Medicine and Health Sciences Commons^™

Sox On Tumors, A Comfort Or A Constraint?, Junqing Jiang, Yufei Wang, Mengyu Sun, Xiangyuan Luo, Zerui Zhang, Yijun Wang, Siwen Li, Dian Hu, Jiaqian Zhang, Zhangfan Wu, Xiaoping Chen, Bixiang Zhang, Xiao Xu, Shuai Wang, Shengjun Xu, Wenjie Huang, Limin Xia

Faculty, Staff and Student Publications

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes …

Functional Epas1/ Hif2a Missense Variant Is Associated With Hematocrit In Andean Highlanders, Elijah S Lawrence, Wanjun Gu, Ryan J Bohlender, Cecilia Anza-Ramirez, Amy M Cole, James J Yu, Hao Hu, Erica C Heinrich, Katie A O'Brien, Carlos A Vasquez, Quinn T Cowan, Patrick T Bruck, Kysha Mercader, Mona Alotaibi, Tao Long, James E Hall, Esteban A Moya, Marco A Bauk, Jennifer J Reeves, Mitchell C Kong, Rany M Salem, Gustavo Vizcardo-Galindo, Jose-Luis Macarlupu, Rómulo Figueroa-Mujíca, Daniela Bermudez, Noemi Corante, Eduardo Gaio, Keolu P Fox, Veikko Salomaa, Aki S Havulinna, Andrew J Murray, Atul Malhotra, Frank L Powel, Mohit Jain, Alexis C Komor, Gianpiero L Cavalleri, Chad D Huff, Francisco C Villafuerte, Tatum S Simonson

Faculty, Staff and Student Publications

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations …

Comprehensive Landscape Of Braf Variant Classes, Clonalities, And Co-Mutations In Metastatic Colorectal Cancer Using Ctdna Profiling, Benny Johnson, Van Morris, Xuemei Wang, Arvind Dasari, Kanwal Raghav, John Paul Shen, Michael S Lee, Ryan Huey, Christine Parseghian, Jason Willis, Robert Wolff, Leylah M Drusbosky, Michael J Overman, Scott Kopetz

Faculty, Staff and Student Publications

Although V600E accounts for the majority of the BRAF mutations in metastatic colorectal cancer (mCRC), non-V600 BRAF variants have been shown in recent years to represent a distinct molecular subtype. This study provides a comprehensive profile of BRAF variants in mCRC using a large genomic database of circulating tumor DNA (ctDNA) and analyzing clinical outcomes in a cohort of patients with atypical (non-V600) BRAF variants (aBRAF; class II, class III, unclassified). Overall, 1733 out of 14,742 mCRC patients in the ctDNA cohort had at least one BRAF variant. Patients with atypical BRAF variants tended to be younger and …

Investigating The Genetic Makeup Of The Major Histocompatibility Complex (Mhc) In The United Arab Emirates Population Through Next-Generation Sequencing, Nour A. D. Marzouka, Halima Alnaqbi, Amira Al-Aamri, Guan Tay, Habiba Alsafar

Research outputs 2022 to 2026

The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the …

Impact Of Equine Interaction During Psychotherapy On Anxiety And Depression For Residential Treatment Program Patients Experiencing Substance Withdrawal, Molly M. Friend, Molly C. Nicodemus, Clay Cavinder, Caleb Lemley, Pauline Prince, Katherine A. Cagle-Holtcamp, Rebecca M. Swanson

People and Animals: The International Journal of Research and Practice

As incidences of substance use disorders (SUD) increase in the wake of the COVID-19 pandemic, there is a need for more effective treatment approaches. Further, treatment approaches currently available struggle to retain patients during the period of substance withdrawal in early treatment due to patients’ withdrawal symptoms including increased feelings of anxiety and depression. Withdrawal symptoms have been linked to dysregulated cortisol concentrations present in this period. Psychotherapy incorporating equine interaction (PIE) has emerged in other populations as a treatment that decreases cortisol concentrations and improves treatment retention. The present study investigated the impact of 4 weeks of PIE on …

Correction To: Should We Use Rifampicin In Periprosthetic Joint Infections Caused By Staphylococci When The Implant Has Been Exchanged? A Multicenter Observational Cohort Study, Tobias Siegfried Kramer, Alex Soriano, Sarah Tedeschi, Antonia Chen, Pierre Tattevin, Eric Senneville, Joan Gomez-Junyent, Victoria Birlutiu, Sabine Petersdorf, Vicens Diaz De Brito, Ignacio Sancho Gonzalez, Katherine Belden, Marjan Wouthuyzen-Bakker

Division of Infectious Diseases and Environmental Medicine Faculty Papers

No abstract provided.

Prex1 Improves Homeostatic Proliferation To Maintain A Naive Cd4+ T Cell Compartment In Older Age, Huimin Zhang, Hirohisa Okuyama, Abhinav Jain, Rohit R Jadhav, Bowen Wu, Ines Sturmlechner, Jose Morales, Shozo Ohtsuki, Cornelia M Weyand, Jӧrg J Goronzy

Faculty, Staff and Student Publications

The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4+ T cell compartment into older age. Here, we describe that naive CD4+ T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic …

Impact Of An Integrated Health, Nutrition, And Early Child Stimulation And Responsive Care Intervention Package Delivered To Preterm Or Term Small For Gestational Age Babies During Infancy On Growth And Neurodevelopment: Study Protocol Of An Individually Randomized Controlled Trial In India (Small Babies Trial), Ranadip Chowdhury, Rukman Manapurath, Ingvild Fossgard Sandøy, Ravi Prakash Upadhyay, Neeta Dhabhai, Saijuddin Shaikh, Harish Chellani, Tarun Shankar Choudhary, Abhinav Jain, Jose Martines, Nita Bhandari, Tor A Strand, Sunita Taneja

Faculty, Staff and Student Publications

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating.

METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata …

Three-Year Follow-Up Analysis Of Axicabtagene Ciloleucel In Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (Zuma-5), Sattva S Neelapu, Julio C Chavez, Alison R Sehgal, Narendranath Epperla, Matthew Ulrickson, Emmanuel Bachy, Pashna N Munshi, Carla Casulo, David G Maloney, Sven De Vos, Ran Reshef, Lori A Leslie, Olalekan O Oluwole, Ibrahim Yakoub-Agha, Rashmi Khanal, Joseph Rosenblatt, Ronald Korn, Weixin Peng, Christine Lui, Jacob Wulff, Rhine Shen, Soumya Poddar, A Scott Jung, Harry Miao, Sara Beygi, Caron A Jacobson

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR …

The Mrna-Lnp Vaccines - The Good, The Bad And The Ugly?, Botond Z. Igyártó, Zhen Qin

Department of Microbiology and Immunology Faculty Papers

The mRNA-LNP vaccine has received much attention during the COVID-19 pandemic since it served as the basis of the most widely used SARS-CoV-2 vaccines in Western countries. Based on early clinical trial data, these vaccines were deemed safe and effective for all demographics. However, the latest data raise serious concerns about the safety and effectiveness of these vaccines. Here, we review some of the safety and efficacy concerns identified to date. We also discuss the potential mechanism of observed adverse events related to the use of these vaccines and whether they can be mitigated by alterations of this vaccine mechanism …

Evolving Therapies, Neurocognitive Outcomes, And Functional Independence In Adult Survivors Of Childhood Glioma, Chiara Papini, Sedigheh Mirzaei S, Mengqi Xing, Ingrid Tonning Olsson, Peter M K De Blank, Katharine R Lange, Ralph Salloum, Deokumar Srivastava, Wendy M Leisenring, Rebecca M Howell, Kevin C Oeffinger, Leslie L Robison, Gregory T Armstrong, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

Background: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown.

Methods: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with …

Targeting Dna2 Overcomes Metabolic Reprogramming In Multiple Myeloma, Natthakan Thongon, Feiyang Ma, Natalia Baran, Pamela Lockyer, Jintan Liu, Christopher Jackson, Ashley Rose, Ken Furudate, Bethany Wildeman, Matteo Marchesini, Valentina Marchica, Paola Storti, Giannalisa Todaro, Irene Ganan-Gomez, Vera Adema, Juan Jose Rodriguez-Sevilla, Yun Qing, Min Jin Ha, Rodrigo Fonseca, Caleb Stein, Caleb Class, Lin Tan, Sergio Attanasio, Guillermo Garcia-Manero, Nicola Giuliani, David Berrios Nolasco, Andrea Santoni, Claudio Cerchione, Carlos Bueso-Ramos, Marina Konopleva, Philip Lorenzi, Koichi Takahashi, Elisabet Manasanch, Gabriella Sammarelli, Rashmi Kanagal-Shamanna, Andrea Viale, Marta Chesi, Simona Colla

Faculty, Staff and Student Publications

DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identify the mitochondrial DNA repair protein …

Assessment Of Human Leukocyte Antigen-Based Neoantigen Presentation To Determine Pan-Cancer Response To Immunotherapy, Jiefei Han, Yiting Dong, Xiuli Zhu, Alexandre Reuben, Jianjun Zhang, Jiachen Xu, Hua Bai, Jianchun Duan, Rui Wan, Jie Zhao, Jing Bai, Xuefeng Xia, Xin Yi, Chao Cheng, Jie Wang, Zhijie Wang

Faculty, Staff and Student Publications

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built …

The Transmission Of Oropharyngeal Squamous Cell Carcinoma, Kunjal Patel, Aleesha Thomas

Mako: NSU Undergraduate Student Journal

The existence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has recently been found to have correlations with the Human Papillomavirus. HPV-associated OPSCC exhibits a unique method of infection and transmission and has made this branch an emerging disease in the recent decade. This systematic review of the literature was conducted to further explore research into Oropharyngeal Squamous Cell Cancer (OPSCC). Commonly referred to as “throat cancer”, this growth originates in the oropharynx. Symptoms of this condition include sore throat, lumps in the neck, and difficulty with swallowing. OPSCC has many variants but has shown a strong association with Human Papillomavirus (HPV), …

Zika Virus Microcephaly: Predicting The Symptoms Of Microcephaly So Families Can Prepare, Eleanor J. Wind

Mako: NSU Undergraduate Student Journal

Microcephaly is a rare congenital defect where the circumference of an infants head is smaller than average. The cause is unknown and the risk factors and symptoms of microcephaly are wide ranging. One risk factor is exposure during pregnancy to viruses such as the Zika virus.. A recent study was conducted on infants who were born with Zika virus Microcephaly following the Zika outbreak in Brazil. The researchers conducted MRI scans and developmental testing. Then an algorithm to predict behavioral outcomes of Zika Virus Microcephaly was successfully created. This research will benefit caretakers of infants with Zika virus Microcephaly by …

History Of Clover Leaf Syndrome, Isabella Perez

Mako: NSU Undergraduate Student Journal

The purpose of this paper is to summarize the history of clover leaf syndrome and describe the newest advancements made to treat it. Clover leaf syndrome is more formally referred to as Kleeblattschadel syndrome. Information was gathered from several scholarly, peer-reviewed articles, and was condensed down into the key takeaways. This syndrome impacts the formation of the skull due to premature fusion of its sutures, creating a tri-lobar skull that resembles a clover leaf. This premature fusion is referred to as a type of craniosynostosis and has been linked to causing several other health complications ranging in severity. This is …

Recent Studies In The Surgical Treatment Of Tetralogy Of Fallot, Emma C. Gardner

Mako: NSU Undergraduate Student Journal

No abstract provided.

Encephaloceles: A Comprehensive Exploration Of Research, Causes, Prevention, And Innovative Approaches To Diagnosis And Treatment, Amanda N. Bautista

Mako: NSU Undergraduate Student Journal

Encephaloceles, a rare medical condition derived from Greek words meaning "brain hernia," involve the protrusion of brain tissue, cerebrospinal fluid, or membranes through a defect in the skull. These anomalies often present at birth and can occur in various locations on the skull. Recent research has shed light on the possible causes of encephaloceles, including genetic factors such as the Sonic Hedgehog pathway and inadequate folic acid intake during pregnancy. Folic acid is essential for proper neural tube closure during fetal development, making it a key preventive measure.

Emerging treatments for encephaloceles show promise, with a focus on mesenchymal stem …

Transcription Factor Bach1 In Cancer: Roles, Mechanisms, And Prospects For Targeted Therapy, Dian Hu, Zerui Zhang, Xiangyuan Luo, Siwen Li, Junqing Jiang, Jiaqian Zhang, Zhangfan Wu, Yijun Wang, Mengyu Sun, Xiaoping Chen, Bixiang Zhang, Xiao Xu, Shuai Wang, Shengjun Xu, Yufei Wang, Wenjie Huang, Limin Xia

Faculty, Staff and Student Publications

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status …

Patient And Dentist Perspectives On Collecting Patient Reported Outcomes After Painful Dental Procedures In The National Dental Pbrn, Elsbeth Kalenderian, Sayali Tungare, Urvi Mehta, Sharmeen Hamid, Rahma Mungia, Alfa-Ibrahim Yansane, David Holmes, Kim Funkhouser, Ana M Ibarra-Noriega, Janelle Urata, D Brad Rindal, Heiko Spallek, Joel White, Muhammad F Walji

Faculty, Staff and Student Publications

BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patient's subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice.

METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators.

RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patient's pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. …

Androgen Drives Melanoma Invasiveness And Metastatic Spread By Inducing Tumorigenic Fucosylation, Qian Liu, Emma Adhikari, Daniel K Lester, Bin Fang, Joseph O Johnson, Yijun Tian, Andrea T Mockabee-Macias, Victoria Izumi, Kelly M Guzman, Michael G White, John M Koomen, Jennifer A Wargo, Jane L Messina, Jianfei Qi, Eric K Lau

Faculty, Staff and Student Publications

Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic …

Diaphragmatic Breathing Influences Recovery Metrics After Aerobic Exercise, Trace L. Cruz

Masters Theses

Recovery from aerobic exercise is multifaceted and highly complex. Recovery includes cellular repair, substrate availability, autonomic nervous system status, and many other factors that comprise homeostasis. The present study is designed to assess the influence of diaphragmatic breathing after aerobic exercise to exhaustion. Diaphragmatic breathing is deep rhythmical breathing that is known to influence the autonomic nervous system, specifically through cranial nerve X (Vagus nerve). Subjects (n=12, age = 22.3±1.15 years old, height = 67.882.17 inches, weight =154.4515.20 pounds, BF% = 15.785.43). Performed four VO2max tests on two different days (2 each day). On each day, subjects performed a 20:00 …

The Hsp90-Myc-Cdk9 Network Drives Therapeutic Resistance In Mantle Cell Lymphoma, Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph Mcintosh, Zhihong Chen, Jovanny Vargas, Lei Nie, Yixin Yao, Heng-Huan Lee, Wei Wang, Johnnelson R Bigcal, Maria Badillo, Jitendra Meena, Christopher Flowers, Jia Zhou, Zhongming Zhao, Lukas M Simon, Michael Wang

Faculty, Staff and Student Publications

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 …

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

Aspscr1-Tfe3 Reprograms Transcription By Organizing Enhancer Loops Around Hexameric Vcp/P97, Amir Pozner, Li Li, Shiv Prakash Verma, Shuxin Wang, Jared J Barrott, Mary L Nelson, Jamie S E Yu, Gian Luca Negri, Shane Colborne, Christopher S Hughes, Ju-Fen Zhu, Sydney L Lambert, Lara S Carroll, Kyllie Smith-Fry, Michael G Stewart, Sarmishta Kannan, Bodrie Jensen, Cini M John, Saif Sikdar, Hongrui Liu, Ngoc Ha Dang, Jennifer Bourdage, Jinxiu Li, Jeffery M Vahrenkamp, Katelyn L Mortenson, John S Groundland, Rosanna Wustrack, Donna L Senger, Franz J Zemp, Douglas J Mahoney, Jason Gertz, Xiaoyang Zhang, Alexander J Lazar, Martin Hirst, Gregg B Morin, Torsten O Nielsen, Peter S Shen, Kevin B Jones

Faculty, Staff and Student Publications

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its …

Antibody-Conjugated Polymersomes With Encapsulated Indocyanine Green J-Aggregates And High Near-Infrared Absorption For Molecular Photoacoustic Cancer Imaging, Mohammed R Kawelah, Sangheon Han, Ceren Atila Dincer, Jongyeong Jeon, Joel Brisola, Aasim F Hussain, Ananthakrishnan S Jeevarathinam, Richard Bouchard, Alexander E Marras, Thomas M Truskett, Konstantin V Sokolov, Keith P Johnston

Faculty, Staff and Student Publications

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-

An Excitatory Projection From The Basal Forebrain To The Ventral Tegmental Area That Underlies Anorexia-Like Phenotypes, Jing Cai, Yanyan Jiang, Yuanzhong Xu, Zhiying Jiang, Claire Young, Hongli Li, Joshua Ortiz-Guzman, Yizhou Zhuo, Yulong Li, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of …

A Reliable Diabetic Retinopathy Grading Via Transfer Learning And Ensemble Learning With Quadratic Weighted Kappa Metric, Sai Venkatesh Chilukoti, Liqun Shan, Vijay Srinivas Tida, Anthony S. Maida, Xiali Hei

Computer Science Faculty Publications

The most common eye infection in people with diabetes is diabetic retinopathy (DR). It might cause blurred vision or even total blindness. Therefore, it is essential to promote early detection to prevent or alleviate the impact of DR. However, due to the possibility that symptoms may not be noticeable in the early stages of DR, it is difficult for doctors to identify them. Therefore, numerous predictive models based on machine learning (ML) and deep learning (DL) have been developed to determine all stages of DR. However, existing DR classification models cannot classify every DR stage or use a computationally heavy …

Dynamic Prognosis Prediction For Patients On Dapt After Drug-Eluting Stent Implantation: Model Development And Validation, Fang Li, Laila Rasmy, Yang Xiang, Jingna Feng, Ahmed Abdelhameed, Xinyue Hu, Zenan Sun, David Aguilar, Abhijeet Dhoble, Jingcheng Du, Qing Wang, Shuteng Niu, Yifang Dang, Xinyuan Zhang, Ziqian Xie, Yi Nian, Jianping He, Yujia Zhou, Jianfu Li, Mattia Prosperi, Jiang Bian, Degui Zhi, Cui Tao

Faculty, Staff and Student Publications

BACKGROUND: The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management.

METHODS AND RESULTS: We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were …

Tumor-Associated Antigen Targets For Novel Immune-Based Strategies In Prostate Cancer, Amman Bhasin, Patrick Mille, Aditya Eturi, Andrew Iskander, William Tester, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Prostate cancer remains the most common malignancy among men in the United States. Advancements in androgen receptor signaling blockade have led to landmark approvals for its use in patients with locally advanced and metastatic disease. However, additional novel therapeutic strategies for both hormone-sensitive and castration-resistant diseases remain ongoing areas of study. Thus, we turn to the growth of immuno-oncology, which has led to improved treatment outcomes for a variety of hematologic and solid tumor malignancies. Prostate cancers have shown only modest results with immune checkpoint inhibition in published trials, and innovative strategies are now looking into enhancing cytotoxic T-cell activity …