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Collagen Type Ii-Targeting Lentiviral Gene Therapy For Mucopolysaccharidosis Iva, Betul Celik, Sampurna Saikia, Shaukat Khan, Krishna Sai Musini, Shunji Tomatsu Dec 2025

Collagen Type Ii-Targeting Lentiviral Gene Therapy For Mucopolysaccharidosis Iva, Betul Celik, Sampurna Saikia, Shaukat Khan, Krishna Sai Musini, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS IVA) is caused by pathogenic variations in the GALNS gene, leading to the accumulation of glycosaminoglycans in tissues and causing progressive skeletal lesions. While conventional lentiviral vectors (LVs) provide long-term stable expression, they do not deliver therapeutic levels to bone and cartilage. We hypothesized that engineering the LV envelope with a collagen type II-targeting peptide (WYRGRL) increases the binding affinity of the LVs for bone and cartilage. These modified vectors carrying the CBh and COL2A1 promoters delivered the GALNS gene to MPS IVA newborn mice via intravenous (IV) or intraarticular (IA) administration. The peptide-modified LVs exhibited markedly increased …


Tumor Biology And Access To Care And Metastatic Breast Cancer Outcomes, Matthew R. Dunn, Sarah C. Van Alsten, Marc A. Emerson, Katherine Reeder-Hayes, Terry Hyslop, Melissa A. Troester Dec 2025

Tumor Biology And Access To Care And Metastatic Breast Cancer Outcomes, Matthew R. Dunn, Sarah C. Van Alsten, Marc A. Emerson, Katherine Reeder-Hayes, Terry Hyslop, Melissa A. Troester

Kimmel Cancer Center Faculty Papers

PURPOSE: To understand how access to care influences metastatic breast cancer burden (MBC) while accounting for molecular tumor characteristics, and identify interventions to reduce metastatic disease burden.

METHODS: The Carolina Breast Cancer Study is a population-based cohort with invasive breast cancer (diagnosed 2008-2013). Both de novo metastasis (stage IV at diagnosis) and distant recurrence were evaluated (12 years of follow-up. Tumor data were from medical records, pathology reports, and RNA expression data. Social variables and access to care were from participant surveys. Generalized linear models were used to estimate associations of biological and access characteristics with MBC; Cox models were …


Sex Differences In The Association Of Vascular Risk And Apoe Genotype With Cognitive Decline And Dementia: Evidence From A U.S. Longitudinal Study, Longjian Liu, Jintong Hou, Saishi Cui, Xiaopeng Zhao, Zuolu Liu, J. Craig Longenecker, Nathalie S May, Jin Jun Luo, Rose Ann Dimaria-Ghalili, Howard J. Eisen Dec 2025

Sex Differences In The Association Of Vascular Risk And Apoe Genotype With Cognitive Decline And Dementia: Evidence From A U.S. Longitudinal Study, Longjian Liu, Jintong Hou, Saishi Cui, Xiaopeng Zhao, Zuolu Liu, J. Craig Longenecker, Nathalie S May, Jin Jun Luo, Rose Ann Dimaria-Ghalili, Howard J. Eisen

Division of Cardiology Faculty Papers

BACKGROUND: Sex differences in the association between vascular factors and cognitive outcomes remain unclear. We aimed to investigate the associations of blood pressure metrics (hypertension, systolic blood pressure [SBP), pulse pressure, ankle and brachial pressures, and ankle to brachial pressure index [ABI]) with the risk of cognitive decline and dementia.

METHODS: We conducted a population-based longitudinal analysis using data from the Atherosclerosis Risk in Communities (ARIC) study (begun in 1987-1989) in the United States. We analyzed a total of 12,268 participants aged 45-64 years who had validated exposure measurements, cognitive function tests (first administrated 1990-1992), and followed up for incidence …


Anti-Saccade Error Rates Are Associated With Somatic Depressive Symptoms In Cocaine Use Disorder, Constanza De Dios, Heather E Webber, Margaret C Wardle, Jin H Yoon, Michelle A Patriquin, Jessica N Vincent, Joy M Schmitz, Scott D Lane Dec 2025

Anti-Saccade Error Rates Are Associated With Somatic Depressive Symptoms In Cocaine Use Disorder, Constanza De Dios, Heather E Webber, Margaret C Wardle, Jin H Yoon, Michelle A Patriquin, Jessica N Vincent, Joy M Schmitz, Scott D Lane

Faculty, Staff and Student Publications

Background: Inhibitory control deficits are associated with cocaine use disorder (CUD) development and maintenance. Additionally, drug use and inhibitory control can be negatively affected by depressive symptoms, including somatic factors like sleep disturbance and fatigue.

Aim: The current study assessed the relationship between inhibitory control and depressive symptoms among individuals initiating CUD treatment. We examined associations among anti-saccade response inhibition performance, total scores on the Beck Depression Inventory-II (BDI-II), and individual BDI-II items.

Methods: N = 101 patients enrolled in a clinical trial for CUD completed drug-specific anti-saccade and depression (BDI-II) measures prior to treatment. Generalized linear models tested the …


Incidental Cardiac Metastasis In Breast Carcinoma, Yaomin Chen, Haibo Wang, Zhiyan Fu, Ellen Elizabeth Connor Dec 2025

Incidental Cardiac Metastasis In Breast Carcinoma, Yaomin Chen, Haibo Wang, Zhiyan Fu, Ellen Elizabeth Connor

School of Medicine Faculty Publications

Background and Clinical Significance: Metastatic breast cancer is a major global health burden, with common metastatic sites including the bones, lungs, liver, and brain. Cardiac metastasis is rare and often clinically silent, leading to underdiagnosis. Recognizing cardiac involvement, even when asymptomatic, is important for understanding the full extent of disease and ensuring optimal patient care. Case Presentation: We report the case of a woman with advanced breast carcinoma who showed no clinical or imaging evidence of cardiac involvement throughout the course of her illness. Following her death from progressive metastatic disease, an autopsy revealed metastatic carcinoma infiltrating the myocardium and …


Systemic Sclerosis-Associated Interstitial Lung Disease: Improved Understanding And Advances In Management, Amit Syal, Chris T. Derk Dec 2025

Systemic Sclerosis-Associated Interstitial Lung Disease: Improved Understanding And Advances In Management, Amit Syal, Chris T. Derk

Student Papers, Posters & Projects

Interstitial lung disease (ILD), a common manifestation of systemic sclerosis (SSc), has the highest organ-specific morbidity and mortality, particularly in patients with diffuse cutaneous SSc (dcSSc). Recent advances in diagnostics-including artificial intelligence (AI)-enhanced high-resolution computed tomography (HRCT) and biomarkers such as Krebs van den Lungen (KL)-6-have enabled earlier detection and monitoring of disease progression. Therapeutically, the approval of antifibrotics like nintedanib (NINT) and immunomodulators such as tocilizumab (Toci) has significantly expanded treatment options. Updated international guidelines from the American College of Rheumatology (ACR), American College of Chest Physicians (CHEST), American Thoracic Society (ATS), and European league against Rheumatism (EULAR) now …


Association Between Vitamin D And Cholesterol In Post-Acne Hypertrophic Scars And Keloids: A Cross-Sectional Study, Yuli Kurniawati, Yulia Farida Yahya, Sarah Diba, Rina Novriani, Hasbiallah Yusuf, Ekta Martgaredta Dec 2025

Association Between Vitamin D And Cholesterol In Post-Acne Hypertrophic Scars And Keloids: A Cross-Sectional Study, Yuli Kurniawati, Yulia Farida Yahya, Sarah Diba, Rina Novriani, Hasbiallah Yusuf, Ekta Martgaredta

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Post-acne hypertrophic scars and keloids result from abnormal wound healing within the pilosebaceous unit. Ruptured microcomedones create wounds that can lead to prolonged inflammation, increased collagen synthesis, and fibrinolysis inhibition, resulting in elevated scar tissue in acne lesions. Vitamin D deficiency can lead to prolonged inflammation and damage to dermal collagen. High total cholesterol levels can lead to excessive sebum production, exacerbating inflammation and fibrosis. This study aimed to determine the association between serum vitamin D and total cholesterol levels with scar severity in patients with post-acne hypertrophic scars and keloids.

Methods: This analytical cross-sectional study was conducted at …


Extensive Superficial Dermatomycosis Caused By Cladophialophora Sp., A Deep Mycosis Pathogen: A Case Report, Nikko Vanda Limantara, Agnes Sri Siswati, Flandiana Yogianti Dec 2025

Extensive Superficial Dermatomycosis Caused By Cladophialophora Sp., A Deep Mycosis Pathogen: A Case Report, Nikko Vanda Limantara, Agnes Sri Siswati, Flandiana Yogianti

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Superficial dermatomycosis, predominantly caused by dermatophytes, affects approximately 20–25% of the global population. However, non-dermatophytic fungi, such as Cladophialophora species (sp.), can also cause similar cutaneous infections. Although less common, these organisms are particularly concerning in immunocompromised individuals.

Case Illustration: A 66-year-old immunocompromised male presented with widespread pruritic and erythematous patches, initially misdiagnosed as tinea corporis. Despite receiving standard antifungal therapy, his condition persisted. Further investigation through fungal culture identified Cladophialophora sp., which was resistant to common antifungal agents such as fluconazole, itraconazole, and ketoconazole. However, the fungus was sensitive to terbinafine, which has …


Successful Management Of Generalized Pustular Psoriasis With Cyclosporine In Hiv-Infected Patient, Rasinta Ayudya Deltania, Anggun Putri Yuniaswan Dec 2025

Successful Management Of Generalized Pustular Psoriasis With Cyclosporine In Hiv-Infected Patient, Rasinta Ayudya Deltania, Anggun Putri Yuniaswan

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Generalized pustular psoriasis (GPP) can be associated with human immunodeficiency virus (HIV) infection, making its management more challenging and complex. This case report aims to evaluate the effectiveness and safety of cyclosporine in HIV-associated GPP.

Case illustration: A 31-year-old male with a six-year history of HIV on antiretroviral therapy presented with rapidly spreading erythematous plaques with scaling and patches, along with “lakes of pus”, involving 50% of the body surface area (BSA). He reported oral burning, dysgeusia, and odynophagia; tongue Gram stain showed budding yeast and pseudohyphae. The patient was diagnosed with GPP and oral candidiasis in the setting …


Laser And Light-Based Therapy For Hair Growth And Hair Removal, Michelle Wiryadana, Nelva Karmila Jusuf Dec 2025

Laser And Light-Based Therapy For Hair Growth And Hair Removal, Michelle Wiryadana, Nelva Karmila Jusuf

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Recent advances in laser and light-based technologies have introduced new options for both the stimulation of hair growth for alopecia and the reduction of unwanted hair growth. However, the clinical evidence remains varied, and treatment outcomes are influenced by factors such as device type, wavelength, and individual response. Ongoing evaluation of safety, efficacy, and standardization of treatment parameters is therefore essential.

Discussion: This review provides an in-depth discussion of the principles, mechanisms, safety, and efficacy of lasers in promoting hair growth, as well as on lasers and light-based therapies used for hair removal. The mechanisms of laser-induced hair growth …


Evaluating The Impact Of A Community-Based Prostate Cancer Screening Program, Amy Leader, Kristine Pham, Nicola Cianci, Hannah Knapp, Fatuma Doka, Suzanne Barron, Oleksandr Kolesnikov, Jordan Dehoratius, Katie Bradley, Le'ann Robles, Robert Giamboy, Olivia Dahlgren, Leonard G. Gomella Dec 2025

Evaluating The Impact Of A Community-Based Prostate Cancer Screening Program, Amy Leader, Kristine Pham, Nicola Cianci, Hannah Knapp, Fatuma Doka, Suzanne Barron, Oleksandr Kolesnikov, Jordan Dehoratius, Katie Bradley, Le'ann Robles, Robert Giamboy, Olivia Dahlgren, Leonard G. Gomella

Kimmel Cancer Center Faculty Papers

BACKGROUND: One out of eight men in the U.S. will be diagnosed with prostate cancer during his lifetime. Black men are more likely to be diagnosed with and die from prostate cancer than other males, contributing to significant prostate cancer disparities. Early detection, often by routine screening, allows for more options for treatment and an increased chance of survival. Barriers to screening contribute to prostate cancer disparities, particularly among those who lack regular access to health care. Community based screening programs may overcome barriers to prostate cancer screening.

METHODS: An urban, NCI-designated cancer center collaborated with a national prostate cancer …


Effectiveness And Safety Of Moisturizing Wash And Cream In The Treatment Of Elderly Xerosis Cutis, Lili Legiawati, Shannaz Nadia Yusharyahya, Rinadewi Astriningrum, Fathirah Rahmatiah Puteri, Nabila Chalisya Ilyas Dec 2025

Effectiveness And Safety Of Moisturizing Wash And Cream In The Treatment Of Elderly Xerosis Cutis, Lili Legiawati, Shannaz Nadia Yusharyahya, Rinadewi Astriningrum, Fathirah Rahmatiah Puteri, Nabila Chalisya Ilyas

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: The skin undergoes degenerative and metabolic changes with aging, increasing susceptibility to dermatological conditions. Xerosis cutis, characterized by rough, scaly skin on the lower legs, is the most common cause of pruritus in elderly patients, with a prevalence of 38–85%. Treating xerosis cutis is challenging due to its multifactorial causes, especially in the elderly. Moisturizers remain the primary and most effective treatment, providing convenience and efficacy. This study aimed to evaluate the effects of QV Intensive Moisturizing Cleanser™️ and QV Intensive Cream™️ (Ego Pharmaceuticals, Australia), which contain humectants, emollients, and occlusives.

Case Illustration: This observational case series involved six …


Cd177+ Neutrophils: New Drivers Of Liver Regeneration, Yankai Wen, Cynthia Ju Dec 2025

Cd177+ Neutrophils: New Drivers Of Liver Regeneration, Yankai Wen, Cynthia Ju

Faculty, Staff and Student Publications

No abstract provided.


Coordinated Changes In Stromal And Hematopoietic Cells That Define The Perinatal To Juvenile Transition In The Mouse Thymus, Anusha Vasudev, Colin R Moore, Aparna Calindi, Seung Woo Kang, Bryan R Helm, Jayashree Srinivasan, Siddhartha Shah, Erin Baker, Ruiting Zong, Nandini Singarapu, Scott Casey, Andrew N Macintyre, Ken S Lau, Laura P Hale, Qi Liu, Nancy R Manley, Lauren I R Ehrlich, Ellen R Richie Dec 2025

Coordinated Changes In Stromal And Hematopoietic Cells That Define The Perinatal To Juvenile Transition In The Mouse Thymus, Anusha Vasudev, Colin R Moore, Aparna Calindi, Seung Woo Kang, Bryan R Helm, Jayashree Srinivasan, Siddhartha Shah, Erin Baker, Ruiting Zong, Nandini Singarapu, Scott Casey, Andrew N Macintyre, Ken S Lau, Laura P Hale, Qi Liu, Nancy R Manley, Lauren I R Ehrlich, Ellen R Richie

Faculty, Staff and Student Publications

Perinatal T cells have distinctive phenotypes and functions that may be due in part to age-associated features of stromal cells in the perinatal thymus. We identify age-associated changes in mouse thymic epithelial cells, mesenchyme, endothelium, and hematopoietic antigen-presenting cells from birth to one month of age using single-cell transcriptional profiling, flow cytometry, and imaging. Coordinated cellular and molecular changes occur at 7-14 days of age, designated "transitional ages," as thymus growth switches to homeostasis. E2F target gene expression declines, and the expression of type I interferon response genes increases across diverse cell types at transitional ages. Alterations in thymic stromal …


Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes Dec 2025

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …


Pepquerymhc: Rapid And Comprehensive Tumor Antigen Prioritization From Immunopeptidomics Data, Seunghyuk Choi, Bing Zhang Dec 2025

Pepquerymhc: Rapid And Comprehensive Tumor Antigen Prioritization From Immunopeptidomics Data, Seunghyuk Choi, Bing Zhang

Faculty, Staff and Students Publications

Determining tumor-specificity of MHC-bound peptides is crucial for cancer immunotherapy development, yet current methods struggle with class II peptides and non-reference sequences. We introduce PepQueryMHC, an ultra-fast tool that integrates MHC-bound peptide sequences with translated RNA-seq reads for efficient tumor antigen prioritization. We demonstrate its versatility in prioritizing class I and II tumor antigens, mapping the cellular origins of presented peptides, and resolving uncertainties surrounding the prevalence of proteasome-spliced peptides.


Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee Dec 2025

Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee

Faculty, Staff and Students Publications

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis, effects that are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia-inducible factors (HIFs). However, translational effects in hypoxia, which likely precede transcriptional effects, have remained largely unexplored. Using ribosome profiling, we uncovered a selective translational response in acute hypoxia that is eukaryotic initiation factor (eIF)3d/eIF3e dependent and controls downstream hypoxic responses, including HIF1α accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e and eIF3d expression signatures are associated with worsened outcomes for patients with breast cancer. Finally, we identified …


A Tissue Renewal-Based Mechanism Drives Colon Tumorigenesis, Ryan M. Boman, Gilberto Schleiniger, Christopher Raymond, Juan P. Palazzo, Anne Shehab, Bruce M. Boman Dec 2025

A Tissue Renewal-Based Mechanism Drives Colon Tumorigenesis, Ryan M. Boman, Gilberto Schleiniger, Christopher Raymond, Juan P. Palazzo, Anne Shehab, Bruce M. Boman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Our Goal is to identify how colorectal cancer (CRC) arises in the single-layered cell epithelium (simple columnar epithelium) that lines the luminal surface of the large intestine. Background: We recently reported that the dynamic organization of cells in colonic epithelium is encoded by five biological rules and conjectured that colon tumorigenesis involves an autocatalytic tissue renewal reaction. Introduction Our objective was to define how altered crypt turnover explains tissue disorganization that leads to adenoma morphogenesis and CRC. Hypothesis: Changes in rate of tissue renewal-based cell polymerization leads to epithelial expansion and tissue disorganization during adenoma histogenesis. Methods: Accordingly, we created …


Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel Dec 2025

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …


Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu Dec 2025

Epcam Activates The Erk-Egr1 Signaling Axis And Promotes Tnf-Α-Induced The Progression Of Anaplastic Thyroid Cancer, Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y Lai, Han-Chung Wu

Faculty, Staff and Student Publications

Background: Epithelial cell adhesion molecule (EpCAM) is a pleotropic transmembrane glycoprotein comprising an extracellular domain (EpEX), a single transmembrane domain, and an intracellular domain (EpICD). For several types of cancer, high EpCAM expression is associated with tumor progression, metastasis, immune evasion, and overall poor prognosis. A rare but aggressive form of thyroid cancer, anaplastic thyroid cancer (ATC), has a mean survival time of only 3–6 months after diagnosis.

Methods: The levels of EpEX and EpICD cleavage in clinical patient samples was evaluated by using tissue microarray. Capture enzyme-linked immunosorbent assay (ELISA) was conducted to explore the of shedding EpEX and …


Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan Dec 2025

Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan

School of Graduate Studies Faculty Publications

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …


Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko Dec 2025

Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, a member of the AP-1 family of transcription factors, mediates long-term neuroadaptations underlying drug addiction, seizure-related cognitive decline, dyskinesias, and several other chronic conditions. AP-1 transcription factors are notoriously difficult to modulate pharmacologically due to the absence of well-defined binding pockets. Here, we identify a novel site on ΔFOSB, located outside the DNA-binding cleft, that accommodates small molecules. We show that sulfonic acid-containing compounds bind to this site via an induced-fit mechanism, reorienting side chains critical for DNA binding, and that they may hinder the ΔFOSB bZIP α-helix from binding to the major groove of DNA. In vivo, direct …


Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube Dec 2025

Society For Immunotherapy Of Cancer: Standards For Reporting Of Multiplex Immunohistochemistry/Immunofluorescence Assays (Stormi), Sam Sater, Carlo B Bifulco, Jaime Rodriguez-Canales, Joe Yeong, Guray Akturk, Michael Angelo, Carmen Ballesteros-Merino, Peter Bankhead, Subham Basu, Jorge M Blando, Saska Brajkovic, Marco Cassano, Benjamin J Chen, Ahmet F Coskun, Tricia R Cottrell, Carlos E De Andrea, Robin H Edwards, Colt Egelston, Logan L Engle, Marc S Ernstoff, Rong Fan, Michael Feldman, Bernard A Fox, Jerome Galon, Robyn Gartrell, Sacha Gnjatic, Benjamin F Green, James L Gulley, Anne Hellebust, Stephen Hewitt, Travis J Hollmann, Lucas A Horn, William J Howat, Clifford C Hoyt, Shawn M Jensen, Arutha Kulasinghe, Wiem Lassoued, Steven Lott, James Mansfield, Sebastian Marwitz, George Netto, David B Page, Edwin Parra, David L Rimm, Scott J Rodig, Roberto Salgado, Denis Schapiro, Kurt A Schalper, Joel C Sunshine, Michael J Surace, Alexander S Szalay, Magdalena Thurin, Jose C Villasboas, Keith Wharton, Ignacio I Wistuba, Jennifer H Yearley, Yinyin Yuan, Geroge Zaki, James Ziai, Janis M Taube

Faculty, Staff and Student Publications

Multiplex immunofluorescence and immunohistochemistry (mIF/IHC) are increasingly employed antibody-based technologies that use tissue sparingly and facilitate the detection of co-localized or neighboring biomarkers. Specifically, these platforms enable spatial analyses of the tumor microenvironment as well as extended applications, for example, describing normal tissue anatomy, autoimmunity, infectious diseases, etc. mIF/IHC has greatly enhanced biomarker discovery efforts, and a growing number of studies suggest superiority to traditional IHC. Standardization of staining approaches, reporting of image analysis strategies and resultant data is critical for facilitating cross-study comparisons, validation, deployment, and generalization of findings. To address this challenge, The Society for Immunotherapy of Cancer …


Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li Dec 2025

Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li

Faculty, Staff and Student Publications

Sensory processing varies across individuals, with some traits-particularly sensory hypersensitivity to basic non-valenced stimuli-linked to emotional traits and psychiatric risk. Traditional accounts attribute this sensory-emotion linkage to limbic or prefrontal modulation, but empirical support is limited. Growing evidence suggests sensory cortex itself flexibly encodes value beyond labeled-line analysis. Across four high-density EEG experiments with multi-wave assessments, we identified reliable visual cortical hyperactivity in high trait anxiety. The effect emerged as early as 46 ms, localized to V1/V2, and was specific to the parvocellular pathway. It was reproducible across arousal states, stimulus valence, extended intervals, and paradigms, and evident for both …


Peripheral Blood Biomarkers For Rheumatoid Arthritis-Associated Interstitial Lung Disease, Brent A. Luedders Dec 2025

Peripheral Blood Biomarkers For Rheumatoid Arthritis-Associated Interstitial Lung Disease, Brent A. Luedders

Theses & Dissertations

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular complication of rheumatoid arthritis (RA). Measuring peripheral blood biomarkers represents an appealing strategy to inform the screening and prediction of RA-ILD. In these studies, I aimed to further characterize the associations of peripheral blood biomarkers with prevalent and incident RA-ILD. First, I evaluated the associations of matrix metalloproteinases (MMPs) with RA-ILD among a multicenter cohort of RA U.S. Veteran patients (n = 2,312). Higher concentrations of MMP-7 and MMP-9 were independently associated with both prevalent and incident RA-ILD, including a nearly four-fold increased odds of prevalent RA-ILD (adjusted odds ratio …


Protocol For Nucleo-Cytoplasmic Fractionation Of Mammalian Cells To Study Protein Translocation Via Immunoblotting, Adhikarimayum Lakhikumar Sharma, Eddy Zhu, Rithika Padyala, Kavya Parikh, Mudit Tyagi Dec 2025

Protocol For Nucleo-Cytoplasmic Fractionation Of Mammalian Cells To Study Protein Translocation Via Immunoblotting, Adhikarimayum Lakhikumar Sharma, Eddy Zhu, Rithika Padyala, Kavya Parikh, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Studying protein translocation is essential for understanding protein function and regulatory mechanisms, including the activity of transcription factors. Here, we present a protocol for isolating high-quality cytoplasmic and nuclear protein fractions from mammalian cells. We describe steps for separating cytoplasmic proteins, washing nuclei, and extracting nuclear proteins. We then detail procedures for quantifying proteins and analyzing their distribution by immunoblotting within a single immunoblot. This protocol is applicable to both suspension and adherent cell types. For complete details on the use and execution of this protocol, please refer to Sharma et al.


P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold Dec 2025

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …


Beyond Precision: Ambiomic Survivorship In Childhood And Aya Cancer., Juan Antonio Ortega-García, Omar Shakeel, Nicole Wood, Antonio Pérez-Martínez, Jose Luís Fuster-Soler, Mark D. Miller Dec 2025

Beyond Precision: Ambiomic Survivorship In Childhood And Aya Cancer., Juan Antonio Ortega-García, Omar Shakeel, Nicole Wood, Antonio Pérez-Martínez, Jose Luís Fuster-Soler, Mark D. Miller

Manuscripts, Articles, Book Chapters and Other Papers

Background: Survival among children and adolescents and young adults (AYA) with cancer has improved substantially over recent decades; however, dominant survivorship models remain reactive-activated post-treatment and anchored to static exposure- and organ-based screening. This design underuses the anticipatory window at diagnosis and overlooks environmental and social determinants that modulate outcomes across the life course. Methods: We narratively reviewed international frameworks including the Children's Oncology Group (COG), the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG), the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer (PanCare) and the National Comprehensive Cancer Network (NCCN), and synthesized evidence …


Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller Dec 2025

Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller

Faculty, Staff and Students Publications

Adaptive neuromodulation systems and implantable brain-computer interfaces have made notable strides in recent years, translating experimental prototypes into clinical applications and garnering substantial attention from the public. This surge in interest is accompanied by increased scrutiny related to the safety, efficacy, and ethical implications of these systems, all of which must be directly addressed as we introduce new neurotechnologies. In response, we have synthesized the insights resulting from discussions between groups of experts in the field and summarized them into five key domains essential to therapeutic device development: (1) analyzing current landscape of neuromodulation devices and translational platforms (2) identifying …


Transposable Element-Derived Mir-28-5p And Mir-708-5p: Exploring Potential Roles In Lung Cancer, Sergiu Chira, Cornelia Braicu, Stefan Strilciuc, George A Calin, Ioana Berindan-Neagoe Dec 2025

Transposable Element-Derived Mir-28-5p And Mir-708-5p: Exploring Potential Roles In Lung Cancer, Sergiu Chira, Cornelia Braicu, Stefan Strilciuc, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses.

Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. …