Medical Specialties Commons^™

Sers And Seira Detection Of Polycyclic Aromatic Hydrocarbons And Their Derivatives In Murine Tissues: Bioaccumulation And Clearance, Oara Neumann, Andrés B Sánchez-Alvarado, Weiwu Jiang, Guo Dong Zhou, Sachin B Jorveka, Parmeet Dhindsa, Nagireddy Putluri, Peter Nordlander, Melissa A Suter, Bhagavatula Moorthy, Naomi J Halas

Faculty, Staff and Students Publications

The toxicological effects of polycyclic aromatic hydrocarbons (PAHs) and polycyclic aromatic compounds (PACs) have attracted considerable research interest due to their known bioaccumulation. However, time-resolved and longitudinal studies that examine in vivo bioaccumulation and clearance remain limited. Here we use Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Infrared Absorption (SEIRA) spectroscopies to detect and track the presence of two PAHs: pyrene, benzo[a]pyrene, and one PAC: 5,12-naphthacenequinone, in murine organ tissues. Mice were exposed to a three-component mixture of these three chemicals, then their organs were collected at 24-, 48-, and 72- hours post-exposure. The accumulation of each of these chemicals in …

Dual Targeting Of Orphan Nuclear Receptors Nr4a1 And Nr4a2 For Nonhormonal Endometriosis Therapy, Wai Ning Tiffany Tsui, Yuri Park, Srijana Upadhyay, Da Mi Kim, Lei Zhang, Gus Wright, Amanuel Hailemariam, Arafat Rahman Oany, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Previous studies show that orphan nuclear receptor 4A1 (NR4A1) regulates endometriotic cell growth, survival, estrogen receptor β (ERβ), mechanistic target of rapamycin signaling and fibrosis. NR4A2 is also expressed in epithelial and stromal derived endometriotic cells, and in this study the effects of 1,1-bis(3'-indolyl)-(3,5-disubstitutedphenyl)methane (DIM-3,5) dual NR4A1/nuclear receptor 4A2 (NR4A2) ligands and knockdown of NR4A1 and NR4A2 were investigated. The dual NR4A1/2 DIM-3,5 analogs inhibited previously identified proendometriotic pathways and gene products, and they also inhibited TWIST1 and multiple markers associated with epithelial-to-mesenchymal transition (EMT). The results show that both NR4A1 and NR4A2 regulate the same pathways, including endometriotic cell …

Germline Determinants Of Toxicity And Efficacy In Patients With Large B-Cell Lymphoma Treated With Car T-Cell Therapy, Paolo Strati, Amanda Brandt, Anath C Lionel, Jared Henderson, Jason R Westin, Sherry Adkins, Elizabeth J Shpall, Partow Kebriaei, Jeremy Ramdial, Neeraj Saini, Sairah Ahmed, Christopher Flowers, Sattva S Neelapu, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Recent data have suggested that germline genetic aberrations can affect outcomes in patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CART). However, a comprehensive analysis of germline determinants of response and toxicity after CART has not yet been described.

Methods: Genome-wide genotyping was performed in 170 patients with LBCL treated with standard of care axicabtagene ciloleucel. Polygenic risk score instruments for blood cell traits and inflammatory markers were obtained from the PGS Catalog and analyzed using PRSice-2. Exploratory gene-based and genome-wide association study analyses were performed. Genetic ancestry of the patients with LBCL was …

Comprehensive Analysis Of The Tumor Targeting Efficiency Of Functionalized Nanoparticles In An Immunocompetent Environment, Nolan Jackson, Nasry Bouzeineddine, Daniel Cecchi, Safara Holder, Katrina Gee, Wayne Beckham, Sameh Basta, Sunil Krishnan, Devika B Chithrani

Faculty, Staff and Student Publications

The success of nanoparticle-based cancer therapeutics relies on their efficient tumor uptake and retention. Given this, improving nanoparticle localization in tumors is paramount to maximize their therapeutic potential. A common approach to achieve this is to functionalize nanoparticles with active targeting moieties that bind to specific tumor-associated receptors. Among these, arginine-glycine-aspartic acid (RGD) peptides have shown a potential to promote tumor accumulation by targeting the ανβ3 integrin receptor, a receptor commonly overexpressed by tumors owing to its role in promoting angiogenesis, metastasis and proliferation. Yet, its efficacy is commonly assessed using immunocompromised mice models. While useful, these models do not …

A Plain Language Summary Publication Of Patients’ Survival With Endometrial Cancer Treated With Dostarlimab Plus Carboplatin-Paclitaxel, Matthew A. Powell, Line Bjørge, Lyndsay Willmott, Zoltán Novák, Destin Black, Lucy Gilbert, Sudarshan Sharma, Giorgio Valabrega, Lisa M. Landrum, Martina Gropp-Meier, Ashley Stuckey, Ingrid Boere, Michael A. Gold, Yakir Segev, Sarah E. Gill, Christine Gennigens, Alexandra Sebastianelli, Mark S. Shahin, Bhavana Pothuri, Bradley J. Monk, Joseph Buscema, Robert L. Coleman, Brian M. Slomovitz, Kari L. Ring, Thomas J. Herzog, Morad Marco Balas, Matthew Grimshaw, Shadi Stevens, Dominic W. Lai, Carolyn Mccourt, Mansoor Raza Mirza

Abington Jefferson Health Papers

What is the purpose of this PLS-P? The purpose of this plain language summary of publication is to help you understand recent findings from Part 1 of the RUBY study (full name ENGOT-EN6/GOG3031/RUBY trial). • Researchers sometimes study new combinations of already approved individual treatments to see if the combinations work well together and if they are safe to prescribe to patients. • In Part 1 of the RUBY study, the combination of dostarlimab with carboplatin-paclitaxel was investigated to see how well it worked for patients with primary advanced or recurrent endometrial cancer when compared with patients who were given …

Complications Of Ovarian Metastases From Well-Differentiated Small Bowel Neuroendocrine Neoplasms: A Focus On Bowel And Ureteral Obstruction, Sydney J. Wellens, Nicholas J. Skill, Kevin M. Sullivan, Mary A. Maluccio, Kristen E. Limbach

School of Medicine Faculty Publications

Ovarian metastasis from small bowel neuroendocrine neoplasms (SBNENs) was traditionally considered rare, but more recent series have suggested a higher prevalence. This case series seeks to examine the features and outcomes of patients with neuroendocrine ovarian metastases (NOM). Female patients with histologically confirmed well-differentiated SBNENs were identified using a prospectively maintained database (2014–2024). The electronic medical record was reviewed for details of diagnosis, histopathology, biomarkers, and outcomes among patients with and without NOM. 175 patients met inclusion criteria. 35 patients (20 %) had ovarian metastasis; for this group, 31.4 % had small bowel obstruction only, 5.7 % had ureteral obstruction …

Apostel-R Recommendations For Reporting Retinal Optical Coherence Tomography Studies In Rodents, Frederike Cosima Oertel, Delia Cabrera Debuc, Peter A. Calabresi, Mei Chen, Christian Cordano, Michael Dietrich, Nicolas Feltgen, Oliver Gramlich, Ari J. Green, Janos Groh, Su-Chun Huang, Benjamin Knier, Thomas Korn, Letizia Leocani, Anat Loewenstein, Christian Van Oterendorp, Tunde Peto, Sven Schippling, Leopold Schmetterer, Steffen Schmitz-Valckenberg, Mathias W. Seeliger, Kenneth S. Shindler, Joel Schuman, Mustafa Sindi, Adnan Tufail, Jui-Kai Wang, Sebastian Wolf, Yuyi You, Martin Zinkernagel, Wolf Lagrèze, Philipp Albrecht

Department of Medicine Faculty Papers

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) in rodent models has been used to longitudinally image retinal changes, to define end points for more costly or time-consuming experiments, and to better understand the pathophysiology underlying OCT findings in human diseases. No standardization of rodent OCT reporting currently exists. Here, we aim to establish consensus recommendation for reporting results from retinal OCT studies in rodents.

METHODS: Initial recommendations were developed based on the APOSTEL criteria for quantitative OCT reporting in humans by a core team. Using a modified Delphi process, an expert panel of rodent OCT researchers (N = 31) …

Comparison Of Anterior And Posterior Surgical Approaches For Cervical Ossification Of The Posterior Longitudinal Ligament Stratified By Spinal Levels: A Systematic Review And Meta-Analysis, Seyed Danial Alizadeh, Sepehr Khosravi, Farzin Farahbakhsh, Vali Baigi, Moein Khormali, Mohsen Hajiqasemi, Zahra Eskandari, Mahgol Sadat Hassan Zadeh Tabatabaei, Amirmahdi Khayyamfar, Mohammad-Rasoul Jalalifar, Sepehr Armaghan, Masoud Pourghahramani Koltapeh, Zahra Ghodsi, Michael G. Fehlings, Alex R. Vaccaro, Vafa Rahimi-Movaghar

Rothman Institute Papers

OBJECTIVE: To compare the outcomes of anterior and posterior surgical approaches for treating cervical ossification of the posterior longitudinal ligament across multiple spinal levels, including 1-2 spinal levels, ≥ 3 levels, or studies that operated on both spinal levels, called mixed spinal levels.

METHODS: A search strategy using pertinent keywords was employed in the MEDLINE, Embase, Scopus, and Web of Science databases. Data on Modified Japanese Orthopaedic Association (mJOA) scores, radiographic outcomes, and complications were extracted. A random-effects meta-analysis, subgroup meta-analysis, and sensitivity analysis were performed.

RESULTS: Among 13 included studies, the anterior approach was statistically associated with improved C2-C7 …

A Case Of Granuloma Annulare Mimicking Candidal Intertrigo In The Groin, Scotty Smith, Patrice Perche, Leonard Gately

School of Medicine Faculty Publications

Granuloma annulare (GA) is a benign, non-infectious granulomatous skin condition of uncertain etiology, often presenting as annular erythematous plaques. While commonly localized to the hands and feet, GA has multiple clinical variants and can mimic other dermatologic conditions, leading to diagnostic challenges. We report a rare case of GA localized to the inguinal region in a 55-year-old female initially treated empirically for candidal intertrigo without improvement. Biopsy demonstrated interstitial histiocytic infiltrates dissecting between collagen bundles with increased dermal mucin, confirming a diagnosis of interstitial GA. The patient was subsequently treated with triamcinolone 0.1% ointment and hydroxychloroquine 200 mg twice daily …

Neighborhood Social Cohesion Associated With Chronic Liver Disease Prevalence And All-Cause Mortality, Tiange P. Zhang, Jennifer L. Dodge, Divya Ayyala-Somayajula, Norah A. Terrault

Division of Gastroenterology and Hepatology Faculty Papers

Background and Aims: Neighborhood social cohesion (NSC)—the degree of trust and solidarity within a community—may influence health through multiple pathways including shaping healthy norms, perception of safety, and stress. Whether NSC influences chronic liver disease (CLD) prevalence and associated mortality in the United States is unknown. Methods: Using 172,047 adults from the 2013–2018 National Health Interview Survey with linkage to National Death Index mortality data, NSC was measured using questions on help availability, accountability, trustworthiness, and connectedness among neighbors, with composite scores (4–16) categorized as minimal (4–7), low (8–10), moderate (11–13), and high (14–16). Logistic and Cox regression tested the …

Multimodal Reprogramming Of The Tumor Microenvironment By Mmr And Dual Checkpoint Blockade In Hepatocellular Carcinoma Models, Mulu Z. Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S. Shelton, Bahaa Mustafa, Camila C. Simoes, Murat Gokden, Isabelle R. Miousse, Kimberly J. Krager, Marjan Boerma, Alicja Urbaniak, Anuradha Kunthur, Sri Obulareddy, Joshua M. Eichhorn, Steven R. Post, Jean Christopher Chamcheu, Omeed Moaven, Chiswili Y. Chabu, Dan G. Duda, Matteo Conti, Bruno Nardo, Rang Govindarajan, Martin E. Fernandez-Zapico, Lewis R. Roberts, Mitesh J. Borad, Martin J. Cannon, Alexei G. Basnakian, Bolni M. Nagalo

School of Graduate Studies Faculty Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and …

Mechanistic Study Of Pexidartinib-Induced Toxicity In Human Hepatic Cells, Si Chen, Yuxi Li, Xilin Li, Nan Mei, Xiaobo He, Matthew S Bryant, Xuan Qin, Feng Li, Lei Guo

Faculty, Staff and Students Publications

Pexidartinib, a tyrosine kinase inhibitor, was approved by the U.S. Food and Drug Administration in 2019 for treating adult patients with symptomatic tenosynovial giant cell tumors. Because of its hepatotoxicity risks, pexidartinib received a boxed warning; however, mechanistic studies on this hepatotoxicity remain limited. In this study, we demonstrate that pexidartinib decreases cell viability in primary human hepatocytes and hepatic HepG2 cells. A 24-h treatment with pexidartinib led to apoptosis in HepG2 cells, as evidenced by increased caspase 3/7 activity and the induction of cleaved PARP and γ-H2A.X. Pexidartinib-induced endoplasmic reticulum (ER) stress was observed at early time points of …

Clinical Utility Of Diffusion Tensor Imaging In Sport-Related Concussion: A Systematic Review, Shiv Patil, Rithvik Kata, Serhat Aydin, Mert Karabacak, Konstantinos Margetis, Sotirios Bisdas

Student Papers, Posters & Projects

OBJECTIVE: Sport-related concussion (SRC) is a prevalent form of traumatic brain injury that is associated with long-term neurological and psychiatric impairment, particularly among athletes with a history of repetitive concussions. The biological variability of SRC's impact on the brain, as well as a lack of objective biomarkers to diagnose and prognosticate concussion, has prompted interest in advanced neuroimaging methods such as diffusion tensor imaging (DTI). By measuring disruptions in water diffusivity due to head trauma, DTI can detect alterations in white matter integrity that are not visualized by conventional imaging methods. This systematic review aims to synthesize major trends and …

Failure To Rescue After Surgery For Pancreatic Cancer: A Systematic Review And Narrative Synthesis Of Risk Factors And Safety Strategies, Masashi Uramatsu, Yoshikazu Fujisawa, Paul Barach, Hiroaki Osakabe, Moe Matsumoto, Yuichi Nagakawa

College of Population Health Faculty Papers

Background: Failure to rescue (FTR), defined as death after major postoperative complications, is a critical quality indicator in pancreatic cancer surgery. Despite advances in surgical techniques and perioperative care, FTR rates remain high and vary across institutions. Methods: This systematic review uses a narrative synthesis followed by PRISMA 2020. A PubMed search (1992-2025) identified 83 studies; after screening, 52 studies (2010-2025) were included. Eligible designs were registry-based, multicenter, single-center, or prospective audits. Given substantial heterogeneity in study designs, FTR definitions, and outcome measures, a narrative synthesis was performed; no formal risk-of-bias assessment or meta-analysis was conducted. Results: …

A Neuroimmune Cerebral Assembloid Model To Study The Pathophysiology Of Familial Alzheimer's Disease, Andrea Becerra-Calixto, Anik Banerjee, Huihui Fan, Chunfeng Tan, Eunyoung Lee, Louise D Mccullough, Juneyoung Lee

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is the leading cause of dementia globally. The accumulation of amyloid and tau proteins, neuronal cell death and neuroinflammation are seen with AD progression, resulting in memory and cognitive impairment. Microglia are crucial for AD progression as they engage with neural cells and protein aggregates to regulate amyloid pathology and neuroinflammation. Recent studies indicate that microglia contribute to the propagation of amyloid beta (Aβ) via their immunomodulatory functions including Aβ phagocytosis and inflammatory cytokine production. Three-dimensional cell culture techniques provide the opportunity to study pathophysiological changes in AD in human-derived samples that are difficult to recapitulate in …

Synaptic Transmission Promotes Brain Metastatic Outgrowth In Breast Cancer, Jayanta Mondal, Patrick Nylund, Prit Benny Malgulwar, William E Johnson, Jason T Huse

Faculty, Staff and Student Publications

This work demonstrates that normal neuron-to-neuron signaling machinery is hijacked by metastasizing cancer cells during their outgrowth in the central nervous system.

Quiescent Oxphos-High Triple-Negative Breast Cancer Cells That Persist After Chemotherapy Depend On Bcl-Xl For Survival, Slawomir Andrzejewski, Marie Winter, Leandro Encarnacao Garcia, Olusiji Akinrinmade, Francisco Madeira Marques, Emmanouil Zacharioudakis, Anna Skwarska, Julio Aguirre-Ghiso, Marina Konopleva, Guangrong Zheng, Susan A Fineberg, Daohong Zhou, Evripidis Gavathiotis, Tao Wang, Eugen Dhimolea

Faculty, Staff and Student Publications

The persistent residual tumor cells that survive after chemotherapy are a major cause of treatment failure, but their survival mechanisms remain largely elusive. These cancer cells are typically characterized by a quiescent state with suppressed activity of MYC and MTOR. We observed that the MYC-suppressed persistent triple-negative breast cancer (TNBC) cells are metabolically flexible and can upregulate mitochondrial oxidative phosphorylation (OXPHOS) genes and respiratory function ("OXPHOS-high" cell state) in response to DNA-damaging anthracyclines such as doxorubicin, but not to taxanes. The elevated biomass and respiratory function of mitochondria in OXPHOS-high persistent cancer cells were associated with mitochondrial elongation and remodeling, …

Effectiveness Of Vitamin D3 In Facilitating The Therapeutic Progression Of Healing Diabetic Foot Ulcers, Fatemeh Nouri, Sara Aghaei, Gülüzar Özbolat, Yusuf Döğüş, Mahdi Mirhamidi, Reza Rahimi Barghani, Amin Daemi

Chulalongkorn Medical Journal

Background: Today’s, diabetes and its complications have afflicted a large population all over the world, so that it is estimated that its prevalence in all age groups will reach from 2.8% in 2000 to 4.4% in 2030. It is well known that vitamin D may cause rapid wound healing and anti-inflammatory.

Objective: Regarding the importance of the quality of life of diabetic patients and the improvement of chronic diabetic foot ulcers, this paper aims to investigate the efficacy of vitamin D3 on the healing of diabetic foot ulcers. The present research is conducted as a randomized controlled trial.

Methods: …

The Comparison Of Radiation Attenuation Correction Techniques For Relative Renal Function In Renal Cortical Scintigraphy, Benchamat Phromphao, Sorasak Wanitchanan, Trai Chairat, Thunyaluk Sawatnatee, Tanawat Sontrapornpol

Chulalongkorn Medical Journal

Background: Renal cortical scintigraphy using Tc-99m Dimercaptosuccinic acid (Tc-99m DMSA) is the detection of cortical abnormalities. In addition, relative renal function (RRF) is performed by DMSA scintigraphy and estimated from the radiopharmaceutical uptake in both kidneys with radiation attenuation correction. Generally, attenuation correction is calculated from mathematic methods with kidney depth correction for an accurate renal function value.

Objective: The purpose of this research was to study the correlation of the RRF with radiation attenuation correction by geometric mean (GM) method and kidney depth correction by Beer-Lambert law equation.

Methods: Researchers studied in the spherical phantom, kidney phantom and patient’s …

Periodontal Status In Patients With Chronic Skin Diseases: A Pilot Study, Hao Nguyen, Thuy Nguyen, Thuy Vo, Huong Duong, Hoa Ho, Nhi Pham, Nguyen Pham, Nam Huynh

Chulalongkorn Medical Journal

Background: Many skin diseases, especially those that also involve the oral mucosa lesions might play an important role in the etiopathogenesis of oral health and mucocutaneous inflammation. The presence of these oral sores may make it more difficult to maintain good oral hygiene, which increases plaque accumulation and raises the risk of developing periodontal disease.

Objectives: This study aimed to evaluate and compare the periodontal status of chronic skin disease (CSD) patients with healthy controls.

Methods: 109 patients and 37 healthy subjects were included in this study. Parameters evaluated included bleeding on probing index (BOP), periodontal pocket depths (PPD), clinical …

Treatment Of Biopsy-Proven Laryngeal Squamous Cell Carcinoma In Situ, Praneet C. Kaki, Aman M. Patel, Lily Huang, Gavin Turner, Afash Haleem, Jason A. Brant, Robert M. Brody, Ryan M. Carey

SKMC Student Presentations and Publications

OBJECTIVE: To investigate the impact of clinical surveillance, primary radiotherapy, and primary surgery on overall survival (OS) in laryngeal carcinoma in situ (Cis).

METHODS: The 2006-2020 National Cancer Database was queried for adults with a biopsy-proven diagnosis of laryngeal Cis. Multivariable binary logistic and Cox proportional hazards regression models were implemented.

RESULTS: Of 3567 unique patients satisfying inclusion criteria, 514 (14.4%) underwent clinical surveillance, 1074 (30.1%) underwent primary radiotherapy, and 1979 (55.5%) underwent primary surgery. Receiving treatment at an academic/research facility was associated with higher odds of undergoing primary surgery compared to primary radiotherapy. Among 646 patients undergoing primary surgery …

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 …

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.

Factors Associated With Corrective Actions, Remediation, And Employment Termination Of Emergency Physicians, Lyndsay Tyler, Yachana Bhakta, Michael Gottlieb, Chadd K. Kraus, Terry Kowalenko, Yvette Calderon, Samuel M. Keim, Diane L. Gorgas, Deborah B. Diercks, Lewis S. Nelson

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Medical professionalism is fundamental to the delivery of high-quality patient care. There is a paucity of data to describe behaviors associated with negative professional and employment outcomes. This study examines common factors leading to corrective actions, remediation, and termination of emergency physicians (EPs).

METHODS: This was a cross-sectional survey sent to academic chairs in emergency medicine to identify factors for corrective actions, remediation, or termination of EPs. Survey items were piloted and response process validity gathered prior to administration. Data are reported as descriptive statistics.

RESULTS: 60 of 167 (36 %) members of the Association of Academic Chairs in …

Efficacy Of Erdafitinib Before Or After Enfortumab Vedotin In Fgfr3-Altered Advanced Urothelial Cancer: Analysis Of The Unite Collaborative Study, Cindy Y Jiang, Hyunsoo Hwang, Ilana Y Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Amy K Taylor, Amanda Nizam, Tanya Jindal, Michael J Glover, Ali Raza Khaki, Pedro C Barata, Charles B Nguyen, Eugene Oh, Nancy B Davis, Hannah Mabey, Christopher J Hoimes, Sean T Evans, Bashar Abuqayas, Emily Lemke, Irene Tsung, Wei Qiao, Deepak Kilari, Yousef Zakharia, Mehmet A Bilen, Matthew I Milowsky, Sumit A Shah, Shilpa Gupta, Hamid Emamekhoo, Joaquim Bellmunt, Ajjai S Alva, Petros Grivas, Pavlos Msaouel, Vadim S Koshkin, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Students Publications

Background: Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials.

Methods: UNITE is a multi-institutional retrospective study of patients with LA/mUC treated with novel targeted agents. All patients with FGFR3 alterations treated with EV only, erdafitinib then EV (Erda->EV), and EV then erdafitinib (EV->Erda) were included. Sequential treatment with EV and Erda was not required. Primary endpoints were observed response rates (ORR) and progression-free survival (PFS); secondary endpoint was overall survival (OS).

Results: …

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 …

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+ …

A Soft-Stiff Patterned Bioengineering Model Reveals Kinase Pathways Driving Directional Cell Migration In Pulmonary Arterial Hypertension, Tamanna Islam, Jacob Hooper, Xiaojun Zhang, Clarissa Garcia, Md Mahedi Hasan, David H Drewry, Mohammad Anwar Hossain, Taslim A Al-Hilal

Faculty, Staff and Student Publications

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules. Here, for the first time, we …

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.