Medical Specialties Commons^™

Associations Between Retinal Nerve Fiber Layer Thickness And Cerebral Small Vessel Disease, Alexa E. Nichols, Silvia Mejia-Arango, Jorge Igor Zwir, Andrew Tsin, Lorena Flores-Hernandez, Eron G. Manusov, Gladys E. Maestre, Amin Ibrahim, Tori Sayers, Jesus Melgarejo

Research Colloquium

Introduction: Cerebral small vessel disease (CSVD) is a major vascular contributor to cognitive impairment and dementia. CSVD affects the deep and subcortical cerebral white matter.^1,2 The retinal nerve fiber layer (RNFL) and cerebral white matter share a common embryological origin, with RNFL ganglion cell axons structurally analogous to cerebral white matter tracts.^3,4 This connection creates an opportunity to investigate whether structural changes in the RNFL reflect pathological changes in the cerebral white matter.^3,5,6 While most studies examining the relationship between RNFL and CSVD focus on specific comorbidities (e.g., patients with stroke or with cognitive impairment)^2,6,7,8, …

Decreased Risk Of Incident Cancer Among Patients With Vitiligo: A Multicenter Retrospective Cohort Analysis, Rahib K. Islam, Ivan D. Nguyen, Kazi N. Islam, Lacey M. Falgout, Jonathan M. Joseph, Collins T. Langley, Christopher J. Haas

School of Medicine Faculty Publications

No abstract provided.

Current States In Understanding Oligodendroglia-Mediated Neurological Issues In Neurofibromatosis Type 1 (Nf1), Benjamin E Aghoghovwia, Cheng-En Shen, Sabiha Bano, Nandini Shyamala, Alesandra Echeandia Marrero, Khushboo Irshad, Samer Sharafaldin, Nicole M Brossier, Yuan Pan

Faculty, Staff and Student Publications

Neurofibromatosis type 1 (NF1) is among the most common neurogenetic disorders and is associated with an increased risk of developing tumors in the nervous system. Additionally, up to 80% of patients with NF1 experience neurological complications, including deficits in attention, memory, and executive function. Significant effort has been dedicated to studying how NF1 mutations autonomously dysregulate neuronal function. Increasing evidence indicates that NF1 mutations also dysregulate the oligodendroglial lineage that contributes to neurological issues in NF1. Here, we summarize our current understanding of how NF1 mutations impact the oligodendroglial lineage homeostasis and plasticity. We also discuss gaps in knowledge, potential …

Functional Outcomes In Pediatric Patients On Renal Replacement Therapy In A Worldwide Registry, Kristin J Dolan, Katja M Gist, Abby Basalely, Gabriella Bottari, Abhishek Chakraborty, Mihaela Damian, Dana Fuhrman, Denise C Hasson, Catherine Joseph, Dave Kwiatkowski, Susan Martin, Jenn Nhan, Nicolas Ollberding, David T Selewski, Danielle Soranno, Michelle C Starr, Amy Strong, Sameer Thadani, Huaiyu Zang, Ayse Akcan Arikan

Faculty, Staff and Students Publications

Background and hypothesis: Mortality rates of children supported with continuous renal replacement therapy (CRRT) have improved, yet morbidity remains high. We aimed to evaluate the functional outcomes of children receiving CRRT using Functional Status Scale (FSS). We hypothesized that children receiving CRRT will have worse FSS compared with their baseline and acquire new morbidity at hospital discharge and 6 and 12 months post-discharge, and that lack of renal recovery will contribute to worsening functional status.

Methods: This is a retrospective chart review from The Worldwide Exploration of Renal Replacement Outcomes Collaborate in Kidney Disease (WE-ROCK), an international multi-center registry. Twenty-eight …

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And Adverse Clinical Outcomes In Patients With Pulmonary Hypertension And Chronic Kidney Disease, Andrew Geller, Jose Manuel Martinez Manzano, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Simone Jarrett, Kevin Bryan Lo, Christian Witzke

Einstein Health Papers

Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's J statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between …

Microtia, Peng You, Yi-Chun Liu, Caitlin Symonette

Faculty, Staff and Students Publications

No abstract provided.

Kmt2d Temporally Activates Neuronal Transcriptional Factor Genes To Mediate Cerebellar Granule Cell Differentiation, Shilpa S Dhar, Kyung-Pil Ko, Jinho Jang, Calena Brown-Abel, Tao Lin, Sharad Awasthi, Kaifu Chen, Roy V Sillitoe, Jae-Il Park, Min Gyu Lee

Duncan NRI Faculty and Staff Publications

Spatiotemporal gene expression is the fundamental feature of cellular differentiation, including neuron differentiation. The epigenetic mechanism underlying spatiotemporal gene regulation during in vivo neuron differentiation remains largely unknown. Granule cells (GCs) constitute the vast majority of neurons in the cerebellum, which contains most of neurons in the brain. Here, we show that

Association Between Therapeutic Alliance And Clinical Outcomes In Virtual Telepsychiatry: A Retrospective Analysis Of Data From Talkiatry, Cheryl Person, Nathaniel David Phillips, Kartik Venkatachalam, Georgia Gaveras

Faculty, Staff and Student Publications

Background: Given the increasing demand for accessible mental health services, fully virtual telepsychiatry has become a vital component of modern health care delivery. Therapeutic alliance, the collaborative and affective bond between patients and therapists, is a well-established predictor of clinical outcomes in traditional face-to-face and teletherapy. However, the relationship between therapeutic alliance and clinical outcomes in an outpatient telepsychiatry setting remains less understood.

Objective: Our primary objective was to evaluate the relationship between therapeutic alliance and clinical outcomes for depression and anxiety in an outpatient telepsychiatry practice.

Methods: This retrospective study analyzed data from treatment-seeking adults receiving services from Talkiatry, …

Aging In Mice Alters Regionally Enriched Striatal Astrocytes, Kay E Linker, Violeta Duran-Laforet, Matthias Ollivier, Xinzhu Yu, Dorothy P Schafer, Baljit S Khakh

Faculty, Staff and Student Publications

Aging affects multiple organs and within the brain drives distinct molecular changes across different cell types. The striatum encodes motor behaviors that decline with age, but our understanding of how cells within the striatum change remains incomplete. Using single-cell RNA sequencing from young and aged mice we identify molecularly distinct astrocyte subtypes. We show that astrocytes change significantly with age, exhibiting downregulation of genes, reduced diversity, and a shift to more homogenous inflammatory transcriptomic profiles. By exploring where striatal astrocyte subtypes are located with single-cell resolution, we map astrocytes enriched in dorsal, medial, and ventral striatum. Age increases inflammatory marker …

Comparison Of Imaging Based Single-Cell Resolution Spatial Transcriptomics Profiling Platforms Using Formalin-Fixed Paraffin-Embedded Tumor Samples, Nejla Ozirmak Lermi, Max Molina Ayala, Sharia Hernandez, Wei Lu, Khaja Khan, Alejandra Serrano, Idania Lubo, Leticia Hamana, Katarzyna Tomczak, Sean Barnes, Jinzhuang Dou, Qingnan Liang, Rti Team, Maria Gabriela Raso, Ximing Tang, Mei Jiang, Beatriz Sanchez-Espiridion, Annikka Weissferdt, John Heymach, Jianjun Zhang, Boris Sepesi, Tina Cascone, Anne Tsao, Mehmet Altan, Reza Mehran, Don Gibbons, Ignacio Wistuba, Cara Haymaker, Ken Chen, Luisa M Solis Soto

Faculty, Staff and Student Publications

Imaging-based spatial transcriptomics (ST) is evolving as a pivotal technology in studying tumor biology and associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. We use serial 5 μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma samples in tissue microarrays to compare the performance of the ST platforms (CosMx, MERFISH, and Xenium (uni/multi-modal)) in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx, and hematoxylin and eosin staining data. In addition to an objective assessment of automatic cell segmentation and phenotyping, we …

Heart Failure Devices: Treatment Options, Underutilization, And A Proposed Trigger System For Patient Referral And Evaluation, Marat Fudim, Dmitry M Yaranov, Richa Gupta, Laurie Letarte, Samuel F Sears, Brian G Howard, Nir Uriel, Vikram Raje, Kiran Mahmood, Sean P Pinney, Amin Yehya, Amit Alam, Pujan Patel, Albert Hicks, Amarinder Bindra, Steve M Antoine, Jason Feliberti, Allman Rollins, Vishal N Rao, Patrick Mccann, Nirav Raval, Rachel A Garcia, Ahmed Sayed

Faculty, Staff and Students Publications

The use of guideline-directed medical therapy (GDMT) has substantially prolonged and improved the lives of patients with heart failure (HF). Nevertheless, adherence rates remain suboptimal. Even when successfully maximized and adhered to, there is a substantial residual risk of recurrent HF hospitalization and death. In light of this, there is a strong need for effective interventions that can decrease the high residual risk seen in patients with HF. Several device options exist that are approved by the US Food and Drug Administration and that have been shown to decrease morbidity and/or mortality in patients among whom GDMT is maximized. These …

Distinct Intrinsic And Extrinsic Factors Differentially Regulate Skeletal Stem Cells In Calvaria Versus Long Bones During Bone Regeneration, Jea Solidum, Kohei Yamasaki, Youngjae Jeong, Laura Ortinau, Francisco Heralde, Dongsu Park

Faculty, Staff and Students Publications

Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not been well elucidated. Here, using an inducible Prx1-CreER-EGFP+/−;Rosa26-tdTomato mouse model, we observed that endogenous Prx1+ Su-SSCs and their orthotopic transplantation into calvarial injury do not form cartilage intermediates at the injury sites, while the transplantation of Prx1+ LB-PSSCs into LB injury induces osteochondrogenic differentiation, respectively. However, the heterotopic transplantation of Prx1+ Su-SSCs (Su-SSCs …

A Novel Self-Inhaled Nicotine Exposure System In Murine Models Reveals Age-Dependent Metabolic Effects Of Nicotine, Xu Xu, Hailan Liu, Meng Yu, Qingzhuo Liu, Yongxiang Li, Yue Deng, Yuxue Yang, Jingjing Cheng, Yutian Liu, Mengjie Wang, Xing Fang, Longlong Tu, Olivia Z Ginnard, Kristine M Mcdermott, Darah Threat, Fuhui Wang, Meixin Sun, Xinming Liu, Jiamin Qiu, Xi Wu, Jinjing Jian, Tong Zhou, Megan E Burt, Sanika V Jossy, Junying Han, Chunmei Wang, Yongjie Yang, Yong Xu, Yuhan Shi

Faculty, Staff and Students Publications

Background: Nicotine is known to influence metabolism and body weight, yet existing murine models of nicotine exposure often fail to replicate human smoking behaviors accurately. To address this gap, we designed a cost-effective, self-administered nicotine inhalation system that allows mice to voluntarily inhale nicotine vapor generated from e-liquid.

Results: Using this system, we investigated the metabolic effects of nicotine exposure in adult and adolescent mice. Adult mice exposed to nicotine vapor for 10 days exhibited significant weight loss, which was rapidly regained upon cessation, paralleling human smoking patterns. In contrast, adolescent mice did not lose weight during nicotine exposure but …

Approach To Ophthalmic Surgery Involving The Anterior Vitreous: A Clinical Practice Update From The American Society Of Retina Specialists, Matthew R Starr, Christina Y Weng, Lejla Vajzovic, Kevin J Blinder, Judy E Kim, J Michael Jumper

Faculty, Staff and Students Publications

When encountering diseases of the anterior vitreous and peripheral retina (ie, the "middle segment" of the eye), vitreoretinal (VR) surgeons are specifically trained in surgical techniques for managing the vitreous and visualizing the peripheral retina during anterior vitrectomy, and therefore they are well equipped to address the complications of surgery involving the anterior vitreous space. This clinical update reviews and compares the current literature discussing techniques and patient outcomes related to complete pars plana vitrectomy versus incomplete, subtotal pars plana vitrectomy, and addresses the proposition of developing an abridged training curriculum for non-VR surgeons to acquire the knowledge and skills …

Synthesis, Structure-Activity Relationships, And Antitumor Activities Of Quinoxiline-Containing Inhibitors Of The Protein-Protein Interactions Between Transcription Coactivator Af9/Enl And Dot1l/Af4, Chandra Bhushan Mishra, Xin Li, Bala Krishna Moku, Sehun Kwak, Dnyaneshwar N Garad, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia (MLL) gene rearrangements cause ~75% of acute leukemia in infants and 5-10% in children and adults with poor clinical outcomes. Protein-protein interactions (PPI) between frequent MLL fusion partners AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Sixty-seven quinoxiline compounds were synthesized and tested for their ability to inhibit such PPIs. Compounds 16, 17, 59 and 63 were found to be potent inhibitors with IC50 values of 0.35-1.5 μM. Structure-activity relationships are discussed. Potent inhibitors can suppress expression of MLL target genes Myc and Meis1 and selectively block proliferation of MLL-r and …

Smarcal1 Is A New Osteosarcoma Predisposition Gene, Maryam Rafati, Lillian M Guenther, Laura E Egolf, D Matthew Gianferante, Jung Kim, Kevin Wang, Bin Zhu, Logan G Spector, Nathan Anderson, Katherine A Janeway, Donald A Barkauskas, Douglas S Hawkins, Ana Patiño-Garcia, Philip J Lupo, Michael E Scheurer, Lindsay Morton, Gregory T Armstrong, Yadav Sapkota, M Monica Gramatges, Massimo Serra, Claudia Hattinger, Katia Scotlandi, Irene L Andrulis, Jay S Wunder, Mandy L Ballinger, David M Thomas, Meredith Yeager, Michael Dean, Douglas R Stewart, Aurelie Vogt, Jia Liu, Belynda D Hicks, Wen-Yi Huang, Maria Teresa Landi, Adriana Lori, W Ryan Diver, Sharon A Savage, Stephen J Chanock, Lisa Mirabello

Faculty, Staff and Students Publications

Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most cases are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2,119 osteosarcoma cases, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across three osteosarcoma case sets (1.8%, n = 2,119) than in 2,625 comparably sequenced cancer-free controls (0.3%; P <  .001). Cases with SMARCAL1 pathogenic variants had significantly improved overall survival compared to cases without these variants (hazard ratio 0.36, 95% CI 0.14-0.96, P = .034). In the UK Biobank (469,557 exomes), there was a 33-fold increased risk of osteosarcoma in individuals with SMARCAL1 pathogenic variants. These results identify SMARCAL1 as a new osteosarcoma predisposition gene and thus warrant follow-up to identify the mechanisms by which SMARCAL1 contributes to the etiology of osteosarcoma.

Lysosomes Signal Through The Epigenome To Regulate Longevity Across Generations, Qinghao Zhang, Weiwei Dang, Meng C Wang

Faculty, Staff and Students Publications

The epigenome is sensitive to metabolic inputs and crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We find that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate-activated protein kinase (AMPK) or reduction of lysosomal mechanistic-target-of-rapamycin (mTOR) signaling increased expression of a histone H3.3 variant and increased its methylation on K79, leading to lifespan extension across multiple generations. This transgenerational pro-longevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase, and was recapitulated by …

The Impact Of Myopia On Regional Visual Field Loss And Progression In Glaucoma, Anagha Lokhande, Luo Song, Yueyin Pang, Yan Luo, Louis R. Pasquale, Sarah R. Wellik, Carlos G. De Moraes, Jonathan S. Myers, Mohammad Eslami, Tobias Elze, Lucy Q. Shen, Nazlee Zebardast, David S. Friedman, Michael V. Boland, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to investigate the impact of myopia on regional visual field (VF) loss and progression in glaucoma.

METHODS: We included 112,633 24-2 VFs; longitudinal analyses comprised patients with at least 5 reliable VFs over 4 years. The degree of myopia was measured by spherical equivalent (SE) extracted from VF testing. Linear and Cox regressions determined the impact of myopia on regional VF loss and progression, respectively. We calculated three VF progression outcomes: (1) mean deviation (MD) progression: MD slope < 0; (2) total deviation (TD) pointwise progression: at least 3 TD locations with TD slope ≤-1 decibels (dB)/year; (3) MD fast progression: MD slope ≤-1 dB/year (P value < 0.05). Longitudinal analyses were conducted for all subjects and with exclusion of patients with high myopia (SE ≤-6.00 diopters [D]).

RESULTS: More negative SE values were associated with worse TD values in the paracentral VF …

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

The Microenvironment Of Ocular Surface In Keratoconus: A Systematic Review, Sana Niazi, Farideh Doroodgar, Stephen Pflugfelder, Kia Bayat, Seyed-Farzad Mohammadi, Maedeh Mazloomi, Jorge L Alió Del Barrio, Majid Moshirfar, Jorge L Alió

Faculty, Staff and Students Publications

Purpose: Keratoconus is a progressive corneal ectatic disorder characterized by thinning and irregularity of the cornea, significantly impairing visual acuity. Recent studies have explored how non-ectatic conditions, such as dry eye and tear film instability and alteration of the ocular surface microenvironment, contribute to the development and progression of keratoconus. This comprehensive review aims to investigate the complex relationship between keratoconus and ocular surface diseases by examining the microenvironmental changes that occur on the ocular surface throughout the course of keratoconus, as well as the related clinical implications.

Methods: In this PROSPERO-registered study (ID: CRD42025643808), PubMed, Scopus, Cochrane, Embase, Web …

Lung Nr3c1+ And Cxcr6high T Cells Distinguish Immunopathogenesis Of Human Emphysema, Yun Zhang, Maor Sauler, David B Corry, Scott A Ochsner, Sarah Perusich, Li-Zhen Song, Joshua Malo, Raul San Jose Estepar, Francesca Polverino, Farrah Kheradmand

Faculty, Staff and Students Publications

There is a significant knowledge gap in how T cells promote emphysema in smokers with chronic obstructive pulmonary disease (COPD). Single-cell RNA sequencing (scRNA seq) analysis of human samples and relevant clinical data can provide new mechanistic insights into disease pathogenesis. We generated a human lung scRNA seq dataset with extensive disease characteristic annotation and analyzed a second independent scRNA seq dataset to examine the pathophysiological role of T cells in emphysema. Comparisons of pulmonary immune landscapes in emphysematous (E)-COPD, non-emphysematous (NE)-COPD, and control showed positive enrichment of T cells in E-COPD. Pathway analyses identified upregulated inflammatory states in CD4 …

Pediatric Heart Failure: A Practical Guide For Primary Care Providers Supporting Families Across The Care Continuum, Shahnawaz Amdani, Kriti Puri, Julie Glickstein, Joseph A Spinner, Jonathan N Johnson, Ashraf S Harahsheh, Majd Makhoul, Susan Denfield

Faculty, Staff and Students Publications

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF.

Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF.

Results: HF in children most commonly results from congenital heart disease and …

Adsl Deficiency Is A Secondary Mitochondrial Disease Affecting Organelle Homeostasis And Erk2/Akt Signaling In A Linear Genotype-Phenotype Relation, Matteo Bordi, Beatrice Testa, Claudia Compagnucci, Fiorella Colasuonno, Francesca Cipressa, Elisabetta Betterini, Andrea Mancini, Claudia Carsetti, Illari Salvatori, Caterina Ferraina, Ming Yang, Rossella De Cegli, Eugenio Del Prete, Chiara Veroni, Salvatore Rizza, Sofia Mauri, Elena Ziviani, Marina Macchiaiolo, Davide Vecchio, Filippo Maria Panfili, Teresa Rizza, Gerrit Weber, Rosalba Carrozzo, Alberto Ferri, Silvia Campello, Andrea Ballabio, Christian Frezza, Gianluca Cestra, Marco Tartaglia, Andrea Bartuli, Francesco Cecconi

Duncan NRI Faculty and Staff Publications

Adenylosuccinate lyase deficiency (ADSLd) is a rare autosomal recessive purine metabolism disorder with several clinical manifestations. While toxic substrate accumulation is a known hallmark, no additional molecular mechanisms have been established. Here, we show that ADSLd is associated with mitochondrial dysfunction, including increased fragmentation, impaired respiration, and reduced ATP production. The severity of mitochondrial impairment correlates with ADSLd pathology, especially in mitochondria-dependent tissues. We also identify defects in mitochondrial dynamics and transport linked to ERK2 and AKT suppression. Notably, overexpressing constitutively active ERK2 or supplementing purine intermediates partially rescues the mitochondrial phenotype. These findings suggest an alternative disease mechanism and …

Next-Gen Tools In Cancer Neuroscience, Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara Mcerlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair

Faculty, Staff and Student Publications

The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Deciphering The Mycn-Driven Metabolic Microenvironment Of Neuroblastoma, Amber Wolf, Davide Leardini, Lingzhi Li, Riccardo Masetti, Costas A Lyssiotis, Eveline Barbieri

Faculty, Staff and Students Publications

Oncogenic MYCN drives aggressive disease in many cancers including neuroblastoma (NB). Metabolic reprogramming is essential to support cancer cell homeostasis and survival under nutrient- and oxygen-deprived conditions. MYCN directly reprograms many nodes of tumor-intrinsic metabolism, which have significant repercussions on the cells of the tumor microenvironment (TME), resulting in complex intercellular metabolic circuits that contribute to the immunosuppressive microenvironment of NB. These metabolic circuits are also regulated by the organismal and cellular circadian clock and host diet to further impact the TME and NB oncogenesis. This review discusses the mechanisms by which MYCN regulates the metabolic crosstalk between tumor, TME, …

Understanding Cancer Survivorship Care Needs Using Amazon Reviews: Content Analysis, Algorithm Development, And Validation Study, Liwei Wang, Qiuhao Lu, Rui Li, Taylor B Harrison, Heling Jia, Ming Huang, Heidi Dowst, Rui Zhang, Hoda Badr, Jungwei W Fan, Hongfang Liu

Faculty, Staff and Students Publications

Background: Complementary therapies are being increasingly used by cancer survivors. As a channel for customers to share their feelings, outcomes, and perceived knowledge about the products purchased from e-commerce platforms, Amazon consumer reviews are a valuable real-world data source for understanding cancer survivorship care needs.

Objective: In this study, we aimed to highlight the potential of using Amazon consumer reviews as a novel source for identifying cancer survivorship care needs, particularly related to symptom self-management. Specifically, we present a publicly available, manually annotated corpus derived from Amazon reviews of health-related products and develop baseline natural language processing models using deep …

Sars-Cov-2 Nsp13 Interacts With Tead To Suppress Hippo-Yap Signaling, Fansen Meng, Jong Hwan Kim, Chang-Ru Tsai, Jeffrey D Steimle, Jun Wang, Yufeng Shi, Rich G Li, Bing Xie, Vaibhav Deshmukh, Shijie Liu, Xiao Li, James F Martin

Faculty, Staff and Students Publications

The Hippo pathway controls organ development, homeostasis, and regeneration primarily by modulating YAP/TEAD-mediated gene expression. Although emerging studies report Hippo-YAP dysfunction after viral infection, it is largely unknown in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we analyzed RNA sequencing data from human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and SARS-CoV-2-infected human lung samples, and observed a decrease in YAP target gene expression. In screening SARS-CoV-2 nonstructural proteins, we found that nonstructural protein 13 (NSP13), a conserved coronavirus helicase, inhibits YAP transcriptional activity independent of the upstream Hippo kinases LATS1/2. Consistently, introducing NSP13 into mouse cardiomyocytes suppresses …

Atrial Fibroblast-Derived Macrophage Migration Inhibitory Factor Promotes Atrial Macrophage Accumulation In Postoperative Atrial Fibrillation, Joshua A Keefe, Jose Alberto Navarro-Garcia, Shuai Zhao, Mihail G Chelu, Xander Ht Wehrens

Faculty, Staff and Students Publications

New study: Blocking MIF protein prevents irregular heartbeats after surgery by reducing harmful immune cell buildup in the atria.

Cerebellar Dysfunction In A Mouse Model Of Childhood-Onset Manganese-Induced Dystonia Parkinsonism, Alexander N Rodichkin, Amanda M Brown, Pavani Devabathini, Jennifer L Mcglothan, Si Chen, Ajith Pattammattel, Yong S Chu, Tao Lin, Daniel D Pontow, Karam Abilmouna, Ritishka Kapoor, Sarah E Hardin, Yulia Pushkar, Roy V Sillitoe, Tomás R Guilarte

Duncan NRI Faculty and Staff Publications

Humans with pathogenic variants of the manganese (Mn) transporter gene SLC39A14 exhibit highly elevated brain Mn concentrations and childhood-onset dystonia-parkinsonism. Here we show that Slc39a14-knockout (KO) mice, a preclinical model of the disease with elevated Mn concentrations in the CB, express deficits in physiological tremor implicating cerebellar (CB) dysfunction. Imaging of intracellular Mn in Purkinje cells (PCs) using synchrotron-based X-ray fluorescence microscopy confirmed highly elevated Mn concentrations in the PCs of Slc39a14-KO mice. To determine biological pathways altered in the CB of Slc39a14-KO mice relative to wildtype (WT), we performed RNA sequencing and discovered significant upregulation of pathways and genes …