Digital Commons Network^™

Signaling By Intracellular Β2-Adrenergic Receptors Regulates Ampa Receptor Trafficking And Synaptic Plasticity, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 …

Ifit3 Activation Significantly Contributes To Hiv-1-Associated Neurodegenerative Disorder-Mediated Neuroinflammation, Ranjit Kumar Das, Nirakar Sahoo, Deepa Roy, Chun Xu, Jose Galarza, Maria Camila Mejia Garza, Hansapani Rodrigo, Asim K. Duttaroy, Upal Roy

Health & Biomedical Sciences Faculty Publications

Introduction: The advent of effective combination antiretroviral therapy (cART) has significantly improved HIV-1 treatment, saving millions of lives. However, HAND remains a concern, particularly among aging individuals with HIV-1. The mechanisms underlying HAND are not well understood.

Methods: This study investigated the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and its upstream regulator, signal transducer, and activator of transcription 1 (STAT1), in HAND pathology. Using the SH-SY5Y neuroblastoma cell line and HIV-infected humanized mice, we examined the effects of the cART drugs, HIV Tat protein, and HIV-1 virus on STAT1 and IFIT3 expression.

Results: The results showed that …

Suppression Of Cardiac Allograft Vasculopathy By A Macrophage Efferocytosis Receptor, Sahil Shah, Aparnaa Ananthakrishnan, Matthew Deberge, Kristofor Glinton, Rebecca T L Jones, Mallory Filipp, Ivana Shen, Joey Lockhart, Connor W Lantz, Edward B Thorp

Faculty, Staff and Student Publications

Cardiac allograft vasculopathy remains a major cause of late morbidity following heart transplantation. While accumulating evidence implicates innate macrophages in the inflammatory progression of CAV, the underlying mechanisms remain incompletely understood. In murine models of CAV, we identified proteolytic cleavage of MERTK, a key anti-inflammatory receptor on macrophages, as a contributing factor to CAV progression. In a model of CAV, MERTK deficiency accelerated allograft rejection and increased intimal leukocyte infiltration. In contrast, mice expressing a genetically cleavage-resistant form of MERTK (MertkCR/CR) exhibited prolonged graft survival, reduced intimal thickening, diminished immune cell infiltration, and decreased circulating effector T cells. …

The Role Of Recruited Adipose Stromal Cells And Their Fibroblastic Differentiation In Cancer, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Faculty, Staff and Student Publications

Adipose stromal cells (ASCs) are perivascular mesenchymal progenitors of adipose tissue. In cancer patients, ASCs can mobilize and migrate to the tumor, where they subsequently play an important role in cancer progression. This biological process involves the conversion of recruited ASCs into cancer-associated fibroblasts (CAFs). ASC-derived CAFs influence the tumor microenvironment through extracellular matrix remodeling, vascularization, and immunomodulation. These and other processes mediated by secreted paracrine factors also affect gene expression in carcinoma cells to promote the epithelial-mesenchymal transition (EMT), metabolic adaptation, survival, and invasiveness of cancer cells. ASC-derived CAFs can enhance tumor aggressiveness, accounting in part for the link …

Computer-Aided Reading Of Chest Radiographs For Paediatric Tuberculosis: Current Status And Future Directions, Mackenzie Dupont, Robert Castro, Sandra V Kik, Megan Palmer, James A Seddon, Devan Jaganath

Faculty, Staff and Students Publications

Computer-aided detection (CAD) systems for automated reading of chest x-rays (CXRs) have been developed and approved for tuberculosis triage in adults but not in children. However, CXR is frequently the only adjunctive tool for clinical assessment in the evaluation of paediatric tuberculosis in primary care settings, and children would benefit from CAD models that can detect their unique clinical and radiographic features. To advance CAD for childhood tuberculosis, large, diverse paediatric CXR datasets linked to standardised tuberculosis classifications are required. These datasets would be used to train and validate paediatric-specific models for tuberculosis screening, diagnosis, and severity stratification. Previous studies …

Cathartocytosis: Jettisoning Of Cellular Material During Reprogramming Of Differentiated Cells, Jeffrey W Brown, Xiaobo Lin, Gabriel Anthony Nicolazzi, Xuemei Liu, Thanh Nguyen, Megan D Radyk, Joseph Burclaff, Jason C Mills

Faculty, Staff and Students Publications

Injury causes differentiated cells to undergo massive reprogramming to become proliferative and repair tissue via paligenosis. Gastric chief cells use paligenosis to reprogram into progenitor-like spasmolytic-polypeptide-expressing metaplasia (SPEM) cells. Stage 1 of paligenosis is the downscaling of mature cell architecture via a process involving lysosomes. Here, we notice that sulfated glycoproteins are not only digested during paligenosis but also excreted into the gland. Various genetic and pharmacological approaches show that endoplasmic reticulum membranes and secretory granule cargo are also excreted and that the process proceeds in parallel with but is mechanistically independent of autophagy. Three-dimensional light and electron microscopy demonstrated …

High-Speed Voltage Imaging Of Action Potentials In Molecular Layer Interneurons Reveals Sensory-Driven Synchrony That Augments Movement, Spencer T Brown, Meghana R Holla, Michelle A Land, Shuyuan Yang, Alex J Mcdonald, François St-Pierre, Indira M Raman

Faculty, Staff and Students Publications

Testing whether the synchrony of action potential firing is a cerebellar coding mechanism requires simultaneous recording, with high temporal fidelity, from populations of identified neurons. Here, we used targeted one-photon voltage imaging at 2–4 kHz to record action potentials from groups of ~10–300 molecular layer interneurons (MLIs) expressing a positively tuned, genetically encoded voltage indicator, FORCE1f or pAce. In awake resting mice, crus I MLIs fired brief (~1-ms) spikes at 20–60 spikes/s. Sensory stimuli of air puffs to the whiskers evoked short-latency (< 10 ms) increases in spiking probability. In most trials, >50% of MLIs fired synchronously with 4-ms temporal precision. The magnitude of puff-evoked whisks correlated tightly with …

Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations And Macrophage-Driven Metastasis In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Weiguo Wu, Brooks Scull, Angela M Major, Weidong Jin, Justin M M Cates, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a type of bone cancer that mostly affects kids and teens. The biggest danger is when the cancer spreads to the lungs, and current treatments do not work well for those cases. Immunotherapy, which helps the body’s immune system fight cancer, has worked for other cancers but is limited for osteosarcoma because we do not fully understand the environment around the tumor. Our research looked at various cells around the tumor to study why patients have worse outcomes. We found that certain cells, called M2 macrophages (M2) and myeloid-derived suppressor cells (MDSC), which weaken the immune system, are …

Pfkfb3 Activates Cad To Enhance De Novo Pyrimidine Synthesis For Cell Growth, Qingen Da, Yongfeng Cai, Qian Ma, Qiuhua Yang, Yapeng Cao, Yaqi Zhou, Dingwei Zhao, Zhiping Liu, Jiean Xu, Junming Quan, Liang Zhang, Rui Wang, Xuejun Jiang, Xiao Liu, Kunfu Ouyang, Zhen Han, Jikui Liu, Tao Wang, Chunxiang Zhang, Neal L Weintraub, David J R Fulton, Jun Zhao, Mei Hong, Zigang Li, Yuqing Huo

Faculty, Staff and Students Publications

Aerobic glycolysis, termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. Research on the direct interactions between glycolysis and other metabolic pathways is an emerging field that has garnered significant interest. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three …

Genome Sequence Of Lacticaseibacillus Paracasei G277-1.1, A Clinical Strain That Forms Enhanced Biofilms With Streptococcus Mutans, Xiaochang Huang, Hemendra Pal Dhaked, Yihong Li, Zezhang T. Wen

School of Dentistry Faculty Publications

Lacticaseibacillus paracasei G277-1.1 was isolated from dental plaque of a patient with severe early childhood caries. It forms synergistic biofilms with Streptococcus mutans in vitro. Here, we report its high-quality genome sequence, revealing insights on its inter-species interaction with S. mutans.

Intouch Week Of August 25, 2025, New York Medical College

InTouch

• Enhancing Campus Operations
• Celebrating NYMC and Metropolitan Hospital
• New Speech-Language Pathology Students Begin Their Academic Journey
• Historical Hahnemann Hospital Clock Adorns Sunshine Cottage Lobby
• Psoriasis and Cardiovascular Disease Link Not Clearly Recognized by Patients
• Student Spotlight: SOM Student Helps Develop Innovative Anesthesia App for WMC Residents

Mri-Guided Focused Ultrasound Thalamotomy For Neuropathic Pain In An Adolescent With Cranial Metastases: Illustrative Case, Sarah G Van Winkle, Danika L Paulo, Ashwin Viswanathan, Daniel Curry, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Neuropathic cancer pain (NCP) is a debilitating condition that is often refractory to conventional medical management. MRI-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) is an incisionless neurosurgical option for neuropathic pain palliation, but its use in pediatric patients and those with cranial metastases, a relative contraindication to MRgFUS, remains largely unexamined.

Observations: A 16-year-old male with metastatic rhabdomyosarcoma (RMS) with numerous cranial metastases experienced severe, diffuse, refractory NCP. The patient underwent bilateral CLT with MRgFUS. After the procedure, the patient experienced complete and durable resolution of his neuropathic pain. He only reported occasional somatic pain at sites of …

Astrocytes Expressing Mutant Hnrnpa1 Induce Non-Cell-Autonomous Motor Neuron Death, Qinxue Wu, Xionghao Liu, Tingting Zhang, Shiquan Cui, Bo Huang, Cao Huang, Qilin Cao, Xu-Gang Xia, Hongxia Zhou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pathogenic mutation of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is causative to amyotrophic lateral sclerosis (ALS). Neuron death resulting from pathogenic hnRNPA1 may not require its presence across all pertinent cells types, including neurons, glia, and muscles. Rather, the exclusive presence of pathogenic hnRNPA1 in a specific cell type, such as astrocytes, may suffice to substantially alter cellular functions. Consequently, this alteration initiates abnormal interaction within intricate neuron-glia networks, culminating in non-cell-autonomous motor neuron death. To investigate the pivotal role of non-cell-autonomous neuron death in hnRNPA1-associated ALS, we developed transgenic rats overexpressing mutant hnRNPA1 in specifically astrocytes. The confined overexpression of …

Predicting Regional Cerebral Blood Flow Using Voxel-Wise Resting-State Functional Mri, Hongjie Ke, Bhim M Adhikari, Yezhi Pan, David B Keator, Daniel Amen, Si Gao, Yizhou Ma, Paul M Thompson, Neda Jahanshad, Jessica A Turner, Theo G M Van Erp, Mohammed R Milad, Jair C Soares, Vince D Calhoun, Juergen Dukart, L Elliot Hong, Tianzhou Ma, Peter Kochunov

Faculty, Staff and Student Publications

Background: Regional cerebral blood flow (rCBF) is a putative biomarker for neuropsychiatric disorders, including major depressive disorder (MDD).

Methods: Here, we show that rCBF can be predicted from resting-state functional MRI (rsfMRI) at the voxel level while correcting for partial volume averaging (PVA) artifacts. Cortical patterns of MDD-related CBF differences decoded from rsfMRI using a PVA-corrected approach showed excellent agreement with CBF measured using single-photon emission computed tomography (SPECT) and arterial spin labeling (ASL). A support vector machine algorithm was trained to decode cortical voxel-wise CBF from temporal and power-spectral features of voxel-level rsfMRI time series while accounting for PVA. …

Prolonged Exposure To Food Odors Suppresses Feeding Via An Olfactory Bulb-To-Hypothalamus Circuit, Yao Liu, Hailan Liu, Huey-Xian Kelly Wong, Niccole Auld, Kristine M Conde, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z Ginnard, Yuxue Yang, Longlong Tu, Hesong Liu, Jonathan C Bean, Junying Han, Megan E Burt, Sanika V Jossy, Yongjie Yang, Chunmei Wang, Qingchun Tong, Benjamin R Arenkiel, Hongjie Li, Yong Xu, Yang He

The Brown Foundation: Institute of Molecular Medicine

Olfactory perception of food odors is a key determinant of eating behavior, including triggering appetite, facilitating food seeking and influencing food choice. While transient food-related olfactory cues stimulate appetite and provoke cravings in states of hunger, emerging evidence implies that prolonged and sustained exposure to food-derived odor (FO) suppresses feeding. However, the mechanisms by which olfaction induces hypophagia remain elusive. In this study, we show that prolonged FO exposure significantly suppresses food intake in male mice. We identified a subset of neurons in the ventral subiculum (vSub) that are specifically activated by FO. We further discovered that these FO-activated neurons …

Placental Polycyclic Aromatic Hydrocarbon (Pah) Levels Are Associated With Spontaneous Preterm Birth, Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D Shope, Joseph Hagan, Kjersti M Aagaard, Bhagavatula Moorthy, Melissa A Suter

Faculty, Staff and Students Publications

While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from …

Review Of Human Papillomavirus Vaccination Programs In United States Schools, Cassandra Duran, Aditi Gupta, Lynda Aririguzo, Norma Castillo, Sanghamitra M Misra

Faculty, Staff and Students Publications

Background: School vaccination programs (school-based and school-located) that include the human papillomavirus (HPV) vaccine have been implemented throughout the United States since 2009.

Methods: We conducted a review of school HPV vaccination programs in PUBMED, Google Scholar, Web of Science, Ovid, Medline, and Embase and included peer-reviewed studies originating in the United States that focused on any aspect of HPV school vaccination programs.

Results: Our review yielded 47 articles that fell into several categories: (1) parent and child perceptions, (2) school nurse perceptions, (3) development, (4) implementation, (5) outcomes, and (6) barriers and facilitators of HPV vaccination programs in schools. …

Targeting Sting To Disrupt Macrophage-Mediated Adhesion In Encapsulating Peritoneal Sclerosis, Juan Sun, Yuxiang Sun, Dandan Guo, Huolin Ye, Qiang Huang, Hu Zhou, Canming Li, Mei Liao, Yujia You, Hongli Shang, Pan Zhou, Dongxuan Wu, Janusz Witowski, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Encapsulating peritoneal sclerosis (EPS) is a life-threatening fibrotic condition characterized by severe abdominal adhesions, chronic inflammation, and significant morbidity. The lack of effective treatments for EPS stems from a limited understanding of its underlying mechanisms. In this study, we developed a modified mouse model of PD-induced EPS and investigated the role of the STING signaling pathway in disease progression. Our findings reveal that STING activation in peritoneal mesothelial cells significantly increases the secretion of the macrophage chemokine CCL2, leading to enhanced macrophage infiltration and the formation of pathological adhesions. Notably, pharmacological inhibition of STING using the inhibitor H151 effectively reduced …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Caf-Macrophage Crosstalk Fuels Immunotherapy Resistance, Yang Liu, Linghua Wang

Faculty, Staff and Student Publications

No abstract provided.

Prefrontal Cortex Astrocytes Modulate Distinct Neuronal Populations To Control Anxiety-Like Behavior, Eunyoung Kim, Hairuo Du, Yanqi Tan, Brandon L Brown, Yaowen Chang, Blanca Díaz-Castro, Jonathan V Sweedler, Xinzhu Yu

Faculty, Staff and Student Publications

Accumulating evidence has supported diverse regulatory functions of astrocytes in different neural circuits as well as various aspects of complex behaviors. However, little is known about how astrocytes regulate different neuronal subpopulations that are linked to specific behavioral aspects within a single brain region. Here, we show that astrocytes in the medial prefrontal cortex (mPFC) encode anxiogenic environmental cues in freely behaving mice. Silencing mPFC astrocyte Ca

Phase 1/2 Trial Of Encorafenib, Cetuximab, And Nivolumab In Microsatellite Stable Brafv600e Metastatic Colorectal Cancer, Van K Morris, Christine M Parseghian, Vahid Bahrambeigi, Nourhan Abdelfattah, Lianchun Xiao, Anjali Agrawal, Kangyu Lin, Kanwal P S Raghav, Robert A Wolff, Arvind Dasari, Ryan W Huey, Bryan K Kee, Michael J Overman, Jason A Willis, Phat H Le, Michelle Escano, Yunyu C Baig, Kelsey Pan, David Menter, Alda L Tam, Wai C Foo, Li Shen, Hey Min Lee, Thomas D Gallup, Cori Margain, Dave Gallup, Kimal I Rajapakshe, Paola A Guerrero, Jing Wang, Ryan B Corcoran, Anirban Maitra, Kyuson Yun, Scott Kopetz

Faculty, Staff and Student Publications

The BRAF inhibitor encorafenib and anti-epidermal growth factor receptor (EGFR) antibody cetuximab modestly improve survival for patients with microsatellite stable (MSS) BRAFV600E metastatic colorectal cancer (mCRC), characterized by higher immune activation than MSS BRAFwild-type colorectal cancer (CRC). In this phase 1/2 study (NCT04017650) of 26 participants with MSS BRAFV600E mCRC who received encorafenib, cetuximab, and anti-PD-1 antibody nivolumab, we report an overall response rate of 50% (95% confidence interval [CI] 29–71) and median progression-free survival of 7.4 months (95% CI, 5.6–9.6). Transcriptomic profiling of pretreatment biopsies and extracellular vesicle RNA (evRNA) isolated from plasma show …

Human Interpretable Grammar Encodes Multicellular Systems Biology Models To Democratize Virtual Cell Laboratories, Jeanette A I Johnson, Daniel R Bergman, Heber L Rocha, David L Zhou, Eric Cramer, Ian C Mclean, Yoseph W Dance, Max Booth, Zachary Nicholas, Tamara Lopez-Vidal, Atul Deshpande, Randy Heiland, Elmar Bucher, Fatemeh Shojaeian, Matthew Dunworth, André Forjaz, Michael Getz, Inês Godet, Furkan Kurtoglu, Melissa Lyman, John Metzcar, Jacob T Mitchell, Andrew Raddatz, Jacobo Solorzano, Aneequa Sundus, Yafei Wang, David G Denardo, Andrew J Ewald, Daniele M Gilkes, Luciane T Kagohara, Ashley L Kiemen, Elizabeth D Thompson, Denis Wirtz, Laura D Wood, Pei-Hsun Wu, Neeha Zaidi, Lei Zheng, Jacquelyn W Zimmerman, Jude M Phillip, Elizabeth M Jaffee, Joe W Gray, Lisa M Coussens, Young Hwan Chang, Laura M Heiser, Genevieve L Stein-O'Brien, Elana J Fertig, Paul Macklin

Faculty, Staff and Student Publications

Cells interact as dynamically evolving ecosystems. While recent single-cell and spatial multi-omics technologies quantify individual cell characteristics, predicting their evolution requires mathematical modeling. We propose a conceptual framework-a cell behavior hypothesis grammar-that uses natural language statements (cell rules) to create mathematical models. This enables systematic integration of biological knowledge and multi-omics data to generate in silico models, enabling virtual "thought experiments" that test and expand our understanding of multicellular systems and generate new testable hypotheses. This paper motivates and describes the grammar, offers a reference implementation, and demonstrates its use in developing both de novo mechanistic models and those informed …

Β-Catenin Functions As A Molecular Adapter For Disordered Cbaf Interactions, Yuen San Chan, Qinyu Gao, Sarah A Robinson, Wenzhi Wang, Ruzena Filandrova, Lisa-Maria Weinhold, Mario Loeza Cabrera, Miao Zhang, Chandra Shekar R Ambati, Antonio M Lerario, Nagireddy Putluri, Katja Kiseljak-Vassiliades, Margaret E Wierman, Mouhammed Amir Habra, Gary D Hammer, Vaclav Veverka, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction between BAF and divergent binding partners has remained unclear. Here, we tested the hypothesis that scaffold proteins augment BAF's binding repertoire by examining β-catenin (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast …

Organizational Climate And Decision Aid Sustainability In Lupus Care: Mixed Methods Study, Aizhan Karabukayeva, Larry R Hearld, Nathan W Carroll, Reena Kelly, Jasvinder A Singh

Faculty, Staff and Students Publications

Background: Digital decision aids (DAs) are increasingly used in health care to support shared decision-making and promote patient engagement. In the context of systemic lupus erythematosus (SLE), a complex autoimmune disease characterized by diverse symptoms and uncertain prognoses, DAs offer guidance to patients in navigating treatment risks and benefits. Although numerous studies have examined the initial implementation of evidence-based tools, there is limited evidence on the organizational factors that influence their long-term sustainability in clinical practice. This gap is particularly salient for digital interventions, where integration into routine workflows and ongoing use require alignment with clinic readiness and culture. This …

Current Mechanobiological Pathways And Therapies Driving Spinal Health, Rahul Kumar, Kyle Sporn, Harlene Kaur, Akshay Khanna, Phani Paladugu, Nasif Zaman, Alireza Tavakkoli

SKMC Student Presentations and Publications

Spinal health depends on the dynamic interplay between mechanical forces, biochemical signaling, and cellular behavior. This review explores how key molecular pathways, including integrin, yeas-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), Piezo, and Wingless/Integrated (Wnt) with β-catenin, actively shape the structural and functional integrity of spinal tissues. These signaling mechanisms respond to physical cues and interact with inflammatory mediators such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), driving changes that lead to disc degeneration, vertebral fractures, spinal cord injury, and ligament failure. New research is emerging that shows scaffold designs that can …

Targeted Proteomic Analysis Identifies Acvrl1 As A Marker Of Cerebral Edema In Aneurysmal Subarachnoid Hemorrhage, Bosco Seong Kyu Yang, Lena O'Keefe, Sarah Hinds, Hua Chen, Athziry Paz, Jude Savarraj, Han-Gil Jeong, Moon-Ku Han, Aaron Gusdon, Xuefang Sophie Ren, Spiros Blackburn, Huimahn Alex Choi

Faculty, Staff and Student Publications

Cerebral edema (CE) is a major component of early brain injury from aneurysmal subarachnoid hemorrhage (SAH). Despite the utility of blood-based protein markers, biomarkers targeting cerebral edema have yet to be developed. We performed a targeted proteomic search analyzing 141 proteins in plasma samples taken from 80 adult patients within 48 hours after aneurysmal rupture to identify plasma biomarkers of cerebral edema. The protein expression profiles were analyzed for associations with a higher level of the subarachnoid hemorrhage early brain edema score measured in admission computed tomography scans. Five differentially expressed proteins-brorin, ectodysplasin A2 receptor, layilin, scavenger receptor class A …

First-Line Pd-1 +/- Ctla-4 Blockade In Patients With Deficient Mismatch Repair And/Or Microsatellite Instability-High Metastatic Colorectal Cancer, Vincenzo Nasca, Gabriele Tinè, Julien Taieb, Sara Lonardi, Ben Boursi, Ofer Margalit, Lisa Salvatore, Romain Cohen, Javier Ros, Margherita Ambrosini, Koen Zwart, Jeanine Roodhart, Priya Jayachandran, Michael J Overman, Maria Elena Elez, Chiara Cremolini, David Tougeron, Miriam Koopman, Thierry André, Rosalba Miceli, Filippo Pietrantonio

Faculty, Staff and Student Publications

Background: Patients with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) show marked sensitivity to immune checkpoint inhibitors (ICIs). Dual PD-1/CTLA-4 blockade with nivolumab and ipilimumab showed superior progression-free survival (PFS) over chemotherapy and anti-PD-1 monotherapy, but data on treatment-naïve patients is not available yet.

Methods: This international multicenter study included patients with dMMR/MSI-H mCRC receiving either chemotherapy with or without biologics, or anti-PD-1 monotherapy, or dual PD-1/CTLA-4 blockade as a first-line treatment. Data were adjusted using inverse probability of treatment weighting (IPTW) to account for baseline imbalances. IPTW-adjusted survival and subgroup analyses were conducted.

Results: …

Silvestrol Inhibits Nasopharyngeal Carcinoma Cells And Synergizes With Cx‑5461: Insights From A Proteomics Study, Maelinda Daker, Munirah Ahmad, Alan Khoo, Lu Ping Tan, Siok-Fong Chin, Siaw San Hwang, Paul Neilsen

Department of Medical Oncology Faculty Papers

Nasopharyngeal carcinoma (NPC) is a cancer arising from the epithelial cells of the nasopharynx, which is rare in Western countries but extremely prevalent in Borneo and the Southern China region. Present-day hurdles in NPC treatment that lead to poor quality of life and poor survival include distant metastasis and resistance to chemoradiotherapy. Silvestrol and its 5'''-epimer, episilvestrol, are compounds isolated from the plant Aglaia stellatopilosa, which is endemic to Borneo. Silvestrol, a protein synthesis inhibitor, preferentially inhibits the translation of cancer-associated mRNAs. CX-5461 is an inhibitor of RNA polymerase I that catalyzes rRNA synthesis. The present study sought to …

Current Practices In The Study Of Biomolecular Acondensates: A Community Comment, Simon Alberti, Paolo Arosio, Robert B Best, Steven Boeynaems, Danfeng Cai, Rosana Collepardo-Guevara, Gregory L Dignon, Rumiana Dimova, Shana Elbaum-Garfinkle, Nicolas L Fawzi, Monika Fuxreiter, Amy S Gladfelter, Alf Honigmann, Ankur Jain, Jerelle A Joseph, Tuomas P J Knowles, Keren Lasker, Edward A Lemke, Kresten Lindorff-Larsen, Reinhard Lipowsky, Jeetain Mittal, Samrat Mukhopadhyay, Sua Myong, Rohit V Pappu, Karsten Rippe, Tatyana A Shelkovnikova, Anthony G Vecchiarelli, Susanne Wegmann, Huaiying Zhang, Mingjie Zhang, Chloe Zubieta, Markus Zweckstetter, Dorothee Dormann, Tanja Mittag

Duncan NRI Faculty and Staff Publications

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes, fundamentally changing the study of biology. The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics. As such, they are intimately related to aqueous two-phase systems and water-in-water emulsions. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials–. …