Samuel Liu, Stephen Peng, Marco Ramos-Castaneda, Annamarie L Thompson, Carlos Ignacio Rodriguez Reyna, Katherine E Larsen, Maria T Grimaldo, Shanshan Deng, Nastaran Karimi, Cody Chou, Walter V Velasco, Melody Zarghooni, Sayan Alekseev, Luisa M Solis Soto, Edwin J Ostrin, Humam Kadara, Suhendan Ekmekcioglu, David J Tweardy, Seyed Javad Moghaddam

Faculty, Staff and Student Publications

Introduction: K-ras mutant lung adenocarcinoma (KM-LUAD) is a difficult-to-treat cancer subtype in which chronic inflammation pervades the tumor immune microenvironment (TIME). Pro-inflammatory pathways dampen the response to treatments, including immune checkpoint inhibitors, necessitating therapies that target this inflammatory signaling network in the TIME. One of the lynchpins of chronic inflammation in KM-LUAD is signal transducer and activator of transcription 3 (STAT3).

Methods: Here, we tested the anti-tumor and early immunotherapeutic efficacy of TTI-101, a selective small-molecule inhibitor of canonical STAT3 signaling, in a K-rasG12D mutant lung cancer mouse model (CC-LR).

Results: Treatment of CC-LR mice with TTI-101 resulted in reduced …

Anti-Cd137 Agonist Antibody-Independent And Clinically Feasible Preparation Of Tumor-Infiltrating Lymphocytes From Soft Tissue Sarcoma And Osteosarcoma, Yining Jin, Zhiliang Jia, Xueqing Xia, Nancy B Gordon, Joseph A Ludwig, Neeta Somaiah, Shulin Li

Faculty, Staff and Student Publications

Background: Tumor infiltrating lymphocytes (TILs) therapy has been proved for treatment of metastatic melanoma and is under investigation for other types of solid tumors. However, these successes are threatened by discontinued supply of GMP-grade anti-CD137 agonist, a key TIL preparation reagent. Therefore, exploring a GMP-adherent method for expanding endogenous TILs without anti-CD137 agonist is urgent. Toward this end, we aimed to establish an anti-CD137-independent and clinically feasible TIL expansion protocol to prepare TILs from under investigated sarcoma tumors.

Methods: We collected resected tumors from patients and cut tissues into fragments. We used IL-2 and T-cell activator CD3/CD28 without anti-CD137 agonist …

18 Kda Translocator Protein (Tspo) Is Upregulated In Rat Brain After Peripheral Nerve Injury And Downregulated By Diroximel Fumarate, Rafael A Cazuza, Sever M Zagrai, Anamaria R Grieco, Thomas D Avery, Andrew D Abell, Hsiao-Ying Wey, Marco L Loggia, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments. We used positron emission tomography-computed tomography (PET-CT) and [18F]-PBR06 radioligand to measure TSPO levels in the brain across time after chronic constriction injury (CCI) of the sciatic nerve in both male and female rats. Up to 10 weeks post-CCI, TSPO expression was …

E2f1 Overexpression Reduces Aging-Associated Dna Damage In Cultured Cerebral Endothelial Cells And Improves Cognitive Performance In Aged Mice, Sheelu Monga, Samantha Flores, Maria Pilar Blasco-Conesa, Syed M Rahman, Brian Noh, Pedram Peesh, Bhanu Priya Ganesh, Sean P Marrelli, Louise D Mccullough, Jose Felix Moruno-Manchon

Faculty, Staff and Student Publications

As we age, cerebral endothelial cells (CECs) are less efficient in maintaining genome integrity and accumulate DNA damage. DNA damage in the brain endothelium can lead to the impairment of the blood–brain barrier (BBB), which is a major factor in brain dysfunction and dementia. Thus, identifying factors that regulate DNA repair in the brain endothelium can prevent brain dysfunction associated with aging. E2F1 is a transcription factor that regulates the expression of genes associated with DNA repair, among other functions. We hypothesize that E2F1 is downregulated in the brain vasculature of mice with aging and that E2F1 upregulation can improve …

Organ Of Corti Macrophages: A Distinct Group Of Cochlear Macrophages With Potential Roles In Supporting Cell Degeneration And Survival, Mengxiao Ye, Celia Zhang, Dalian Ding, Guang-Di Chen, Henry J Adler, Rania Sharaf, Bo Hua Hu

Faculty, Staff and Student Publications

Macrophages are the primary immune cells in the cochlea, essential for maintaining cochlear homeostasis and orchestrating inflammatory responses to pathological events. Although these cells have been found in various parts of the cochlea, their presence in the organ of Corti, a critical structure for acoustic sensing, remains poorly understood. The present study was designed to examine macrophage responses to ototoxic drug-induced cochlear damage and age-related cochlear degeneration, with a particular focus on the pathological conditions that trigger macrophage recruitment into the organ of Corti. We used a model of ototoxicity induced by cyclodextrin, a cyclic oligosaccharide known for its ability …

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin

A Cytotoxic Peptide-Drug Conjugate For Tumor-Specific Delivery Of Co-Injected Molecules, Norio Miyamura, Chisato M Yamazaki, Yasuaki Anami, Kyoji Tsuchikama, Kazuki N Sugahara

Faculty, Staff and Student Publications

An ideal cancer therapy enhances anti-tumor effects while minimizing side effects. iRGD, a non-cytotoxic peptide that activates a tumor-specific molecular transport machinery, promotes the penetration of co-injected drugs into tumor tissues. Clinical trials have demonstrated its potential as a tumor-specific delivery scaffold and potentiator of anti-cancer agents. In this study, we synthesized an iRGD conjugate containing monomethyl auristatin F (MMAF), a highly toxic antimitotic agent, and characterized its dual function as a tumor-specific cytotoxic agent and co-injected drug delivery scaffold. The iRGD-MMAF conjugate internalized and killed cultured tumor cells in an αv integrin-dependent manner. When injected systemically, iRGD-MMAF homed selectively …

Distribution Of Chronic Wasting Disease (Cwd) Prions In Tissues From Experimentally Exposed Coyotes (Canis Latrans), Nancy Ho, Reece Mcginn, Paulina Soto, Terry R Spraker, Justin Fischer, Kurt Vercauteren, Tracy Nichols, Rodrigo Morales

Faculty, Staff and Student Publications

Cervids susceptible to chronic wasting disease (CWD) are sympatric with multiple other animal species that can interact with infectious prions. Several reports have described the susceptibility of other species to CWD prions, or their potential to transport them. One of these species is the coyote (Canis latrans), which has been previously shown to pass transmission-relevant prion titers in their feces for at least three days after ingesting prion-positive brain material. The current study followed up on these findings and evaluated the distribution of prions in multiple tissues from the same coyotes. Our results show that prions persist in the digestive …

Peripheral Administration Of Blood From Tau Transgenic Animals Exacerbates Brain Tau-Associated Pathology, Laura Vegas-Gomez, Matias Pizarro, Jesus Garcia-Martin, Maria Angeles Arredondo-Alcala, Bianca Bustamante, Carolina Gonzalez-Silva, Soledad Matus, Rodrigo Diaz-Espinoza, Antonia Gutierrez, Rodrigo Morales, Claudia Duran-Aniotz, Ines Moreno-Gonzalez

Faculty, Staff and Student Publications

The accumulation of amyloid plaques and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD). While amyloid-beta propagation through prion-like mechanisms has been extensively studied in both central and peripheral pathways, the potential spreading of tau aggregates in the periphery remains largely unexplored. Emerging evidence suggests that hyperphosphorylated tau (ptau) aggregates may propagate beyond the central nervous system, as they have been detected in peripheral tissues and biological fluids from humans and mouse models of tauopathies. However, whether peripheral ptau aggregates or other factors associated to its accumulation contribute to brain pathology remains unclear. In this study, we investigate the …

Exacerbation Of Paclitaxel-Induced Neuropathic Pain Behaviors In Breast Tumor-Bearing Mice, Hee Kee Kim, Juping Xing, Youn-Sang Jung, Jae-Il Park, Hee Young Kim, Jimin Kim, Salahadin Abdi

Faculty, Staff and Student Publications

Background: Chronic pain and cancer interact bidirectionally, with pain enhancing sensory peptides and potentially promoting tumor growth. Despite this, most chemotherapy-induced neuropathic pain (CIPN) studies overlook the contribution of cancer itself to neuropathy, focusing instead on chemotherapy-induced mechanisms. Animal models of chemotherapy-induced neuropathic pain (CINP) have been developed by injecting chemotherapeutic drugs such as paclitaxel into normal animals without cancer. This study aimed to develop a new model in mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mice, a widely used breast cancer model with normal immune function.

Results: The percentage of positive response (PPR) of paclitaxel-injected MMTV-PyMT mice increased …

Development Of Microcystoid Macular Degeneration In The Retina Of Nonhuman Primates: Time-Course And Associated Pathologies, Thomas C M Lavery, Carol A Rasmussen, Alexander W Katz, Charlene B Y Kim, James N Ver Hoeve, Paul E Miller, Peter J Sonnentag, Brian J Christian, Christopher J Murphy, David R Piwnica-Worms, Seth T Gammon, Xudong Qiu, Paul L Kaufman, T Michael Nork

Faculty, Staff and Student Publications

Purpose: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.

Methods: Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous …

The Primary Cilia: Orchestrating Cranial Neural Crest Cell Development, Hiroyuki Yamaguchi, Matthew D Meyer, William B Barrell, Maryam Faisal, Rebecca Berdeaux, Karen J Liu, Yoshihiro Komatsu

Faculty, Staff and Student Publications

Primary cilia (hereafter "cilia") are microtubule-based antenna-like organelles projecting from the surface of vertebrate cells. Cilia can serve as cellular antennae controlling cell growth and differentiation. Absent or dysfunctional cilia frequently lead to craniofacial anomalies known as craniofacial ciliopathies. However, the detailed pathological mechanisms of craniofacial ciliopathies remain unclear. This perspective discusses our current understanding of the role of cilia in cranial neural crest cells. We also describe potential mechanisms of ciliogenesis in cranial neural crest cells, which may contribute to unraveling the complex pathogenesis of craniofacial ciliopathies.

Immune Responses In Rodent Whole Eye Transplantation: Elucidation And Preliminary Investigations Into Rejection Diagnosis And Monitoring, Bing Li, Yong Wang, Charles R Owens, Touka Banaee, Charleen T Chu, Kayvon Jabbari, Anna D Lee, Neil J Khatter, Alan G Palestine, An-Jey A Su, Christene A Huang, Kia M Washington

Faculty, Staff and Student Publications

Background: Whole Eye Transplantation (WET) offers potential for vision restoration but is hindered by the complex challenge of immune rejection. Understanding and closely monitoring these immunological responses is crucial for advancing WET. This study delves into the timeline and nature of immune responses in a rodent model of WET without immunosuppression, aiming to elucidate a detailed picture of the immune landscape post-transplantation and establish innovative diagnostic and monitoring methods.

Methods: We employed a multi-faceted approach to analyze immune responses post-WET, including assessments of gross changes in corneal transparency, thickness, and skin condition. Histopathological examinations of both ocular and surrounding skin …

Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated calcium (Ca2+) entry (SOCE) represents a major route of Ca2+ permeation across the plasma membrane (PM) in non-excitable cells, which plays an indispensable role in maintaining intracellular Ca2+ homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca2+ sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca2+ stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to translocation of STIM1-containing ER membrane towards the PM. This movement is facilitated by the physical interaction between positively charged cytosolic domains within STIM1 and negatively charged phospholipids embedded in the PM, …

Isatuximab For The Treatment Of Multiple Myeloma: Current Clinical Advances And Future Directions, Paul G Richardson, Elisabeth K O'Donnell, Peter O'Gorman, Lisa B Leypoldt, Jacob Laubach, Francesca Gay, Xavier Leleu, Thierry Facon, Philippe Moreau, Meletios A Dimopoulos, Hartmut Goldschmidt, Elias K Mai, Michele Cavo, Katja C Weisel, Jesus G Berdeja, Robert Z Orlowski, Meral Beksaç, Aurore Perrot, Joseph Mikhael, Thomas Martin

Faculty, Staff and Student Publications

Introduction: The addition of the anti-CD38 monoclonal antibody isatuximab to standard therapies is transforming the care of patients with newly diagnosed multiple myeloma (NDMM), as previously seen in the relapsed/refractory setting. This is particularly important for patients with NDMM as early treatment with effective, well tolerated therapies may ensure better clinical outcomes.

Areas covered: Here, we examine recent results from pivotal Phase 3 and 2 clinical trials that demonstrate efficacy and safety of isatuximab across multiple combinations, for both transplant-ineligible and transplant-eligible NDMM patients. We then evaluate long-term outcomes from the IKEMA and ICARIA-MM trials as well as real-world evidence …

Predicting Sinonasal Inverted Papilloma Attachment Using Machine Learning: Current Lessons And Future Directions, Sean P Mckee, Xiaomin Liang, William C Yao, Brady Anderson, Jumah G Ahmad, David Z Allen, Salman Hasan, Andy J Chua, Chinmay Mokashi, Samia Islam, Amber U Luong, Martin J Citardi, Luca Giancardo

Faculty, Staff and Student Publications

Background: Hyperostosis is a common radiographic feature of inverted papilloma (IP) tumor origin on computed tomography (CT). Herein, we developed a machine learning (ML) model capable of analyzing CT images and identifying IP attachment sites.

Methods: A retrospective review of patients treated for IP at our institution was performed. The tumor attachment site was manually segmented on CT scans by the operating surgeon. We used a nnU-Net model, a state-of-the-art deep learning-based segmentation algorithm that automatically configures image preprocessing, network architecture, training, and post-processing to identify the IP attachment site. The model was trained and evaluated using a 5-fold cross …