Digital Commons Network^™

Immunogenicity And Efficacy Of A Rabies-Based Vaccine Against Highly Pathogenic Influenza H5n1 Virus, Nir Paran, Christoph Wirblich, Randy Albrecht, Leila Zabihi Diba, Alessandro Tarquinio, Drishya Kurup, Charalambos C. Solomides, Adolfo García-Sastre, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV …

Amyloidosis Of Bridging Veins Is A Pathologic Feature Of Alzheimer's Disease, Leon C D Smyth, Daan Verhaege, Elio Standen-Bloom, Yue Wu, Steffen E Storck, Pavle Boskovic, Benjamin A Plog, Tornike Mamuladze, Jose A Mazzitelli, Zhuoying Wang, Daniel D Lee, Gwendalyn J Randolph, Katherine E Schwetye, Song Hu, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by the accumulation of extracellular aggregated amyloid beta, resulting from impaired waste clearance. We recently identified new cerebrospinal fluid (CSF) efflux structures termed arachnoid cuff exit (ACE) points and speculated that these may be impacted in AD, leading to impaired waste clearance function. Using 5XFAD mice, we found progressive amyloidosis of bridging veins at ACE points. Indeed, in 5XFAD mice, there is impaired CSF efflux to the dura mater, impaired CSF flow along bridging veins, and impaired blood flow through bridging veins. These observations suggest that ACE point amyloidosis plays a role in waste clearance …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach., Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary Churchill, David B Allison

Faculty Research 2026

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach., Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary Churchill, David B Allison

Faculty Research 2026

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Somatic Deficiency Of The Human E3 Ubiquitin Ligase Cbl In Leukocytes Impairs B Cell But Not T Cell Development And Function., Taja Vatovec, Anna-Lena Neehus, Katherine J L Jackson, Danielle T Avery, Ivan Bagarić, Lucia Erazo, Carlos A Arango-Franco, Masato Ogishi, Syed F Ahmed, Axel Cederholm, Amanda J Russell, Erika Della Mina, Dena Al-Rifai, Rowena Bull, Lori Buetow, Steicy Sobrino, Allison Zhang, Lara Wahlster, Marine Michelet, Nima Parvaneh, Jessica Peel, Federica Barzaghi, Davide Leardini, Quentin Philippot, Francesco Saettini, Jacques Dutrieux, Benedicte De Muylder, Francesca Vendemini, Francesco Baccelli, Albert Catala, Eleonora Gambineri, Marinella Veltroni, Vignesh Pandiarajan, Yurena Aguilar, Filomeen Haerynck, Michael Elliott, Stuart Turville, Fabienne Brillot, Taushif Khan, Filippo Consonni, Laureline Berteloot, William A Sewell, Geetha Rao, Laetitia Largeaud, Francesca Conti, Cecile Roullion, Cécile Masson, Francesco Pegoraro, Tianyi Ye, Samantha Joubran, Emily Villalpando, Boris Bessot, Yoann Seeleuthner, Tom Le Voyer, Jérémie Rosain, Hailun Li, Zarah Janda, Edoardo Muratore, Camille Soudée, Eric Delabesse, Claire Goulvestre, Mohammad Shahrooei, Anne Puel, Isabelle André, Christine Bole-Feysot, Laurent Abel, Miriam Erlacher, Vivien Béziat, Chantal Lagresle-Peyrou, Remi Cheynier, Emmanuelle Six, Nico Marr, Marlène Pasquet, Laia Alsina, Christopher C Goodnow, Nils Landegren, Alessandro Aiuti, Peng Zhang, Riccardo Masetti, Danny T Huang, Cindy S Ma, Jean-Laurent Casanova, Vijay G Sankaran, Jacinta Bustamante, Stuart G Tangye, Jonathan Bohlen

Faculty Research 2026

The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis …

Divergent Humoral Immune Signatures In Response To Klebsiella Pneumoniae Bacteremia, Paeton L Wantuch, Nadia Wattad, David A Rosen

2020-Current year OA Pubs

OBJECTIVES: Klebsiella pneumoniae is an increasingly threatening global pathogen with high rates of antibiotic resistance and no licensed vaccines available. Despite its worldwide importance, little is known about the human adaptive immune response to K. pneumoniae infection.

METHODS: Herein we observed the longitudinal antibody responses of three immunocompetent patients hospitalized with K. pneumoniae bacteremia. We analyzed the human serum for antibody titers and in vitro functionality. Further, serum function was evaluated via an in vivo mouse model.

RESULTS: We found that in each case, anti-K. pneumoniae antibodies against the infecting strain were still detectable a year after the initial infection. …

Genetic Architecture Of N-Terminal Pro-B-Type Natriuretic Peptide In A Multiancestry Study Population, Naman S Shetty, Akhil Pampana, Mokshad Gaonkar, Amrita Nayak, Harshvir S Bal, Nirav Patel, Nehal Vekariya, J Gustav Smith, Alanna C Morrison, Bing Yu, Bruce M Psaty, Eric Boerwinkle, James S Floyd, Jerome I Rotter, Kent D Taylor, Leslie A Lange, Marguerite R Irvin, Mary Cushman, Stephen S Rich, Ramachandran S Vasan, Thomas J Wang, Xiuqing Guo, Peng Li, Garima Arora, Pankaj Arora

Faculty, Staff and Student Publications

Background: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population.

Methods: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

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 …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Investigating The Oxygen Dependence Of Flash-Rt Using Electron Paramagnetic Resonance Imaging, Trey Waldrop, Grace Murley, Brett Velasquez, Elise Konradsson, Denae Neill, Luke Connell, Alan Lopez Hernandez, Abagail Delahoussaye, F William Schuler, Jorge De La Cerda, Ziyi Li, Mark D Pagel, Emil Schüler

Faculty, Staff and Student Publications

Purpose: The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.

Methods: pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)- noninvasive oximetry through spin probe injection and magnetic resonance co-registration- and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor …

Hyperglycemia, Receptor For Advanced Glycation End Products, And Small Airways Dysfunction In Asthma, Paula Sierra Salas, Dennis T Villareal, Vickram Tejwani, Amrit Koirala, Cristian Coarfa, Meredith C Mccormack, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Background: Diabetes and insulin resistance are associated with higher risk of asthma exacerbation and preserved ratio impaired spirometry (PRISm), but the pathophysiology is unclear. These conditions may cause small airways dysfunction (SAD), which is an under-recognized cause of PRISm.

Objective: To determine whether insulin resistance and poor glucose control associate with SAD and to explore whether proteins prognostic of diabetes end-organ complications predict lung function abnormalities.

Methods: We recruited a prospective cohort of adults with physician-diagnosed asthma. Fasting insulin, glucose, hemoglobin A1c, and concentrations of 13 proteins prognostic of diabetes end-organ complications were measured. Static insulin resistance was calculated by …

13 C-Spirulina Gastric Emptying Breath Test Normative Values In Healthy Children: A Multicenter Study With Comparison To Symptomatic Children, Katja Karrento, Bruno P Chumpitazi, Liyun Zhang, Pippa Simpson, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Diagnosing pediatric gastroparesis presents a significant challenge due to lack of normative data in children. We aimed to determine normative values for gastric emptying using the nonradioactive 13 C-Spirulina gastric emptying breath test ( 13 C-GEBT) in a large cohort of healthy children (HC) and examine differences compared to children with gastroparesis-like symptoms (GLS).

Methods: A total of 301 HC ages 7-18 years completed the 13 C-GEBT with 10 different breath samples × 4 hours. 13 CO 2 excretion rate (kPCD) was determined by change in 13 CO 2 / 12 CO 2 . Outcome variables included: kPCD at …

Maternal Myo-Inositol Intake And Congenital Heart Defects In Offspring: A Population-Based Case-Control Study, Ruiqi Cen, L Joseph Su, Jun Ying, Mohammed S Orloff, Elijah H Bolin, Xiangyang Lou, Lynn M Almli, Lorenzo D Botto, Marilyn L Browne, Richard H Finnell, Mary M Jenkins, Eirini Nestoridi, Andrew F Olshan, Paul A Romitti, Gary M Shaw, Wendy N Nembhard

Faculty, Staff and Students Publications

Objective: To investigate associations between maternal periconceptional (three months prior through the third pregnancy month) myo-inositol intake and the odds of selected congenital heart defects in offspring.

Design: A population-based case-control study using the National Birth Defects Prevention Study (NBDPS) database.

Setting: United States.

Population or sample: Women with singleton live births without major birth defects (controls) and women with singleton live births, stillbirths, or terminations with selected nonsyndromic congenital heart defects (CHD; cases).

Methods: Descriptive analyses, logistic regression models, ascertainment of myo-inositol intake from supplements and food using a shortened food frequency questionnaire and survey.

Main outcome measures: Odds …

Baseline Characteristics In The Synchronize™-2 Randomized Phase 3 Trial Of Survodutide, A Glucagon Receptor/Glp-1 Receptor Dual Agonist, For Obesity In People With Type 2 Diabetes, Sean Wharton, Carel W Le Roux, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide is an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist that has shown promise for treating obesity and its complications in Phase 2 trials. Two double-blind, randomized, global Phase 3 trials are designed to assess the efficacy and safety of survodutide for treatment of obesity-SYNCHRONIZE™-1 in people with obesity without type 2 diabetes (T2D) and SYNCHRONIZE™-2 in people with obesity and T2D. This paper describes the baseline characteristics of participants in SYNCHRONIZE-2 (ClinicalTrials.gov identifier NCT06066528).

Materials and methods: Participants aged ≥18 years with a body mass index (BMI) ≥27 kg/m2 and T2D were randomized 1:1:1 to weekly subcutaneous …

Dolichocolon Is Common In Pediatric Gastroenterology Patients With Constipation And Associated Complaints, David Simon, Donovan Berens, Raul Zambrana Valenzuela, Arvind Mohan, Partha Chakraborty, Timot Kellermayer, Eric H Chiou, Craig L Jensen, Ricardo A Arbizu, Marla B K Sammer, Richard Kellermayer

Faculty, Staff and Students Publications

Objectives: Dolichocolon (DC), classified under International Classification of Diseases, Tenth Revision (ICD-10) code Q43.8 ("Other specified congenital malformations of intestine"), refers to an elongated or redundant large intestine. Recent studies in adults indicate a role for dolichocolon in constipation and disorders of gut-brain interaction. Contrast enema (CE) imaging is commonly used to identify DC, typically defined as a sigmoid colon extending above, or a transverse colon descending below, the iliac crest line. Despite its potential relevance, the prevalence and clinical significance of DC in pediatric gastroenterology remain poorly understood.

Methods: This retrospective study assessed the prevalence of DC in pediatric …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Progressive Neuroinflammation And Deficits In Motor Function In A Mouse Model With An Epg5 Pathogenic Variant Of Vici Syndrome., Bradley Thornton, Alexandra G. Hardinger, Laramie Pence, Priyanka Prem Kumar, Nikolas Connolly, Scott J. Weir, Jay L. Vivian

Manuscripts, Articles, Book Chapters and Other Papers

Vici syndrome (VS) is a rare pediatric genetic disorder characterized by profound developmental delay, seizures, immune deficits, cardiomyopathy and progressive motor dysfunction. This devastating condition is caused by pathogenic variants in the EPG5 gene, which encodes a regulator of autophagy, leading to the accumulation of toxic intracellular material and widespread cellular dysfunction. Less-severe EPG5 pathogenic variants have recently been linked to rare familial forms of Parkinson's disease, suggesting deficits in EPG5 function drive a range of neurodegenerative disorders. Currently, there are no effective treatments for any disorders associated with pathogenic variants of EPG5. The underlying cellular mechanisms driving the progressive …

Sequential Platinum And Parp Inhibition Enhances Pd1 Immunotherapy Efficacy In Murine Brca2 Mutated Pancreatic Cancer, John C Mcvey, Max M Wattenberg, Heather Coho, Kayjana Infante, Kelly Markowitz, Devora Delman, Cynthia Clendenin, Emma E Furth, Rashmi Tondon, Ben Z Stanger, Robert H Vonderheide, Kim A Reiss, Gregory L Beatty

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

Mast Cells Promote Pathology And Susceptibility In Tuberculosis, Ananya Gupta, Vibha Taneja, Javier Rangel-Moreno, Nilofer Naqvi, Abhimanyu, Yun Tao, Mushtaq Ahmed, Kuldeep Singh Chauhan, Daniela Trejo-Ponce De Leon, Gustavo Ramírez-Martínez, Luis Jiménez-Alvarez, Cesar Luna-Rivero, Joaquin Zuniga, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the bacterium

Stat-Independent Functions Of Janus Kinases 1 And 2 Are Obligatory For The Postnatal Development Of Mammary Epithelial Ducts, Rayane Dennaoui, Madison N. Wicker, Carson Moen, Michaela Schlederer, Kerry Vistisen, Aleata A. Triplett, Thomas Rülicke, Hallgeir Rui, Lukas Kenner, Emilio Casanova, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation …

Cxcr4 Induces Memory Formation Over Exhaustion In Car-T Cells To Achieve Durable Leukemia Targeting., Ari Itoh-Nakadai, Minggao Liang, Michiho Shindo, Chen Bibi, Mariko Tomizawa-Murasawa, Saera Fujiki, Akiko Kaneko, Emi Kanamaru, Mari Hashimoto, Hiroshi Kajita, Yoshinari Ando, Miki Kojima, Jonathan Moody, Makoto Iwasaki, Shinsuke Takagi, Ryo Nakagawa, Saumya Agrawal, Hanae Amitani-Iijima, Kaori Sato, Yuriko Sorimachi, Nahoko Suzuki, Takehiro Fukami, Kazuharu Hanada, Satoshi Morita, Kazushige Katsura, Takehisa Matsumoto, Maiko Kobayashi, Masahiko Kato, Yasuyuki Negishi, Mikako Shirouzu, Yuho Najima, Keiyo Takubo, Chung Chau Hon, Naoyuki Uchida, Shuichi Taniguchi, Yukihide Momozawa, Piero Carninci, Leonard D. Shultz, Yoriko Saito, Michiel De Hoon, Jay W Shin, Fumihiko Ishikawa

Faculty Research 2026

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic activity in patient-derived xenograft models. Using single-cell profiling and metabolic analysis, we find that …

Ai-Enabled Ecg Analysis Improves Diagnostic Accuracy And Reduces False Stemi Activations: A Multicenter U.S. Registry, Robert Herman, Bryn E Mumma, Jake D Hoyne, Benjamin L Cooper, Nils P Johnson, Timea Kisova, Anthony Demolder, Adam Rafajdus, Andrej Iring, Timotej Palus, Marta Belmonte, Emanuele Barbato, Suzanne J Baron, Robert Hatala, Stephen W Smith, H Pendell Meyers, Scott W Sharkey, Jozef Bartunek, Timothy D Henry

Faculty, Staff and Student Publications

Background: Timely reperfusion is critical in reducing mortality in ST-segment elevation myocardial infarction (STEMI). Although electrocardiography-guided cardiac catheterization laboratory (CCL) activation on the basis of first medical contact recognition improves system-level response, diagnostic uncertainty, particularly in atypical presentations, contributes to false positive activations (FPAs) and reperfusion delays.

Objectives: The aim of this study was to evaluate the diagnostic performance and operational impact of artificial intelligence (AI)-based electrocardiographic (ECG) analysis in real-world STEMI triage across a multicenter U.S. registry.

Methods: A total of 1,032 patients with suspected STEMI who triggered emergent CCL activation at 3 geographically diverse percutaneous coronary intervention centers …

Creative Arts To Enhance Cervical Cancer Awareness Using Art-Based Messages From A Nigerian Crowdsourcing Open Call: Qualitative Thematic Analysis, Abdulhammed O Babatunde, Olufunto A Olusanya, Peter Kalulu, Temitope Ojo, Onyekachukwu Anikamadu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is a leading cause of cancer deaths among women in Nigeria, yet awareness is low. Historically, art has served as a medium for processing emotions and sharing experiences, which can be effective in promoting health and behavior change.

OBJECTIVE: This study aimed to examine art submissions and social media engagement from a Nigerian crowdsourcing open call to inform co-designed strategies for cervical cancer prevention among women.

METHODS: This study reported following the SRQR (Standard Reporting for Qualitative Research) guideline. From October to November 2023, we launched an open call for art on social media, inviting adult women …

A Universal Of Human Social Cognition: Children From 17 Communities Process Gaze In Similar Ways, Manuel Bohn, Julia Christin Prein, Agnes Ayikoru, Florian M. Bednarski, Ardain Dzabatou, Michael C. Frank, Annette M.E. Henderson, Joan Isabella, Josefine Kalbitz, Patricia Kanngiesser, Dilara Keşşafoğlu, Bahar Köymen, Maira V. Manrique-Hernandez, Shirley Magazi, Lizbeth Mújica-Manrique, Julia Ohlendorf, Damilola Olaoba, Wesley R. Pieters, Sarah Pope-Caldwell, Katie Slocombe, Robert Z. Sparks, Jahnavi Sunderarajan, Wilson Vieira, Zhen Zhang, Yufei Zong, Roman Stengelin, Daniel B.M. Haun

School of Psychology

Theoretical accounts typically assume that key features of human socio-cognitive development are universal. This paper reports a large-scale cross-cultural study (17 communities, diverse ethnicities, N = 1,377, 709 female, mean = 5.50 years, -collected March 2022 to January 2024) on gaze following in early childhood. To test for universality, cognitive processing signatures were derived from a computational model treating gaze following as social vector estimation. Results showed substantial variation between communities and individuals. Yet, the processing signature was found in all communities. Individual differences in performance were related to children's familiarity with the data-collection device but not opportunities for social …

Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models, leading to increased apoptosis and cell cycle arrest. In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated …

Cdk2 Inhibitor Blu-222 Synergizes With Cdk4/6 Inhibitors In Drug Resistant Breast Cancers Through P21/P27 Induction, Linjie Luo, Yan Wang, Tuyen Bui, Xiaoting Jiang, Mei-Kuang Chen, Xiayu Rao, Sepideh Mohammadhosseinpour, Mi Li, Serena Kim, Rachel Y Kim, Saba Kamaliasl, Carmen W Ulizio, Spyros Tsavachidis, Juliana Navarro-Yepes, Nicole M Kettner, Hannah Wingate, Funda Meric-Bernstam, Kelly K Hunt, Jing Wang, Kerrie Faia, Khandan Keyomarsi

Faculty, Staff and Student Publications

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models, leading to increased apoptosis and cell cycle arrest. In vivo, combining BLU-222 with palbociclib or ribociclib produced significant antitumor activity across eight resistant models, driving durable tumor regression and prolonged survival. Mechanistically, BLU-222, alone or with palbociclib, upregulated …

Low Intensity Vibration With Zoledronate Reduces Musculoskeletal Weakness And Adiposity In Estrogen Deprived Female Mice, Gabriel M Pagnotti, Trupti Trivedi, Laura E Wright, Sutha K John, Sreemala Murthy, Ryan R Pattyn, Monte S Willis, Yun She, Sukanya Suresh, Aji F Touray, William R Thompson, Clinton T Rubin, Khalid S Mohammad, Theresa A Guise

Faculty, Staff and Student Publications

Aromatase inhibitors are widely used in the treatment of hormone-sensitive breast cancer, but their suppression of estrogen production accelerates bone loss, increases fracture risk, and negatively impacts muscle and fat metabolism. Here, we demonstrate that daily low intensity vibration, serving as a non-drug mimetic for exercise, protects musculoskeletal health in skeletally immature, female mice under complete estrogen deprivation. Subsequent improvements in vertebral bone density are paralleled by greater and leaner skeletal muscle mass and function alongside reduced fat accretion and circulating metabolites. In mature, estrogen deprived mice, vibration enhances weekly bisphosphonate treatment, improving bone density, cortical thickness, and mechanical resistance …