Medicine and Health Sciences Commons^™

A Picture Puzzle Approach To Microbes, Infectious Diseases, History And Art, Adarsh Bhimraj

History of Medicine Seminar

Topics covered in this session:

• What is proper attire for doctors to wear?
• Why read history?
• Picture Puzzles

"I Just Really Felt Like I Was Heard For The First Time": Survivor Experiences With An Adult Forensic Interviewing Model, Morgan E Pettyjohn, Aly Kramer Jacobs, Khara Breeden, Bethany L Backes, Leila Wood

Faculty, Staff and Student Publications

Adult forensic interviewing (AFI) collects evidence for the investigation and prosecution of interpersonal violence in a trauma-informed setting. The present study uses mixed methods evaluation data from an AFI program in the U.S. to assess survivors' perceptions of safety and the utility of participating in these interviews. Most participants felt the process was beneficial to their personal lives and criminal justice system engagement by: (a) allowing them to share their stories in more detail, (b) supporting their healing journeys, and (c) helping them feel safer through resource referral. AFI is a promising practice that warrants continued research.

Robust Detection Of Watermarks For Large Language Models Under Human Edits, Xiang Li, Feng Ruan, Huiyuan Wang, Qi Long, Weijie J Su

Faculty, Staff and Student Publications

Watermarking has offered an effective approach to distinguishing text generated by large language models (LLMs) from human-written text. However, the pervasive presence of human edits on LLM-generated text dilutes watermark signals, thereby significantly degrading detection performance of existing methods. In this paper, by modeling human edits through mixture model detection, we introduce a new method in the form of a truncated goodness-of-fit test for detecting watermarked text under human edits, which we refer to as Tr-GoF. We prove that the Tr-GoF test achieves optimality in robust detection of the Gumbel-max watermark in a certain asymptotic regime of substantial text modifications …

Impacts Of The Conductive Networks On Solid-State Battery Operation, Shimao Deng, Yixian Wang, Tianxiao Sun, Wenlong Li, Mingyuan Ge, Jian Wang, Peter Cloetens, Piero Pianetta, David Mitlin, Yijin Liu

Faculty, Staff and Student Publications

The micromorphology of composite cathodes is known to play a vital role in determining all‐solid‐state battery (ASSB) performance. However, much of our current understanding is derived from empirical observations, lacking a deeper mechanistic foundation. The “rocking chair” concept of battery chemistry requires maintaining charge neutrality, emphasizing the necessity of examining electrode micromorphology from the perspective of conductive networks. This study systematically investigates the microscopic electrochemical impacts of conductive network micromorphology by varying the Li+‐to‐e− channel ratio in cathodes comprising LiNbO3‐coated LiNi0.8Co0.1Mn0.1O2, Li6PS5Cl, and carbon fibers. Utilizing multiscale synchrotron‐based spectro‐microscopy, we unravel that unbalanced Li+ and e− conducting channels intensify charge …

Anticonvulsant Use In Older Age Bipolar Disorder In A Global Sample From The Global Aging And Geriatric Experiments In Bipolar Disorder Project: Utilisation D'Anticonvulsivants Pour Le Traitement Des Troubles Bipolaires Du Sujet Âgé Auprès D'Un Échantillon Mondial Provenant Du Projet Gage-Bd, Katie C Bodenstein, Myriam Lesage, Paola Lavin, Sigfried Schouws, Melis Orhan, Alexandra Beunders, Osvaldo P Almeida, Kursat Altinbas, Vicent Balanzá-Martínez, Izabela G Barbosa, Hilary P Blumberg, Farren B S Briggs, Cynthia V Calkin, Orestes V Forlenza, Brent Forester, Ariel G Gildengers, Benno C M Haarman, Tomas Hajek, Beny Lafer, Paula V Nunes, Benoit Mulsant, Andrew T Olagunju, Regan E Patrick, Joquim Radua, Kaylee Sarna, Christian Simhandl, Jair C Soares, Ashley N Sutherland, Nicole Fiorelli, Antonio L Teixeira, Shangying Tsai, Eduard Vieta, Joy Yala, Lisa Eyler, Annemiek Dols, Martha Sajatovic, Soham Rej

Faculty, Staff and Student Publications

Background:

Anticonvulsants are an essential treatment for bipolar disorder; however, there is relatively little known about their use in older age bipolar disorder (OABD). In this paper, which leverages a large international dataset, we aim to 1) describe the use of anticonvulsants in OABD compared to younger age bipolar disorder (YABD; ages < 50 years old) and 2) explore any demographic/clinical correlates.

Methods:

A secondary analysis was conducted on the international data from the Global Aging and Geriatric Experiments in Bipolar Disorder project. The main objective was to report the prevalence of anticonvulsant use in OABD over 50 years old (mean age = 62.27) and the most prescribed anticonvulsant. Additional …

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 …

Benefit Of Icosapent Ethyl Across Types And Sizes Of Myocardial Infarction In Reduce-It, Chen Gurevitz, Deepak L Bhatt, Robert P Giugliano, Ph Gabriel Steg, Michael Miller, Eliot A Brinton, Terry A Jacobson, Steven B Ketchum, Armando Lira Pineda, Ralph T Doyle, Gabriella Giugliano, R Preston Mason, Jean-Claude Tardif, Fabrice M A C Martens, Christie M Ballantyne, Matthew J Budoff, C Michael Gibson

Faculty, Staff and Students Publications

Aims: We studied the efficacy and safety of icosapent ethyl (IPE) 4g daily in reducing the risk of myocardial infarction (MI) across different MI subtypes and sizes, among REDUCE-IT high-risk patients with hypertriglyceridemia.

Methods: REDUCE-IT was a phase 3b, double-blind multicenter trial. Patients with established CVD or diabetes who were treated with statins and had moderate hypertriglyceridemia were randomized to receive IPE 4g daily or placebo. The current analysis focused on MI subtypes (fatal MI, nonfatal MI, ST-segment elevation MI (STEMI), non-STEMI (NSTEMI)), as well as MI size (measured by multiples of troponin upper limit of normal) and MI-related complications. …

Repeat Selective Dorsal Rhizotomy For Residual Spasticity: Illustrative Case, Elizabeth Ledbetter, Aloysia L Schwabe, Heather Sgro, Sarah Slocum, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Selective dorsal rhizotomy (SDR) is typically a one-time surgical procedure supported by intense rehabilitation to improve ambulatory capability in children with spastic cerebral palsy (CP).

Observations: The authors present the unique case of a teenager with spastic diplegic CP who had undergone L2-S1 SDR as a child and presented with residual focal spasticity in the right plantar flexors. He underwent revision SDR at the right L5 and S1 levels in addition to decompression of canal stenosis. Postoperatively, he had notable improvement in his gait with relief of preoperative right knee and foot pain, improved ease of ambulation, and improved …

Bridging The Cost-Effectiveness Gap In Cardiovascular Disease Prevention For Statin-Intolerant Patients, Jerrin S Philip, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

An Open Trial For Transdiagnostic Behavior Therapy For Primary Care (Tbt-Pc) In Veterans With Symptoms Of Depression And Anxiety, Daniel F Gros, Stephanie Hart, Michelle Pompei, Ron Acierno

Faculty, Staff and Student Publications

Transdiagnostic psychotherapies were developed to address multiple diagnostic presentations via a single, easier-to-implement protocol. However, despite advances, these protocols are largely limited to longer formats designed for mental health settings. The present study investigated a version of Transdiagnostic Behavior Therapy (TBT-PC) that was adapted for primary care settings. Forty-one participants with emotional disorders received 6 sessions of TBT-PC, with symptoms of depression and anxiety assessed at baseline, immediate post-treatment, and at 3-month follow-up. Medium treatment effects for symptoms of depression and anxiety were evidenced at post-treatment and sustained at follow-up. Treatment feasibility was supported by excellent attendance, treatment completion, and …

Combined Annual Modulation Dark Matter Search With Cosine-100 And Anais-112, N Carlin, J Y Cho, J J Choi, S Choi, A C Ezeribe, L E França, C Ha, I S Hahn, S J Hollick, S B Hong, E J Jeon, H W Joo, W G Kang, M Kauer, B H Kim, H J Kim, J Kim, K W Kim, S H Kim, S K Kim, W K Kim, Y D Kim, Y H Kim, Y J Ko, D H Lee, E K Lee, H Lee, H S Lee, H Y Lee, I S Lee, J Lee, J Y Lee, M H Lee, S H Lee, S M Lee, Y J Lee, D S Leonard, N T Luan, V H A Machado, B B Manzato, R H Maruyama, R J Neal, S L Olsen, H K Park, H S Park, J C Park, J S Park, K S Park, K Park, S D Park, R L C Pitta, H Prihtiadi, S J Ra, C Rott, K A Shin, D F F S Cavalcante, M K Son, N J C Spooner, L T Truc, L Yang, G H Yu, J Amaré, J Apilluelo, S Cebrián, D Cintas, I Coarasa, E García, M Martínez, Y Ortigoza, A Ortiz De Solórzano, T Pardo, J Puimedón, M L Sarsa, C Seoane

Faculty and Staff Publications

The annual modulation signal, claimed to be consistent with dark matter as observed by DAMA/LIBRA in a sodium-iodide based detector, has persisted for over two decades. COSINE-100 and ANAIS-112 were designed to test the claim directly using the same target material. COSINE-100, located at Yangyang Underground Laboratory in South Korea, and ANAIS-112, located at Canfranc Underground Laboratory in Spain, have been taking data since 2016 and 2017, respectively. Each experiment published its respective results independently. In this Letter, we present the results of an annual modulation search as a test of the signal observed by DAMA/LIBRA with the first three …

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing

Epac1 Deletion Attenuates Müller Glial Pathological Activation And Mitigates Retinal Neurodegeneration In Ischemia-Induced Retinopathy, Shuizhen Shi, Fan Xia, Zhongqiao Lu, Erick Palacios, Fang Mei, Massoud Motamedi, Xiaodong Cheng, Hua Liu, Wenbo Zhang

The Brown Foundation: Institute of Molecular Medicine

Introduction: Ischemia-induced retinopathies, such as retinopathy of prematurity and proliferative diabetic retinopathy, are major causes of vision loss. Both pathological neovascularization and neuronal damage contribute to vision impairment in these conditions, yet current therapies primarily target neovascularization and may further compromise neuronal health.

Objectives: Cyclic AMP (cAMP) is a widely recognized second messenger regulating diverse physiological and pathological processes. Exchange protein directly activated by cAMP (Epac) is a recently identified effector of cAMP signaling. This study aimed to investigate the role of Epac1 in ischemia-induced retinopathy and elucidate its underlying mechanisms using a mouse model of oxygen-induced retinopathy (OIR).

Methods: …

Prenatal Metabolomics Analysis And Fetal Congenital Anomalies And Genetic Conditions: A Review Of Current Literature, Sarah Araji, Onur Turkoglu, Mohamad Ali Maktabi, Tracy Ashby, Ignatia B Van Den Veyver

Library Staff Publications

Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we …

Protocol For Non-Invasive Pulsed-Doppler Evaluation Of Blood Flow In The Mouse Ophthalmic Artery, Radwa Awad, Emil Martin, Anilkumar K Reddy, Iraida Sharina

Faculty, Staff and Student Publications

The number of reliable and non-invasive techniques to characterize ocular blood flow is limited. Here, we present a protocol for identifying a soft tissue window in the orbital aperture using pulsed-Doppler ultrasonography to offer real-time, non-invasive blood flow velocity monitoring in the mouse ophthalmic artery. We describe steps for preparing a mouse, positioning the ultrasound probe, and acquiring and recording signals. We then detail procedures for analyzing results using a workstation equipped with Doppler flow velocity software. For complete details on the use and execution of this protocol, please refer to Sharina et al.

Metabolic Shifts In Murine Inner Ears Mimicking Erythrocytes And Plasma Reveal Diagnostics And Early Predictors For Age-Related Hearing Loss, Qi Guo, Zhenjiang Li, Cheng Luo, Changhan Chen, Xi Long, Yidan Wang, Qingfen Qiang, Fang Yu, Wuping Liu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Age-related hearing loss (ARHL) is a major public health concern, driven by the interplay of multiple factors. Here, we reveal spatiotemporal metabolic shifts in murine inner ears mirroring erythrocytes and plasma. Isotope-labeled glucose tracing demonstrates a metabolic rerouting favoring glycolysis over the pentose phosphate pathway, alongside downregulation of the tricarboxylic acid cycle, indicating impaired energy production and redox homeostasis. Accumulation of medium- and long-chain acylcarnitines further exacerbates lipotoxicity. Notably, age-dependent depletion of arginine, lysine, proline, and glycine disrupts the arginine-polyamine-urea cycle. Translationally, UK Biobank plasma metabolomics links omega-6 fatty acids, linoleic acid, glycine, and albumin to ARHL resilience, while branched-chain …

Blue-Shifted Ancyromonad Channelrhodopsins For Multiplex Optogenetics, Elena G Govorunova, Oleg A Sineshchekov, Hai Li, Yueyang Gou, Hongmei Chen, Shuyuan Yang, Yumei Wang, Stephen Mitchell, Alyssa Palmateer, Leonid S Brown, François St-Pierre, Mingshan Xue, John L Spudich

Duncan NRI Faculty and Staff Publications

Light-gated ion channels from protists (channelrhodopsins or ChRs) are optogenetic tools widely used for controlling neurons and cardiomyocytes. Multiplex optogenetic applications require spectrally separated molecules, which are difficult to engineer without disrupting channel function. Scanning numerous sequence databases, we identified three naturally blue-shifted ChRs from ancyromonads. They form a separate branch on the phylogenetic tree and contain residue motifs characteristic of anion ChRs (ACRs). However, only two conduct chloride, whereas the closely related Nutomonas longa homolog generates inward cation currents in mammalian cells under physiological conditions, significantly exceeding those by previously known tools with similar spectral maxima (peak absorption at …

Gait Analysis In Rett Syndrome: Integrating Linear And Nonlinear Techniques, Dacia Martinez Diaz, Brock Futrell, Bernhard Suter, Charles S Layne

Faculty, Staff and Students Publications

Rett syndrome is a rare neurodevelopmental disorder that significantly impairs bipedal postural control and walking ability. This study quantifies the gait characteristics of 22 females with Rett syndrome (divided into 3 age groups) and compares them with age-matched neurotypical females. Bilateral sagittal plane joint angles of the hip, knee, and ankle were analyzed. Measures included joint range of motion, stride time, peak angular velocity, angle-angle diagrams, phase portrait areas, and asymmetries. Results revealed reduced joint range of motion and angular velocity in individuals with Rett syndrome, as well as greater asymmetries in gait parameters reflecting disruptions in bilateral coordination. Phase …

Can Handoffs Bridge The Interprofessional Divide To Build A Team?, Aubrey Samost-Williams, Eric J Thomas

Faculty, Staff and Student Publications

No abstract provided.

Cetuximab Increases Lgr5 Expression And Augments Lgr5-Targeting Antibody-Drug Conjugate Efficacy In Patient-Derived Colorectal Cancer Models, Peyton C High, Zhengdong Liang, Cara Guernsey-Biddle, Shraddha Subramanian, Yueh-Ming Shyu, Adela M Aldana, Yukimatsu Toh, Kendra S Carmon

The Brown Foundation: Institute of Molecular Medicine

Colorectal cancer (CRC) remains the second-leading cause of cancer-associated deaths, indicating an urgent need for improved therapeutic options. We previously generated antibody-drug conjugates (ADCs) targeting the cancer stem-like cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5). However, tumor relapse due to LGR5 downregulation and suboptimal payload selection warrants strategies to improve ADC efficacy. Here, we report that cetuximab, an epidermal growth factor receptor (EGFR)-targeting monoclonal antibody indicated for RASWT metastatic CRC, augments LGR5 expression independent of RAS/PIK3CA mutation status and promotes EGFR-LGR5 interactions. Furthermore, we describe the development of LGR5 ADCs incorporating a camptothecin-derived payload that is well tolerated …

Connecting Innovation And Trust Through Translational Sciences – A Need For A Community Focus And Effective Education Strategiess, Filipa Godoy-Vitorino, Michelle Borrero, Josué Pérez-Santiago, Rubén García-García, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Report of a conference held in Puerto Rico, this article highlights how interdisciplinary translational science-anchored in education, public trust, and equity-can accelerate innovation in cancer therapy while empowering underserved communities through inclusive training, collaboration, and research participation.

Disparities In Liver Transplantation For Metabolic Dysfunction-Associated Steatohepatitis-Associated Hepatocellular Carcinoma, David W Victor, Sudha Kodali, Mazen Noureddin, Elizabeth W Brombosz, Analisa Lopez, Tamneet Basra, Edward A Graviss, Duc T Nguyen, Ashish Saharia, Ashton A Connor, Maen Abdelrahim, Yee Lee Cheah, Caroline J Simon, Mark J Hobeika, Constance M Mobley, R Mark Ghobrial

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly common, as is hepatocellular carcinoma (HCC) in the background of MASH. Liver transplantation (LT) provides superior long-term survival for patients with unresectable MASH-HCC, but not all patients have equal access to transplant. MASH-HCC disproportionately affects Hispanic patients, but minorities are less likely to undergo LT for HCC. Additionally, females also undergo LT at lower rates than males.

Aim: To investigate whether race/ethnicity and sex affect LT waitlist outcomes.

Methods: Records of adults with MASH-HCC in the United States Organ Procurement and Transplantation Network database listed for LT between 1/2015 and 12/2021 were analyzed. …

Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated With Olfactory Dysfunction, Mohammed Aslam Imtiaz, Konstantinos Melas, Adrienne Tin, Valentina Talevi, Honglei Chen, Myriam Fornage, Srishti Shrestha, Martin Gögele, David Emmert, Cristian Pattaro, Peter Pramstaller, Franz Förster, Katrin Horn, Thomas H Mosley, Christian Fuchsberger, Markus Scholz, Monique M B Breteler, N Ahmad Aziz

Faculty, Staff and Student Publications

Background: Olfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown. Therefore, here we aimed to elucidate its genetic architecture through a genome-wide association study meta-analysis (GWMA).

Methods: This GWMA included the participants of European ancestry (N = 22,730) enrolled in four different large population-based studies followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). Olfactory dysfunction was assessed using a 12-item smell identification test.

Results: GWMA revealed a novel genome-wide significant locus (tagged by single nucleotide …

Structural Basis For Mtorc1 Activation On The Lysosomal Membrane, Zhicheng Cui, Alessandra Esposito, Gennaro Napolitano, Andrea Ballabio, James H Hurley

Duncan NRI Faculty and Staff Publications

The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth factor (GF) and nutrient signals to stimulate anabolic processes connected to cell growth and inhibit catabolic processes such as autophagy1,2. GF signalling through the tuberous sclerosis complex regulates the lysosomally localized small GTPase RAS homologue enriched in brain (RHEB)3. Direct binding of RHEB-GTP to the mTOR kinase subunit of mTORC1 allosterically activates the kinase by inducing a large-scale conformational change4. Here we reconstituted mTORC1 activation on membranes by RHEB, RAGs and Ragulator. Cryo-electron microscopy showed that RAPTOR and mTOR interact directly with the membrane. Full engagement of the membrane anchors …

Galntl5 Binds Galnac And Is Required For Migration Through The Uterotubal Junction And Sperm-Zona Pellucida Binding, Taichi Noda, Reika Uriu, Daisuke Mashiko, Hina Shinohara, Yongcun Qu, Ayumu Taira, Ryan M Matzuk, Duri Tahala, Motochika Nakano, Kimi Araki, Zhifeng Yu, Ying Zhang, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Objective: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston.

Methods: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times.

Results: A total of 32,640 stroke admissions from 29 studies …

Galntl5 Binds Galnac And Is Required For Migration Through The Uterotubal Junction And Sperm-Zona Pellucida Binding, Taichi Noda, Reika Uriu, Daisuke Mashiko, Hina Shinohara, Yongcun Qu, Ayumu Taira, Ryan M Matzuk, Duri Tahala, Motochika Nakano, Kimi Araki, Zhifeng Yu, Ying Zhang, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 20 genes expressed in the male reproductive tract have been identified as essential factors for sperm migration to and through the utero-tubal junction (UTJ), and they are divided into ADAM3-dependent and ADAM3-independent pathways. In parallel, sperm having UTJ migration defects also show impaired binding to the zona pellucida (ZP). Herein, we demonstrate that knockout of Galntl5, encoding a sperm surface protein, causes impaired sperm binding with the UTJ and ZP, and null males have severe infertility. GALNTL5 appreciably disappears in sperm lacking Adam3 or Lypd4, required for ADAM3-dependent and ADAM3-independent pathways, and GALNTL5 binds to N …

Retraction Of Activation Of Rac1 By Src-Dependent Phosphorylation Of Dock180y1811 Mediates Pdgfrα-Stimulated Glioma Tumorigenesis In Mice And Humans, Haizhong Feng, Bo Hu, Kun-Wei Liu, Yanxin Li, Xinghua Lu, Tao Cheng, Jia-Jean Yiin, Songjian Lu, Susan Keezer, Tim Fenton, Frank B Furnari, Ronald L Hamilton, Kristiina Vuori, Jann N Sarkaria, Motoo Nagane, Ryo Nishikawa, Webster K Cavenee, Shi-Yuan Cheng

Faculty, Staff and Student Publications

No abstract provided.

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J Purwin, Casey D Stefanski, Renaira Oliveira Da Silva, Mitchell E Fane, Yash Chhabra, Jelan I Haj, Jessica Lf Teh, Rama Kadamb, Weijia Cai, Sheera R Rosenbaum, Vivian Chua, Nir Hacohen, Michael A Davies, Jessie Villanueva, Inna Chervoneva, Ashani T Weeraratna, Dan A Erkes, Claudia Capparelli, Julio A Aguirre-Ghiso, Andrew E Aplin

Faculty, Staff and Student Publications

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

33 Unresolved Questions In Nanoscience And Nanotechnology, Chad A Mirkin, Sarah Hurst Petrosko, Natalie Artzi, Koray Aydin, Austin Biaggne, C Jeffrey Brinker, Katherine E Bujold, Y Charles Cao, Rachel R Chan, Chaojian Chen, Peng-Cheng Chen, Xiaodong Chen, Olivier J G L Chevalier, Chung Hang Jonathan Choi, Richard M Crooks, Vinayak P Dravid, Jingshan S Du, Sasha B Ebrahimi, Hongyou Fan, Omar K Farha, C Adrian Figg, Tanner D Fink, Connor M Forsyth, Harald Fuchs, Franz M Geiger, Nathan C Gianneschi, Kyle J Gibson, David S Ginger, Sishi Guo, Justin S Hanes, Liangliang Hao, Jin Huang, Bryan M Hunter, Fengwei Huo, Jeongmin Hwang, Rongchao Jin, Shana O Kelley, Thomas J Kempa, Youngeun Kim, Sergej Kudruk, Sneha Kumari, Kaitlin M Landy, Ki-Bum Lee, Noel J Leon, Jun Li, Yuanwei Li, Zhiwei Li, Bin Liu, Guoliang Liu, Xiaogang Liu, Luis M Liz-Marzán, Jochen H Lorch, Taokun Luo, Robert J Macfarlane, Jill E Millstone, Milan Mrksich, Catherine J Murphy, Rajesh R Naik, Andre E Nel, Christopher Oetheimer, Jenny K Hedlund Orbeck, So-Jung Park, Benjamin E Partridge, Nicholas A Peppas, Michelle L Personick, Arindam Raj, Namrata Ramani, Michael B Ross, Stacey Barnaby Ross, Edward H Sargent, Tanushri Sengupta, George C Schatz, Dwight S Seferos, Tamar Seideman, Soyoung Eileen Seo, Bo Shen, Wooyoung Shim, Donghoon Shin, Ulrich Simon, Andrew J Sinegra, Peter T Smith, Alexander M Spokoyny, Peter J Stang, Alexander H Stegh, J Fraser Stoddart, Dayne F Swearer, Weihong Tan, Michelle H Teplensky, C Shad Thaxton, David R Walt, Mary X Wang, Zhe Wang, Wei David Wei, Paul S Weiss, Peter H Winegar, Younan Xia, Yi Xie, Xiaoyang Xu, Peidong Yang, Yiming Yang, Zihao Ye, Kuk Ro Yoon, Cuizheng Zhang, Hua Zhang, Ke Zhang, Liangfang Zhang, Xiaoyu Zhang, Ye Zhang, Zijian Zheng, Wenjie Zhou, Shengshuang Zhu, Wei Zhu

Faculty, Staff and Student Publications

Significant advances in science and engineering often emerge at the intersections of disciplines. Nanoscience and nanotechnology are inherently interdisciplinary, uniting researchers from chemistry, physics, biology, medicine, materials science, and engineering. This convergence has fostered novel ways of thinking and enabled the development of materials, tools, and technologies that have transformed both basic and applied research, as well as how we address critical societal challenges. In this Nano Focus, we pose and explore 33 questions whose answers could profoundly impact fields such as energy, electronics, the environment, optics, and medicine. These questions highlight the need for deeper foundational understanding, improved tools …

Sorting Nexin 3 Promotes Ischemic Retinopathy Through Rip1- And Rip3-Mediated Myeloid Cell Necroptosis And Mitochondrial Fission, Jiaojiao Wang, Chunhong Zhou, Kai Zhuang, Jiami Zou, Wanlu Qiu, Mei Jin, Weile Ye, Pinglian Yang, Zhihua Zheng, Qing Zhou, Zunnan Huang, Yuanxiang Wang, Peiqing Liu, Jing Lu, Yuqing Huo, Zhiping Liu

Faculty, Staff and Students Publications

Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell–mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts. Myeloid cell-specific deficiency …