Digital Commons Network^™

Methemoglobinemia-Induced Cardiac Dysfunction In A Pediatric Patient, Brian Drury, Chelsea Boyd, Kelsey Van Housen, Siraj Amanullah

Student Papers, Posters & Projects

Methemoglobinemia is a rare congenital or acquired cause of functional anemia resulting from oxidation of hemoglobin. Prompt recognition and treatment are critical to prevent tissue hypoxia and end-organ injury. While other complications are well described, cardiac dysfunction is rarely reported—especially in children. We present what, to our knowledge, is the first known case of methemoglobinemia-induced transient cardiac dysfunction—or “myocardial stunning— in a pediatric patient. This case underscores the importance of maintaining a high index of suspicion and assessing cardiac involvement in such patients. Early intervention can lead to full recovery and prevent long-term sequelae, even in the presence of multiorgan …

Biliverdin Reductase A Is A Major Determinant Of Protective Nrf2 Signaling, Chirag Vasavda, Ruchita Kothari, Navneet Ammal Kaidery, Suwarna Chakraborty, Sunil Jamuna Tripathi, Ryan S Dhindsa, Cristina Ricco, Shruthi Shanmukha, Samaneh Saberi, Julia E Lefler, Priyanka Kothari, Kalyani Chaubey, Adele M Snowman, Michael C Ostrowski, Eugenio Barone, Lakshminarayan M Iyer, L Aravind, Sudarshana M Sharma, Andrew A Pieper, Bobby Thomas, Solomon H Snyder, Bindu D Paul

Duncan NRI Faculty and Staff Publications

Biliverdin reductase A (BVRA), the terminal enzyme in heme catabolism, generates the neuroprotective and lipophilic antioxidant bilirubin. Here, we identify a nonenzymatic role for BVRA in redox regulation. Through phylogenetic, genetic, biochemical, and enzymatic assays, we found that BVRA exerts critical nonenzymatic antioxidant activity. Transcriptomic analyses further revealed that BVRA physically and genetically interacts with nuclear factor erythroid-derived factor-like 2 (NRF2), a major transcriptional regulator of cellular redox signaling. ChIP-seq and RNA-seq analyses reveal that BVRA and NRF2 coordinate the expression of antioxidant genes, many of which are typically dysregulated in neurodegenerative conditions such as Alzheimer's disease. Thus, this noncanonical …

Enhanced Piezo1 Function Contributes To The Pathogenesis Of Sickle Cell Disease, Luis O Romero, Manisha Bade, Laila Elsherif, Jada D Williams, Xiangmei Kong, Adebowale Adebiyi, Kenneth I Ataga, Shang Ma, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, leading to anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions that restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a nonselective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte …

Advances In Fret Methodologies For Probing Molecular Interactions, Geetika Verma, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Förster resonance energy transfer (FRET) has evolved into a powerful, quantitative approach for probing biomolecular structure, dynamics, and interactions. This research highlight brings together recent studies in Biophysical Journal that push the boundaries of traditional FRET. These innovations expand the spatial and temporal resolution of FRET, enabling its application to increasingly complex biological systems.

Phosphorylation Of Ryr1 At Ser2902 Decreases Ca2+ Leak In Skeletal Muscle And Susceptibility To Malignant Hyperthermia And Heat Stroke, Rachel Sue Zhen Yee, Chang Seok Lee, Ting Chang, Sung Yun Jung, Omar Yousif, Courtney Cavazos, John Colyer, Filip Van Petegem, George G Rodney, Susan L Hamilton

Faculty, Staff and Students Publications

The ryanodine receptor 1 (RYR1) is the sarcoplasmic reticulum (SR) Ca2+ release channel required for both skeletal muscle contraction and Ca2+ leak. Mutations in RYR1 cause malignant hyperthermia susceptibility (MHS) and enhanced sensitivity to heat stroke (ESHS), which can result in death due to excessive skeletal muscle thermogenesis upon exposure to volatile anesthetics or heat. Here, we investigated the molecular and physiological functions of phosphorylation of RYR1 at Ser2902 by the kinase SPEG (striated muscle preferentially expressed protein). Muscle from SPEG-deficient mice expressing RYR1 with a Ser2902 →Asp2902 (S2902D) point mutation to mimic phosphorylation by SPEG showed decreased SR Ca2+ …

The Latest In Resuscitation Research: Highlights From The 2024 American Heart Association's Resuscitation Science Symposium, Gabriela M Galli, Aarthi Kaviyarasu, Sachin Agarwal, Catherine R Counts, Tommaso Scquizzato, Betty Yang, Clark G Owyang, Ryan Coute, Simon Orlob, Lindsay Shepard, Saleem Halablab, James Horowitz, Sarah Perman, Ryan Morgan, Anne Grossestreuer, Jacob Vine, Nicholas Johnson, Luke Andrea, Ari Moskowitz, Benjamin Abella, Cameron Dezfulian, Walid H Farooqi, Felipe Teran

Faculty, Staff and Students Publications

No abstract provided.

Atg Conjugation-Dependent/Independent Mechanisms Underlie Lysosomal Stress-Induced Tfeb Regulation, Shiori Akayama, Takayuki Shima, Tatsuya Kaminishi, Mengying Cui, Jlenia Monfregola, Kohei Nishino, Andrea Ballabio, Hidetaka Kosako, Tamotsu Yoshimori, Shuhei Nakamura

Duncan NRI Faculty and Staff Publications

TFEB, a master regulator of autophagy and lysosomal biogenesis, is activated by several cellular stresses including lysosomal damage, but its underlying mechanism is unclear. TFEB activation during lysosomal damage depends on the ATG conjugation system, which mediates lipidation of ATG8 proteins. Here, we newly identify ATG conjugation-independent TFEB regulation that precedes ATG conjugation-dependent regulation, designated Modes I and II, respectively. We reveal unique regulators of TFEB in each mode: APEX1 in Mode I and CCT7 and/or TRIP6 in Mode II. APEX1 interacts with TFEB independently of the ATG conjugation system, and is required for TFEB stability, while both CCT7 and …

Atg16l1 Controls Mammalian Vacuolar Proton Atpase, Thabata L A Duque, Masroor Paddar, Einar Trosdal, Ruheena Javed, Lee Allers, Michal H Mudd, Prithvi Akepati, Soumya R Mishra, Michelle Salemi, Brett Phinney, Shawn B Bratton, Thomas Wileman, Vojo Deretic

Faculty, Staff and Student Publications

The mechanisms governing mammalian proton pump V-ATPase function are of fundamental and medical interest. The assembly and disassembly of cytoplasmic V1 domain with the membrane-embedded V0 domain of V-ATPase is a key aspect of V-ATPase localization and function. Here, we show that the mammalian protein ATG16L1, primarily appreciated for its role in canonical autophagy and in noncanonical membrane atg8ylation processes, controls V-ATPase. ATG16L1 knockout elevated V-ATPase activity, increased V1 presence on endomembranes, and increased the number of acidified intracellular compartments. ATG16L1's ability to efficiently bind V-ATPase was required for its inhibitory role in endolysosomal acidification and for control of Mycobacterium …

Strain-Specific Variability In Viral Kinetics, Cytokine Response, And Cellular Damage In Air-Liquid Cultures Of Human Nasal Organoids After Infection With Sars-Cov-2, Gina M Aloisio, Trevor J Mcbride, Letisha Aideyan, Emily M Schultz, Ashley M Murray, Anubama Rajan, Erin G Nicholson, David Henke, Laura Ferlic-Stark, Amal Kambal, Hannah L Johnson, Elina A Mosa, Fabio Stossi, Sarah E Blutt, Pedro A Piedra, Vasanthi Avadhanula

Faculty, Staff and Students Publications

SARS-CoV-2 variants have demonstrated distinct epidemiological patterns and clinical presentations throughout the COVID-19 pandemic. Understanding variant-specific differences at the respiratory epithelium is crucial for understanding their pathogenesis. Here, we utilized human nasal organoid air-liquid interface (HNO-ALI) cell cultures to compare the viral replication kinetics, innate immune response, and epithelial damage of six different strains of SARS-CoV-2 (B.1.2, WA, Alpha, Beta, Delta, and Omicron). All variants replicated efficiently in HNO-ALIs, but with distinct replication kinetic patterns. The Delta variant exhibited delayed replication kinetics, achieving a steady state at 6 days post-infection compared to 3 days for other variants. Cytokine analysis revealed …

Improved Allele Frequencies In Gnomad Through Local Ancestry Inference, Pragati Kore, Michael W Wilson, Grace Tiao, Katherine Chao, Philip W Darnowsky, Nicholas A Watts, Jessica Honorato Mauer, Samantha M Baxter, Genome Aggregation Database Consortium, Heidi L Rehm, Mark J Daly, Konrad J Karczewski, Elizabeth G Atkinson

Faculty, Staff and Students Publications

The Genome Aggregation Database (gnomAD) is a foundational resource for allele frequency data, widely used in genomic research and clinical interpretation. However, traditional estimates rely on individual-level genetic ancestry groupings that may obscure variation in recently admixed populations. To improve resolution, we applied local ancestry inference (LAI) to over 27 million variants in two admixed groups: Admixed American (n = 7612) and African/African American (n = 20,250), deriving ancestry-specific allele frequencies. We show that 78.5% and 85.1% of variants in these groups, respectively, exhibit at least a twofold difference in ancestry-specific frequencies. Moreover, 81.49% of variants with LAI information would …

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Vaccine Value Profile For Schistosomiasis, Gavin Yamey, Kaci Kennedy Mcdade, Roy M Anderson, Sarah M Bartsch, Maria Elena Bottazzi, David Diemert, Peter J Hotez, Bruce Y Lee, Donald Mcmanus, Adebayo J Molehin, Meta Roestenberg, David Rollinson, Afzal A Siddiqui, Miriam Tendler, Joanne P Webster, Hong You, Raphaël M Zellweger, Caroline Marshall

Faculty, Staff and Students Publications

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also …

All-Optical Voltage Interrogation For Probing Synaptic Plasticity In Vivo, Jacques Carolan, Michelle A Land, Xiaoyu Lu, Maxime Beau, Dimitar Kostadinov, François St-Pierre, Beverley A Clark, Michael Häusser

Faculty, Staff and Students Publications

Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) …

A Needed Nomenclature For Nucleosomes, Michael-Christopher Keogh, Genevieve Almouzni, Andrew J Andrews, Karim-Jean Armache, Cheryl H Arrowsmith, Sung Hee Baek, Mark T Bedford, Emily Bernstein, Jacques Côté, Yael David, John M Denu, Beat Fierz, Benjamin A Garcia, Karen C Glass, Or Gozani, Kristian Helin, Steven Henikoff, Ole N Jensen, Steven Z Josefowicz, Neil L Kelleher, Tatiana G Kutateladze, Herbert H Lindner, Chao Lu, Karolin Luger, Parag Mallick, Catherine A Musselman, Tom W Muir, Ljiljana Paša-Tolić, Robert Schneider, Xiaobing Shi, Yang Shi, Simone Sidoli, Lloyd M Smith, Jessica K Tyler, Cynthia Wolberger, Jerry L Workman, Brian D Strahl, Nicolas L Young

Faculty, Staff and Student Publications

Histone post-translational modifications (PTMs) are crucial to eukaryotic genome regulation, with a range of reported functions and mechanisms of action. Though often studied individually, it has long been recognized that the modifications function by combinatorial synergy or antagonism. Interplay may involve PTMs on the same histone, within the same nucleosome (containing a histone octamer), or between nucleosomes in higher-order chromatin. Given this, the field must distinguish ever greater complexity, and the context in which it is studied, with brevity and precision. The proteoform was introduced to define individual forms of a protein by sequence and PTMs, followed by the nucleoform …

Functional Effects Of Heavy Metal Exposures On N6-Methyladenosine (M6a) Methylation And Other Epitranscriptomic Modifications In The Central Nervous System, Niraj Lodhi, Lauren Powell, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Among different RNA methylations, N6-methyladenosine (m6A) is the most abundant in the brain and determines the fate of RNA through reversible processes using methyltransferases, demethylases, and methyl-binding proteins. The reversibility of m6A is an emerging regulatory mechanism for gene expression, regulating many aspects of RNA metabolism and influencing learning and memory processes. Global m6A profiles are dynamically modified via the activity of various writers, readers, and erasers. However, m6A alterations from exposure to heavy metals, including the metals lead (Pb), cadmium (Cd), cobalt (Co), and manganese (Mn) and the metalloid arsenic (As), and the impact on brain function, are not …

Educating Future Nurse Practitioners And Physician Associates On Pretreatment Of Swallowing In Head And Neck Cancer, Hannah M. Berk, Erin L. O'Bryan, Imran Musaji, Carly A. Thomas, Jamie Harrington

Teaching and Learning in Communication Sciences & Disorders

Head and neck cancer treatment frequently results in long-term severe swallowing deficits, often requiring feeding tube dependency. Patients who have completed swallowing exercise programs before and during cancer treatment experienced more positive swallowing outcomes, but most patients are not referred for swallowing intervention early enough in their care to prevent long-term deficits. This student research project aimed to measure health profession students’ knowledge of swallowing pretreatment for head and neck cancer patients and to investigate the impact of an educational module developed and presented by a Communication Sciences and Disorders graduate student to improve knowledge and awareness of this clinical …

Methylation Of The Dat1 Dopamine Transporter Gene In Combat Sport Athletes: Associations With Impulsivity And Reward Sensitivity, Milena Lachowicz, Remigiusz Recław, Aleksandra Suchanecka, Krzysztof Chmielowiec, Elżbieta Grzywacz, Jolanta Chmielowiec, Kinga Łosińska, Anna Grzywacz

Baltic Journal of Health and Physical Activity

Epigenetic mechanisms, such as DNA methylation, modulate behavioral traits, including impulsivity and reward sensitivity. The dopamine transporter gene (DAT1) plays a key role in dopaminergic function and is associated with self-regulation, attention, and the trait of addiction. This study summarized the DAT1 methylation status in patients practicing combat sports and its association with impulsivity, ADHD symptoms, and consequence sensitivity. One hundred control subjects were recruited using the Barratt Impulsivity Scale (BIS), the ADHD scale, and the Opportunity Response Scale. DAT1 methylation was measured using the bisulfite ionization method. A correlation analysis was performed with the comparison group. Athletes …

International Headache Society Evidence-Based Guidelines On The Use Of Non-Invasive Neuromodulation Devices For The Acute And Preventive Treatment Of Migraine, Hsiangkuo Yuan, Serena L. Orr, Mohammad A. M. Al-Karagholi, Messoud Ashina, Fred Cohen, Hans-Christoph Diener, David W. Dodick, Rigmor Højland Jensen, Michael J. Marmura, Daniele Martinelli, Manjit S. Matharu, Anja S. Petersen, Patricia Pozo-Rosich, Simona Sacco, Lucy Simmonds, Cristina Tassorelli, Stewart J. Tepper, Gisela M. Terwindt, Shuu-Jiun Wang, Jiunn-Tyng Yeh, Stephen D. Silberstein

Department of Jefferson Headache Center Papers and Presentations

ObjectiveTo develop evidence-based clinical practice guidelines for non-invasive neuromodulation devices in acute and preventive migraine treatment.MethodsA systematic review was conducted across six databases from 1946 to April 2025. Randomized controlled trials evaluating Food and Drug Administration-cleared or Conformité Européenne (CE)-marked non-invasive neuromodulation devices were included. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and recommendations were developed through consensus following GRADE Evidence-to-Decision frameworks. The working group comprised 15 senior members and six junior members.ResultsFrom 1536 initial records, 15 studies met the inclusion criteria and were finally used to develop evidence-based recommendations. …

Issue 15: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls, Kristin Lytal Pharmd, Mspgx, Stephanie Subart Pharmd

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 15

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.

Topics:

2025 Guidelines for ANCA Vasculitis

Airway Scaffolds for Emphysema: Six-Month BREATHE TRIAL Results

Tackling Emphysema-Related Hyperinflation: Scaffolds, Valves, or Vapor? How They Work?

Bactericidal vs. Bacteriostatic Antibiotics in Critically Ill Patients

Modified Cuff Leak Test (CLT) …

Low Vitamin D Diet Effects On Rna Expression In Kidney And Mammary Tissue Of Mus Musculus (Mice), Ibilola Fasogbon, Graham Read, Adriana Duraki, Larisa Nonn

Annual Student Research Poster Session

Vitamin D is a steroid hormone whose active form binds to Vitamin D Receptors (VDR), triggering cancer-associated pathways involved in inducing apoptosis, inhibiting inflammation, improving immunity, and regulating cell proliferation. Ongoing studies have shown a significant correlation between Vitamin D deficiency and the development of aggressive prostate cancer. African American men are more likely to experience vitamin D deficiency, develop prostate cancer at a high rate, and have a higher mortality rate than their non-Hispanic white counterparts. African American women are also disproportionately burdened with aggressive breast cancer and have higher rates of vitamin D deficiency. Understanding how a low …

Human Transferrin Receptor Bispecific Trem2 Antibody Creation And Its Insightful Use In Alzheimer's Disease, Amelia Mclaren, June Javens-Wolfe

Annual Student Research Poster Session

Alzheimer’s disease (AD) is the leading cause of dementia, affecting an estimated 7.2 million seniors in the United States. AD can develop in the brain for twenty years or more before symptoms appear, such as memory loss, which could enable a diagnostic window for intervention. AD causes neurons to be damaged or destroyed due to the accumulation of amyloid-beta protein fragments and an abnormal form of tau protein. The protein Transmembrane Receptor Expressed by Myeloid Cells, TREM2, is essential in regulating the microglial response to amyloid-beta and tau accumulation in the AD brain. Microglia, the brain’s resident immune cell, has …

Cervical Hpv 18 Detection Is Associated With High-Grade Cervical Dysplasia In Kenyan And Ugandan Women Living With Hiv, Miriam Nakalembe, Collins Mpamani, Jane Namugga, Carolyn Nakisige, Grace Banturaki, Phillip Tonui, Peter Itsura, Omenge Orango, Kapten Muthoka, Anthony Ngeresa

Obstetrics and Gynaecology, East Africa

Objectives Cervical cancer, caused by “high-risk” (HR) HPV, is the most common malignancy and the leading cause of cancer deaths among women living in Kenya and Uganda. Women living with HIV (WLWH) are at a high risk for HR-HPV infection. This longitudinal, observational cohort analysis was conducted to identify factors that are important among WLWH in prediction of cervical intraepithelial neoplasia grades 2 or 3 (CIN2/3).

Methods Data of this analysis was based on a study of HPV natural history and cervical cancer among Kenyan and Ugandan WLWH. Demographic, behavioral and biological data were collected; HR-HPV DNA testing of cervical …

Cervical Hpv 18 Detection Is Associated With High-Grade Cervical Dysplasia In Kenyan And Ugandan Women Living With Hiv, Miriam Nakalembe, Collins Mpamani, Jane Namugga, Carolyn Nakisige, Grace Banturaki, Phillip Tonui, Peter Itsura, Elkanah Orang'o, Kapten Muthoka, Anthony Ngeresa

Obstetrics and Gynaecology, East Africa

Objectives Cervical cancer, caused by “high-risk” (HR) HPV, is the most common malignancy and the leading cause of cancer deaths among women living in Kenya and Uganda. Women living with HIV (WLWH) are at a high risk for HR-HPV infection. This longitudinal, observational cohort analysis was conducted to identify factors that are important among WLWH in prediction of cervical intraepithelial neoplasia grades 2 or 3 (CIN2/3).

Methods Data of this analysis was based on a study of HPV natural history and cervical cancer among Kenyan and Ugandan WLWH. Demographic, behavioral and biological data were collected; HR-HPV DNA testing of cervical …

Positive Depression Screen Among Pregnant Women Attending Antenatal Clinic At Aga Khan University Hospital, Michael Maina Muriithi

Master of Medicine in Obstetrics and Gynecology

Introduction: One in seven women experience peripartum depression, a common disorder that can occur during pregnancy or in the postpartum phase. Women are particularly vulnerable to depressive symptoms during pregnancy and the immediate postpartum period due to physiological changes during pregnancy as well as other sociocultural stressors. Peripartum depression is associated with significant maternal and perinatal adverse outcomes, including self-neglect, substance use, preterm birth, low birth weight and poor neurocognitive development, in offspring. There is a need to understand the prevalence and factors associated with depressive symptoms during pregnancy to improve maternal and neonatal outcomes. To our knowledge, this …

Concurrent Local Therapy Extends Clinical Benefit Of Tebentafusp In Metastatic Uveal Melanoma Patients, Tristan L. Lim, Kamaneh Montazeri, Eric Wehrenberg-Klee, Antoine Desilets, Rino S. Seedor, Marlana Orloff, Takami Sato, Michael Caplan, Mariam El-Ashmawy, Benjamin Izar, Shaheer Khan, Inderjit Mehmi, Aleigha Lawless, Theodore S. Hong, Omid Hamid, Richard D. Carvajal, Alexander Shoushtari, Ryan J. Sullivan

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp has significantly improved overall survival in HLA-A*02:01+ metastatic uveal melanoma (mUM) patients even in those with a best objective response of progressive disease. Thus, strategies to maintain tebentafusp therapy are critical. Here, we examine the efficacy and safety of adding concurrent local therapy (CLT) to tebentafusp upon radiological progression with tebentafusp alone.

PATIENTS AND METHODS: This multicenter retrospective study included mUM patients treated with tebentafusp and CLT, consisting of extrahepatic soft tissue irradiation and liver-directed therapies (LDTs). Efficacy of target and nontarget sites were assessed per RECIST version 1.1. PFS with tebentafusp alone (PFS1) was compared to that …

Escape Of Kdm6a From X Chromosome Is Detrimental To Ischemic Brains Via Irf5 Signaling, Conelius Ngwa, Afzal Misrani, Kanaka Valli Manyam, Yan Xu, Shaohua Qi, Romana Sharmeen, Juneyoung Lee, Long-Jun Wu, Louise Mccullough, Fudong Liu

The Brown Foundation: Institute of Molecular Medicine

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia, respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17–20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the …

Diabetes-Related Foot Complications And Socioeconomic Influences Among Hispanic Males In South Texas: A Scoping Review, Mariana J. Rodriguez, Demian Rodriguez, Amanda Killeen

School of Podiatric Medicine Publications

Introduction: Diabetes mellitus is the 7th leading cause of death in the U.S. and 6th in Texas. South Texas counties have higher diabetes rates than state and national averages. This complex, progressive disease affects multiple body systems and can lead to serious complications, especially in the lower extremities. Uncontrolled diabetes is often associated with diabetic foot ulcers (DFU), foot infections, and lower extremity amputations (LEA). South Texas, predominantly Hispanic American, is disproportionately affected. This demographic faces clinical barriers due to a lack of cultural understanding, highlighting the need for culturally sensitive healthcare workers such as promotoras. This study aimed to …

Une Com Research And Scholarship Fall Forum October 2025, Une Com Research & Scholarship

Osteopathic Student Research Symposia

Program including abstracts from the University of New England College of Osteopathic Medicine’s 2025 Research and Scholarship Fall Forum.

Supplemental content: List of award winners.

Diabetes-Related Foot Complications And Socioeconomic Influences Among Hispanic Males In South Texas: A Scoping Review, Mariana J. Rodriguez, Demian Rodriguez, Amanda L. Killeen

School of Podiatric Medicine - Student Research

Introduction: Diabetes mellitus is the 7^th leading cause of death in the United States and is 6^th in the state of Texas. Counties from South Texas are primarily affected with higher rates of diabetes than both the state and national average. Diabetes mellitus is a complex and progressive disease which can affect multiple systems of the body, leading to serious complications if untreated, especially in the lower extremities. Uncontrolled diabetes is often associated with diabetic foot ulcers (DFU), foot infections, and lower extremity amputations (LEA). South Texas is a region predominantly populated by Hispanic Americans who are disproportionally …

Decorin Evokes A Pro-Lysosomal Pathway In Lymphatic Endothelial Cells, Gabriel J. Pascal, Dipon K. Mondal, Sadie Kim, Christopher Xie, Devanarayanan Siva Sankar, Jörn Dengjel, Renato V. Iozzo

Kimmel Cancer Center Faculty Papers

The lymphatic system is critical to the body's immune and circulatory system, and lymphangiogenesis, the development of new lymphatic vessels from pre-existing ones is a significant process capitalized upon by cancer during tumorigenesis. Decorin is a small leucine-rich proteoglycan which we have previously shown to be anti-tumorigenic and a suppressor of lymphangiogenesis. We have also shown that decorin exercises its anticancer properties through its ability to evoke autophagy. Through a comprehensive and unbiased proteomic analysis, we explored the implications of decorin exposure on protein expression within mouse lymphatic endothelial cells. We discovered that decorin enriches several protein pathways, notably proteasomal …