Digital Commons Network^™

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …

Feasibility And Form Factor Validation Of Reflective Shoulder-Mounted Pulse Oximeter In Patients With Suspected Sleep Apnea, Katie N. Kanter, Aaron Wang, David Gordon, Adina Singer, Jacob S. Brenner, Indira Gurubhagavatula, Anush Lingamoorthy, Olumuyiwa Oni, Cameron M. Baston

SKMC Student Presentations and Publications

The shoulder may be an effective central site for continuous oxygen saturation (SpO2) monitoring but studies of shoulder-mounted pulse oximetry technology are limited. We hypothesized that an alternative location would be similar in function and user acceptance to a standard FDA-cleared finger-based pulse oximeter. We conducted a quantitative and descriptive pilot study of two prototype biosensor designs in patients with clinical suspicion of hypoxic episodes at an outpatient sleep center. Participants wore two prototype biosensors-the primary a shoulder-mounted adhesive and the secondary a combination ring-bracelet-in addition to a control FDA-approved finger-based pulse oximeter. We assessed the comfort of the devices …

Evolving Strategies In Prostate Cancer: Emerging Approaches And Unmet Needs From The Bridging The Gaps In Prostate Cancer Expert Panel, Rana Mckay, Benjamin Maughan, Alicia Morgans, Neal Shore, Evan Yu, Ravi Madan, Jacob Berchuck, Bradley Carthon, Steven Finkelstein, Leonard Gomella, Michael Gorin, Andrew Hahn, Stacy Loeb, Vivek Narayan, Daniel Petrylak, Charles Ryan, Karine Tawagi, Phuoc Tran, Tanya Dorff

Department of Urology Faculty Papers

BACKGROUND: The expansion of treatment options for prostate cancer (PC) has improved disease-specific and overall survival outcomes but has also raised questions about the optimal level of treatment needed for patients based on their individual prognosis and accounting for potential toxicity, incorporating quality of life considerations.

METHODS: A panel of experts met to discuss current controversies in the care of patients with PC across the disease continuum. Multidisciplinary experts review advances and persistent uncertainties in biomarker-guided assessment, imaging, and systemic therapy for prostate cancer. The discussion outlines priority gaps in evidence that must be addressed to optimize individualized patient care. …

Safety Of Carotid Endarterectomy In The Elderly And Octogenarian Population: A Nationwide Study Including 80,000 Patients, Victor Gabriel El-Hajj, Joanna Roy, Basel Musmar, Wi Jin Kim, Michael Rizzuto, Nathaniel Ellens, Rabab Alshahrani, Victor Staartjes, Adrian Elmi-Terander, Ramachandra Tummala, Stavropoula Tjoumakaris, Michael Gooch, Robert Rosenwasswer, Ziad Khabbaz, Pascal Jabbour

Department of Neurosurgery Faculty Papers

INTRODUCTION: Carotid endarterectomy (CEA) is an established procedure for stroke prevention in patients with carotid artery stenosis. While CEA is considered safe in younger patients, perioperative risks in octogenarians remain debated, with current guidelines classifying the procedure as "high-risk" in this patient population. This study aimed to evaluate short-term outcomes of CEA across age groups and to assess whether comorbidity burden better predicts outcomes than chronological age.

METHODS: The ACS-NSQIP database (2013-2020), was used to identify patients eligible for inclusion. The cohort was stratified based on age <  60, 60-80, and > 80 years. Propensity score matching and multivariable logistic regression were used to compare …

Targeting Oxalate Production By Combining Enzyme Inhibition And Proteolysis Activation: A Novel Therapeutic Approach For Primary Hyperoxaluria Type 1, Fabio Arias, Sumati Rohilla, Yudibeth Sixto-López, Koral S E Richard, Sandeep Das, Sumit K Anand, Pilar Maria Luque-Navarro, Guillermo Bañuelos-Sanchez, Juan Luis Pacheco-García, Reethika Gade, M Peyton Mckinney, Dhananjay Kumar, Jemiah Maxie, W Rylan Corr, Nilesh Pandey, Harpreet Kaur, Jibin Ding, Lin Tan, Elisha Scott, Hyung Nam, Eyal Gottlieb, A Wayne Orr, Nirav Dhanesha, Arif Yurdagul, Angel L Pey, Francisco Franco-Montalbán, José A Gómez Vidal, Oren Rom, Mónica Díaz-Gavilán

Faculty, Staff and Student Publications

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by hepatic oxalate overproduction due to alanine-glyoxylate aminotransferase (AGXT) deficiency. Therapeutic strategies targeting glycolate oxidase (GO) and lactate dehydrogenase A (LDHA), key enzymes in glyoxylate metabolism, have shown promise in reducing oxalate burden. However, recently approved siRNA therapies remain limited by high cost, unfavorable pharmacokinetics, and limited global accessibility. We report the development of compound 2, a dual GO/LDHA inhibitor (K i = 390 and 40 nM, respectively) that also promotes hydrophobic tag-mediated autophagic degradation of LDHA. Its efficacy was evaluated in Agxt –/– mice, both in primary …

Community Participatory Co-Design And Development Of A Digital Diabetes Prevention Education Program For Hispanic Families With Obesity: Mixed Methods Study, Sandra Mihail, Marbelly Partida, Lizette Villanueva, Debbe Thompson, Teresia M O'Connor, Salma M Musaad, Maria J Redondo, Erica G Soltero

Children’s Nutrition Research Center Staff Publications

Background: Digital health interventions (DHIs) can extend the reach of disease prevention interventions; however, few are evidence-based, theoretically grounded, or developed for high-risk youth and families. Co-design approaches engage end users in the design and development of the DHI, which can lead to increased accessibility and engagement.

Objective: This study aimed to describe the adaptation of an evidence-based diabetes prevention program for remote, digital delivery.

Methods: The adaptation of the in-person intervention was guided by a modified Inclusive Digital Health Intervention Design to Promote Health Equity framework and conducted in collaboration with Hispanic adolescents (n=23) with obesity (BMI ≥95th percentile) …

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …

Ex Vivo Microfluidic Model Identifies A Role For Shear Stress During Ovarian Tumor Cell Attachment To Peritoneal Mesothelial Cells, Vasilios A Morikis, Breanna Baker, Jillian A Martin, Angela Schab, Alessandra Dimauro, Gregory D Longmore, Whitney R Grither

2020-Current year OA Pubs

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. …

Human Papillomavirus Vaccine Perceptions Among Noncollege Young Adults And Tiktok Influencers: Qualitative Study, Amelia Burke-Garcia, Dasha Afanaseva, Erin Cutroneo, Kayla Madden, Angela Sustaita-Ruiz, Estefany Rivera Sanchez, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Human papillomavirus (HPV) vaccination is a proven and effective tool for preventing several types of cancers, yet vaccination rates among young adults remain suboptimal, particularly among those not enrolled in 4-year colleges. This population can be more difficult to reach due to fewer established institutional touchpoints, limited engagement with campus-based health services, and greater variability in access to preventive care. At the same time, social media has become a dominant source of information for young adults, with TikTok (ByteDance) emerging as one of the most widely used platforms. Approximately 41% of TikTok's users are between the ages of 16 …

Overcoming Host Restrictions To Enable Continuous Passaging Of Gii.3 Human Norovirus In Human Intestinal Enteroids, Gurpreet Kaur, Sue E Crawford, Sara Javornik Cregeen, Anil Surathu, B Vijayalakshmi Ayyar, Carmen V Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E Blutt, Harsha Doddapaneni, Donna M Muzny, Cristian Coarfa, Ramakrishnan Anish, B V Venkataram Prasad, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed …

Targeting Pediatric Glioblastomas By Combining Olig2 Inhibitor Ct-179 With Fractionated Radiation In A Panel Of Patient-Derived Orthotopic Xenograft Mouse Models., Holly Lindsay, Yuchen Du, Lin Qi, Huiyuan Zhang, Sibo Zhao, Frank K Braun, Mari Kogiso, Clifford Stephan, Gordon Alton, Gregory Stein, Graham Beaton, Santosh Kesari, Steven Neuhauser, Timothy M Stearns, Jeffrey Chuang, Emily L Jocoy, Carol J Bult, Beverly Teicher, Malcolm A Smith, Xiao-Nan Li

Faculty Research 2026

The poor clinical outcomes of pediatric high-grade glioma (pHGG) highlight the urgent need for new therapies. Oligodendrocyte lineage transcription factor 2 (OLIG2) is a pro-mitotic transcription factor highly expressed in glioma stem cells and may represent a novel therapeutic target. To evaluate the therapeutic efficacy of an OLIG2 inhibitor CT-179 in pHGG, we determined the OLIG2 mRNA expression in 10 patient-derived orthotopic xenograft (PDOX) models. In vitro activities of CT-179 were analyzed in monolayer and neurosphere cells (0–10 µM) with and without radiation (XRT) (0–8 Gy), brain penetration was evaluated in tumor-bearing PDOX mice, and in vivo efficacy was determined …

Targeting Pediatric Glioblastomas By Combining Olig2 Inhibitor Ct-179 With Fractionated Radiation In A Panel Of Patient-Derived Orthotopic Xenograft Mouse Models., Holly Lindsay, Yuchen Du, Lin Qi, Huiyuan Zhang, Sibo Zhao, Frank K Braun, Mari Kogiso, Clifford Stephan, Gordon Alton, Gregory Stein, Graham Beaton, Santosh Kesari, Steven Neuhauser, Timothy M Stearns, Jeffrey Chuang, Emily L Jocoy, Carol J Bult, Beverly Teicher, Malcolm A Smith, Xiao-Nan Li

Faculty Research 2026

The poor clinical outcomes of pediatric high-grade glioma (pHGG) highlight the urgent need for new therapies. Oligodendrocyte lineage transcription factor 2 (OLIG2) is a pro-mitotic transcription factor highly expressed in glioma stem cells and may represent a novel therapeutic target. To evaluate the therapeutic efficacy of an OLIG2 inhibitor CT-179 in pHGG, we determined the OLIG2 mRNA expression in 10 patient-derived orthotopic xenograft (PDOX) models. In vitro activities of CT-179 were analyzed in monolayer and neurosphere cells (0–10 µM) with and without radiation (XRT) (0–8 Gy), brain penetration was evaluated in tumor-bearing PDOX mice, and in vivo efficacy was determined …

Gene Regulatory Programs Of Nk Cells Show That Ncam1 (Cd56) And Kirs Are Controlled By Genetically Polymorphic Distal Regulatory Elements, Mariam A. Salem, Aditi Varkey, Matthew D. Estrada, Kruthika Sharma, Caprice D. Eisele, Nitin Chakravarti, Dean A. Lee, Aharon G. Freud, Bethany L. Mundy-Bosse, Patrick L. Collins

Kimmel Cancer Center Faculty Papers

Owing to their immunoprotective properties, natural killer (NK) cells are critical for the innate immune response to pathogens, as well as a new wave of cancer immunotherapy that harnesses natural cytotoxicity. We sought to study the genetic and epigenetic drivers behind human-specific NK cell receptors, so that we can better understand the underlying cellular function. Here, we present a transcriptomic, proteomic (CITE-seq), and chromatin (single nuclei ATAC-seq) profiling of human peripheral NK cell subsets, which was then compared with genomic databases. Through integrative multi-omics, we demonstrate that CD56^bright versus CD56^dim NK cell subsets have differential distal regulatory element …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Andrew Massey, Vivek K Kashyap, Neeraj Chauhan, Emmanuel Anning, Manish K Tripathi, Dae J Kim, Nirakar Sahoo, Tamer Oraby, Murali M Yallapu, Mohammad Moshahid Khan, Manu M Sebastian, Subhash C Chauhan, Bilal B Hafeez

Faculty, Staff and Student Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Nci-Designated Cancer Centers' Policies And Practices With Regard To Alcohol And Cancer: A Call To Lead, Ernest T Hawk, Stephanie L Martch, Meghan Si, Sanjay Shete

Faculty, Staff and Student Publications

Background: Alcohol, a known carcinogen since 1988, increases risk of cancers of the mouth, pharynx, larynx, esophagus, liver, breast, and colorectum. More than one half of US adults consume alcohol whereas about two thirds are unsure whether or unaware that alcohol intake is linked to cancer risk.

Methods: Our objective was to survey awareness, beliefs, intentions, policies, practices, and goals/perceived responsibilities related to establishing/promoting actions to reduce alcohol-related cancer risks from leaders of 72 NCI-Designated Cancer Centers.

Results: Sixty-one percent responded. Forty-three percent either believed in or were uncertain about alcohol's purported health benefits. Nevertheless, 86% considered it part of …

Intercalated Bacterial Biofilms Are Intrinsic Internal Components Of Calcium-Based Kidney Stones, William C Schmidt, Henry L Schreiber, Rachael E S Hammann, Chloe L P Obernuefemann, Karla Bergeron, Aleksandra Klim, Daniel Wong, Kefu Du, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Calcium oxalate stones comprise greater than 70% of all kidney stones. In the current conceptual framework, the initial stone nidus is thought to include the aggregation of inorganic crystallites, the formation of which is favored by elevated concentrations of dissolved constituents. Here, we show that this highly prevalent stone type comprises a form of organic-inorganic polycrystalline biocomposite with integrated bacterial biofilms. Evidence from electron microscopy and fluorescence microscopy reveal the unanticipated internal structure of kidney stones from human patients, where bacterial biofilms are intercalated between polycrystalline mineral layers, even in stones identified as "noninfectious" clinically, including those in patients without …

Cd8+ T Cells In The Tumor Microenvironment Modulate The Response To Endocrine Therapy In Breast Cancer, Fabiana Napolitano, Yunguan Wang, Dhivya R Sudhan, Paula I Gonzalez-Ericsson, Luigi Formisano, Nisha Unni, Shahbano Shakeel, James Z Zhu, Khushi Ahuja, Lei Guo, María Rosario Chica-Parrado, Yuki Matsunaga, Pamela Luna, Chang-Ching A Lin, Yasuaki Uemoto, Kyung-Min Lee, Hongli Ma, Nathaniel J Evans, Alberto Servetto, Saurabh Mendiratta, Spencer D Barnes, Roberto Bianco, Yisheng V Fang, Lin Xu, Jeon Lee, Tao Wang, Justin M Balko, Gordon B Mills, Marilyne Labrie, Ariella B Hanker, Carlos L Arteaga

Faculty, Staff and Student Publications

The role of the tumor immune microenvironment (TIME) in modulating responses to antiestrogen therapy in hormone receptor-positive (HR+) breast cancers remains unclear. We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED). Stromal tumor-infiltrating lymphocytes, assessed by H&E staining, and immune-related gene sets, including IFN-γ signaling genes, measured by RNA-Seq, were increased in ED-resistant tumors. Cyclic immunofluorescence and spatial transcriptomics revealed an abundance of CD8+ T cells and enhanced antigen processing and immune gene signatures in ED-resistant tumors. In this group, the expression of CXCL9, CXCL10, and CXCL11 - chemokine …

Osimertinib Activates A Tgf-Β2-Dependent Secretory Program That Drives Lung Adenocarcinoma Progression, Madhurima Ghosh, Chao Wu, Abhishek Kumar, Monique Nilsson, John V Heymach, Weina Zhao, Jiang Yu, Xin Liu, Na Ding, Shike Wang, Guan-Yu Xiao, Angelo Chen, Kate Grimley, William K Russell, Chad J Creighton, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

EGFR-mutant lung adenocarcinomas (LUADs) that are vulnerable to the EGFR antagonist osimertinib (Osi) eventually relapse, owing in part to the emergence of drug-tolerant persister (DTP) cells that arise through epigenetic mechanisms. Intratumoral DTP cells can herald a worse clinical outcome, but the way in which DTP cells influence LUAD progression remains unclear. Osi-resistant (OR) cells exhibit typical DTP cell features, including a propensity to undergo senescence and epithelial-mesenchymal transition (EMT), which can activate heightened secretory states. Therefore, we postulated that OR cells influence LUAD progression through paracrine mechanisms. To test this hypothesis, we utilized congenic pairs of EGFR-mutant LUAD cell …

Estimated Effectiveness Of 2024-2025 Covid-19 Vaccination Against Severe Covid-19, Kevin C Ma, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies.

OBJECTIVE: To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, …

Longitudinal Multiomic Signatures Of Ards And Sepsis Inflammatory Phenotypes Identify Pathways Associated With Mortality, Narges Alipanah-Lechner, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUNDCritically ill patients with acute respiratory distress syndrome (ARDS) and sepsis exhibit distinct inflammatory phenotypes with divergent clinical outcomes, but the underlying molecular mechanisms remain poorly understood. These phenotypes, derived from clinical data and protein biomarkers, were associated with metabolic differences in a pilot study.METHODSWe performed integrative multiomics analysis of blood samples from 160 patients with ARDS in the ROSE trial, randomly selecting 80 patients from each latent class analysis-defined inflammatory phenotype (hyperinflammatory and hypoinflammatory) with phenotype probability greater than 0.9. Untargeted plasma metabolomics and whole-blood transcriptomics at day 0 and day 2 were analyzed using multimodal factor analysis (MEFISTO). …

Nrn1 As A Therapeutic Target For Alzheimer's Disease., Derian A Pugh, Gregory Cary, Kelsey M Greathouse, Lauren C Nassour-Caswell, Emma L Hobby, Nicholas T Seyfried, Jeremy H Herskowitz

Faculty Research 2026

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

METHODS: Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory-Sage-SGC-JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

RESULTS: NRN1 has a TREAT-AD target risk score of 3.29 out of 5. Based on single-nucleus RNA sequencing from SEA-AD, NRN1 expression …

Nrn1 As A Therapeutic Target For Alzheimer's Disease., Derian A Pugh, Gregory Cary, Kelsey M Greathouse, Lauren C Nassour-Caswell, Emma L Hobby, Nicholas T Seyfried, Jeremy H Herskowitz

Faculty Research 2026

INTRODUCTION: Neuritin-1 (NRN1) was identified as a synaptic protein associated with cognitive resilience to Alzheimer's disease (AD).

METHODS: Target risk score and cell type expression profiles were generated for NRN1 using methods developed by the Emory-Sage-SGC-JAX Target Enablement to Accelerate Therapy Development for Alzheimer's Disease (TREAT-AD) Center and Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD). Antibody characterization was conducted using Western blots and densitometry to assess the relative protein abundances of NRN1 in rodents, humans, and cell models.

RESULTS: NRN1 has a TREAT-AD target risk score of 3.29 out of 5. Based on single-nucleus RNA sequencing from SEA-AD, NRN1 expression …

The Long-Term Effectiveness Of The Anti-Obesity Medication Phentermine (Leap) Trial: Rationale, Design, And Baseline Characteristics, Caroline Blackwell Young, Emily Rives, Kimberly A Gudzune, Byron C Jaeger, Courtney G Simmons, Brian N White, Stephanie A Hooker, Deborah B Horn, Deborah R Young, Jennifer Vesely, Amanda Velazquez, Catherine Price, Shelly D Cook, Katy Martin-Fernandez, Galina Inzhakova, Nicholas M Pajewski, Jamy D Ard, Kristina H Lewis

Faculty, Staff and Student Publications

Background: Current clinical practice guidelines support the long-term use of pharmacotherapy for obesity treatment. Historically, phentermine has been one of the most prescribed obesity medications (OMs), however, its long-term efficacy and safety have never been evaluated in a randomized trial as its market approval predates such requirements. Here we describe the design, rationale, and baseline characteristics for a 24-month, double-blind, randomized controlled trial evaluating the efficacy, cardiovascular risk, and safety of phentermine in adults with overweight or obesity.

Methods: This multicenter trial will compare outcomes among participants randomized to phentermine 24 mg daily versus placebo for 24 months. All participants …

Clinical Evaluation Of Nasal Swab Specimens In Vtm/Utm And Respdirect Estm Using The Panther Fusion Sars-Cov-2/Flu A/B/Rsv Assay., Salika M. Shakir, Robert K. Mccall, Rangaraj Selvarangan, Dithi Banerjee, Yitz Goldstein, Christine Lansang, Rachel Bogh, Carmelle V. Remillard, Respdirect Clinical Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory viral infections by SARS-CoV-2, influenza A and B viruses, and RSV overlap in disease signs and symptomology, but differ in treatment modality. Nasal swab specimens have been shown to be an effective alternative specimen type for SARS-CoV-2 detection.

OBJECTIVES: This study evaluated the performance of the Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay in anterior nasal swab specimens (self- or healthcare professional [HCP]-) collected in either viral/universal (VTM/UTM) transport media or the Hologic® RespDirect® collection kit (RespDirect swab in enhanced specimen transport media [eSTM]).

STUDY DESIGN: A multicenter study was conducted from October 2022 to March 2024. A total of …

Species-Dependent Gazing Behavior Of Emotional Facial Expressions In Dogs (Canis Familiaris) And Adult Humans (Homo Sapiens)., Heini Törnqvist, Gray S. Atherton, Liam Cross, Sanni Somppi, Jarkko Hautala, Miiamaaria V. Kujala

School of Psychology

Emotional expressions play an important part in social communication of dogs and humans, but comparative studies between dogs and humans are rare. In addition, little is known about how emotions are perceived across species and how attention is divided among different parts of faces. Here, we compared the gazing behavior of dogs and adult humans toward emotional dog and human facial expressions. Dogs mostly gazed at the eye and nose areas, whereas the humans’ focus also included the mouth area. The gazing behavior of both species was affected by the facial expressions and species presented, and they gazed at emotional …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

A Step-By-Step Guide To Performing Cancer Metabolism Research Using Custom-Made Media, Sophie Seifert, Francisco Yanqui-Rivera, Tim Kühn, Lena Elise Høyland, Toman Borteçen, Bella Agranovich, Lara Elea Eckhardt, Martin Herdt, Alessa Henneberg, Verena Panitz, Faisal Hayat, Marie Migaud, Gernot Poschet, Ifat Abramovich, Eyal Gottlieb, Jeroen Krijgsveld, Mathias Ziegler, Mirja Tamara Prentzell, Christiane A Opitz

Faculty, Staff and Student Publications

The preparation of custom-made media offers precise control over nutrient composition, enabling detailed studies of cellular metabolism. We demonstrate how self-made media formulations enable diverse assay designs and readouts to assess cancer metabolism. Self-made media can be used in Seahorse assays to measure mitochondrial respiration under defined conditions. In nutrient deprivation experiments, amino acid or vitamin removal can uncover how cancer cells adapt to metabolic stress. Using labeled amino acids enables analysis of nascent protein synthesis and translational regulation, while stable-isotope tracing reveals metabolic fluxes through key pathways. This guide presents a suite of metabolic assays using custom-made media, covering …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Apea: A Type 1 Diabetes Self-Management Ambient-Ai Assistance Tool That Bridges Trajectory Prediction, Interactive Explanation, And Just-In-Time Adaptive Intervention Action., Kun-Yi Chen, Erin M. Tallon, Chi-Ren Shyu

Manuscripts, Articles, Book Chapters and Other Papers

Helping patients self-managing diseases like type 1 diabetes (T1D) requires informatics tools delivering real-time predictions with explainable, actionable guidance. However, many healthcare AI solutions lack actionable recommendations and user-friendly explanations, limiting clinical impacts. We introduce APEA, a pediatric T1D self-management Ambient-AI assistance tool, integrating glucose multi-trajectory-scenarios Prediction, interactive, context-aware large language model Explanations, and just-in-time adaptive intervention policy optimization for Actionable real-time suggestions through reinforcement learning. Using T1DEXIP dataset (262 pediatric T1D patients, multi-center), our results showed improved glucose control outcomes: 45% over human management, 69% over infusion-pump management. Although constrained by small sample size and …