Digital Commons Network^™

Whole-Genome Crispr Screening Identifies Genetic Modifiers Of Stem Cell-Derived Islet Transplantation, Marlie M Maestas, Kameron Bradley, Mira Shunkarova, Noyonika Mukherjee, Matthew Ishahak, James Lu, Jeffrey R Millman

2020-Current year OA Pubs

INTRODUCTION: Genetically engineering human pluripotent stem cell (hPSC)-derived islets is a promising strategy for improving transplantation for diabetes cell therapy; however, genetic perturbations that modulate transplantation outcomes have yet to be systematically explored.

METHODS: To identify potential targets, we performed an unbiased whole-genome CRISPR-activation screen in transplanted stem cell-derived islets (SC-islets). Specifically, we created a stem cell line with CRISPR-activation components (HUES8-VPR) and then transduced these stem cells with a lentiviral guide RNA library targeting the whole human genome. Following transduction, the stem cells were differentiated into SC-islets, which were subsequently transplanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) immunodeficient mice. After transplantation, SC-islets …

Therapeutic Plasma Exchange For Uncontrollable Bleeding After Platelet Inhibition With Ticagrelor: A Report Of 2 Cases, Amanda Herrmann, Brenda Mai, Yu Bai, Brian Castillo, Biswajit Kar, Kimberly Klein, Ismael A Salas De Armas, Eric Salazar, Hlaing Tint, Igor D Gregoric

Faculty, Staff and Student Publications

Case series

Patients: Male, 52-year-old Male, 66-year-old

Final Diagnosis: Uncontrolled bleeding following ticagrelor associated with cardiac surgery

Symptoms: Bleeding

Clinical Procedure: —

Specialty: Cardiology Critical Care Medicine Pathology

Objective: Unusual clinical course

Background

Acute coronary syndrome is the most common cause of death in the United States. Successful intervention often requires a multi-therapeutic approach, including percutaneous coronary intervention (PCI) and antiplatelet agents such as ticagrelor. However, the use of antiplatelet agents can cause life-threatening bleeding, particularly during emergency procedures. Therapeutic plasma exchange (TPE) is a procedure that selectively removes the patient’s plasma to eliminate harmful substances. Here, we present 2 …

Eligibility For Amyloid Targeting Therapies Among Primary Care Patients With Cognitive Symptoms, Beata Borgström Bolmsjö, Josef Barbosa Djärf, Danielle Van Westen, Suzanne E Schindler, Ayesha Fawad, Lyduine Collij, Ruben Smith, Niklas Mattsson-Carlgren, Erik Stomrud, Pontus Tideman, Oskar Hansson, Sebastian Palmqvist

2020-Current year OA Pubs

BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia and a growing healthcare challenge. Amyloid-targeting therapies (ATT) may slow progression, but implementation is limited by logistical and economic barriers. As primary care is the first contact for most patients with cognitive concerns, quantifying treatment eligibility in this setting is essential. The purpose of this study was to estimate the proportion of primary care patients presenting with cognitive symptoms who are eligible for ATT. METHODS: This cohort study included patients presenting with cognitive symptoms in primary care across the region Skåne, in southern Sweden, recruited between January 2020 and …

Chatgpt Versus Uptodate In Preclinical Medical Education: Cross-Sectional Analysis Using Term Frequency-Inverse Document Frequency Cosine Similarity, Shankar S. Thiru, Nicholas E. Aksu, Matthew Chiang, Daniel O. Gallagher, Mary Furlong, Elizabeth R. Prevou, Akhil Jay Khanna

Rothman Institute Papers

BACKGROUND: Generative artificial intelligence tools such as ChatGPT are increasingly used by medical students for self-directed learning. Although these models demonstrate linguistic fluency, their reliability as supplementary resources for preclinical education remains uncertain. In particular, comparisons with evidence-based references such as UpToDate are lacking.

OBJECTIVE: This study evaluated the similarity between responses generated by ChatGPT (with GPT-4o mini) and those from UpToDate to preclinical medical education questions to assess ChatGPT's potential as an adjunctive learning tool.

METHODS: We conducted a cross-sectional comparison study using 150 first-order questions derived from a preclinical question bank at a single allopathic institution under the …

Photobiomodulation In Treatment Of Head And Neck Cancer-Related Chronic Lymphedema: A Pilot Randomized Controlled Trial, Jie Deng, John N. Lukens, Barbara A. Murphy, Erin Mcmenamin, Karthik Rajasekaran, Ryan J. Quinn, Joy C. Cohn, Wendy Schlessinger, Lucy P. Andersen, Bryan A. Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

BACKGROUND: Chronic lymphedema is a common late effect after completion of head and neck cancer (HNC) treatment, contributing to substantial symptom burden and negatively impacting quality of life. No effective approaches are available to treat this progressive condition. This study aimed to evaluate the preliminary efficacy of photobiomodulation (PBM) therapy for chronic lymphedema in HNC survivors.

METHODS: This was a pilot, randomized, wait-list controlled trial. Eligible HNC survivors included those with chronic lymphedema after completion of complete decongestive therapy. Participants were randomized (1:1) to 1 of 2 arms: intervention group (active) or wait-list control group (control). The active group received …

Conquering Today's Health Paradox With The Power Of Heal - An Expert Consensus Report Plus Research Priorities And Policymaker Roadmap, Katharina C Wirnitzer, Mohamad Motevalli, Derrick R Tanous, Clemens Drenowatz, Maximilian Moser, Holger Cramer, Thomas Rosemann, Karl-Heinz Wagner, Andreas Michalsen, Beat Knechtle, Zlatko Fras, Adilson Marques, Nataša Fidler Mis, Fatima C Stanford, Christian Schubert, Nandu Goswami, Claus Leitzmann, Per Morten Fredriksen, Gerhard Ruedl, Rodrigo A Lima, Christian Kessler, Michael Jeitler, Naim A Khan, Hassan Joulaei, Maryam Fatemi, Karl W Kratky, Kara K Palmer, Bernd Haditsch, Boštjan Jakše, Walter Kofler

School of Health Professions

BACKGROUND: Despite growing scientific evidence and health guidelines, the global health paradox persists, with rising lifestyle-related diseases and escalating healthcare costs exposing the inadequacy of current efforts.

OBJECTIVE: Three multidisciplinary congresses were held to generate evidence-based conclusions aimed at addressing the global health paradox.

METHODS: A total of 58 experts from 62 entities participated in the international research and knowledge-exchange panels. Experts reviewed the latest findings to develop practical strategies and identify key research and policy priorities, focusing on the Healthy Eating & Active Living (HEAL) approach.

RESULTS CONCLUSION AND RELEVANCE: The expert consortium endorsed a 33 evidence-based consensual-statement policy …

Progress Of Hiv Care Cascade And Transition Dynamics Along The Continuum Of Care Among Persons Living With Hiv In Ifakara, Tanzania: A Prospective Study, Aneth Vedastus Kalinjuma, Aaloke Mody, Tracy Renée Glass, Maja Weisser, Ezekiel Luoga, Honorati Masanja, Fiona Vanobberghen, Kennedy Otwombe

2020-Current year OA Pubs

BACKGROUND: While cross-sectional assessments offer snapshots of care cascade progress, longitudinal analyses are essential to capture the dynamic engagement in care of people living with HIV (PLHIV). We assessed the advancement of the HIV cascade, engagement in care and factors associated with different transitions among PLHIV at the Chronic Disease Clinic of Ifakara, Ifakara, Tanzania, using both cross-sectional and longitudinal analyses. METHODS: In this prospective study, we included PLHIV enrolled in care from 04/2005 to 09/2022 and consented to participate in the Kilombero and Ulanga Antiretroviral Cohort. A cross-sectional care cascade was assessed descriptively. In longitudinal analysis, we used continuous-time, …

Fibrinogen-Bmal1 Signaling As A Therapeutic Target To Limit Aortic Dissection By Preserving Vsmc Contractility, Xiaohan Zhong, Dongjie Li, Yuanfei Zhao, Lu Dai, Jinzhang Li, Zhiqi Ji, Bojing Zuo, Hongshan Liu, Haixia Huang, Wei Wang, Haiyang Li, Yuyong Liu, Ming Gong, Xin-Liang Ma, Wenjian Jiang, Meili Wang, Hongjia Zhang

Department of Emergency Medicine Faculty Papers

Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: …

Pulmonary Complications Of Cancer Therapy: Clinical Presentations, Imaging Patterns, And Management Strategies, Bilal Zafar, Tasmea Haque, Miranda Tan, Ritika Singh, Lara Bashoura, Ajay Sheshadri, Maria Azhar, Saadia A Faiz

Faculty, Staff and Student Publications

Background and objectives: Therapeutic agents for cancer can cause unique pulmonary toxicities and mimic other conditions. The advent of new targeted molecular and immune therapies has changed the landscape of cancer treatment. These adverse events pose diagnostic and therapeutic challenges. This review aims to summarize the clinical presentations, radiographic patterns, and management strategies for noninfectious pulmonary complications associated with cancer therapies.

Materials and methods: A literature review was conducted focusing on drug-induced lung injury (DILI), radiation-induced lung injury (RILI), pleural disease, pulmonary vascular complications, and other inflammatory conditions in patients with cancer. The data sources included clinical trials, guideline recommendations, …

Efficient Multi-Kilobase Knock-Ins In Mice And Cell Lines Using Crispr/Cas9 And Raav Donors With Unbiased Whole-Genome Characterization By Lock-Seq, Monica F Sentmanat, Zi Teng Wang, Evguenia Kouranova, Samuel T Peters, Wan Ching Chan, Jed Lin, Yong Miao, J Michael White, Mia Wallace, Xiaoxia Cui

2020-Current year OA Pubs

Multi-kilobase knock-ins (KIs) are a necessary, yet challenging type of genome editing to create and characterize in cell lines and animals. The combination of rAAV donor transduction and electroporation of single-cell mouse embryos with Cas9/gRNA ribonucleoprotein complex enables highly efficient KI, but the insert size is limited by the viral packaging capacity. Here, we report the creation of up to 6.7 kb precise KI achieved in one step by using three rAAVs designed to insert one after the other. To fully characterize the edited genome with large KIs, we developed LOCK-seq (LOng-read sequencing of Captured Kilo-base targets), where relevant genomic …

Patient Perceptions And Knowledge Of Corticosteroid Injections: A Cross-Sectional Survey Study, Juliet Chung, Sina Ramtin, Philip Koehler, Stephen Stache, Charles Langman, Bryan Hozack, Asif M. Ilyas

Rothman Institute Papers

INTRODUCTION: Although cortisone injections are commonly used, patient understanding of cortisone is variable and often affected by misconceptions. This study explores patient perspectives, identifies misconceptions, and emphasizes the importance of improved patient education to enhance patient-centered care.

METHODS: A cross-sectional survey study was conducted from April to August 2024 among patients aged 18 and older presenting to an orthopedic physicians' office. Patients completed a novel anonymous questionnaire designed to assess their knowledge and perceptions of cortisone injections. A total of 246 patients participated, with responses collected electronically via SurveyMonkey.

RESULTS: Among 246 respondents, individuals with history of prior cortisone infections …

Impact Of Long-Term Nitrogen Scavenger Therapy On Clinical Outcome In Individuals With Urea Cycle Disorders, Roland Posset, Friederike Epp, Sven F Garbade, Florian Gleich, Andrea L Gropman, Sandesh C S Nagamani, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Principles of long-term medical management in individuals with urea cycle disorders (UCDs) encompass (1) a low protein diet, (2) supplementation of arginine and/or citrulline along with essential amino acids, nutrients, vitamins and trace elements, and (3) use of nitrogen scavenging agents to reduce recurrent hyperammonemic events (HAEs). These principles aim at providing metabolic stability, elimimation of chronic complications, and achievement of normal development as well as growth. A retrospective comparative analysis was performed by studying 138 individuals with male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) based on in vitro residual enzymatic activity for severity-adjustment. …

On-Resin Diamsar-Conjugated Cd38-Targeted Peptides And Their Inverso And Dimeric-Inverso Analogs For Pet Imaging Of Multiple Myeloma, Amit Kumar Sharma, Rui Tang, Alexander Zheleznyak, Brad Manion, Erin Teubner, Julie L Prior, Tommy Bauer, Michael Riley Dyer, Stephen Lees, Kimberly Kelly, Monica Shokeen

2020-Current year OA Pubs

CD38 is an established biomarker of multiple myeloma (MM), and peptide-based radiopharmaceuticals targeted to this receptor offer a route to molecularly specific imaging. In this work, we identified a novel CD38-targeted peptide sequence (HAPWFRGGGGS) through phage display and synthesized it using automated solid-phase peptide synthesis. The peptide was modified by introducing a PEG

Polθ Activity Modulates Sensitivity To Standard Therapies In Dnmt3a-Deficient Leukemia, Bac Viet Le, Umeshkumar Vekariya, Monika M. Toma, Margaret Nieborowska-Skorska, Marie-Christine Caron, Malgorzata Gozdecka, Zayd Haydar, Martin Walsh, Jayashri Ghosh, Elaine Vaughan-Williams, Paulina Podszywalow-Bartnicka, Anna-Mariya Kukuyan, Sylwia Ziolkowska, Jessica Atkins, Emir Hadzijusufovic, Gurushankar Chandramouly, Reza Nejati, Katarzyna Piwocka, Richard T. Pomerantz, George S. Vassiliou, Brian J.P. Huntly, Peter Valent, Mariusz Wasik, Alfonso Bellacosa, Jean-Yves Masson, Gaorav P. Gupta, Grant A. Challen, Tomasz Skorski

Department of Biochemistry and Molecular Biology Faculty Papers

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are refractory to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double-strand breaks (DSBs) and stalled replication forks, rendering them dependent on DNA damage response (DDR). We report here that DNA polymerase theta (Polθ), a key element in DSB repair by end-joining (Polθ-mediated end-joining [TMEJ]) and in fork restarting, promotes survival and proliferation of DNMT3Amut leukemia cells. Polθ is overexpressed in DNMT3Amut leukemia cells due to abrogation of PARP1 PARylation-dependent UBE2O E3 ligase-mediated ubiquitination and proteasomal degradation of Polθ. In addition, PARP1-mediated recruitment of the SMARCAD1-MSH2/MSH3 repressive complex to DSBs is diminished in …

Factors Associated With Telemedicine Use By Cardiologists For Medicare Beneficiaries In 2022 To 2023: An Observational Study, Samantha Harris, R J Waken, Fengxian Wang, Khavya C Avula, Rishi K Wadhera, Jose F Figueroa, E John Orav, Uchenna Ofoma, Karen E Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, the Centers for Medicare and Medicaid Services created a waiver to reimburse telemedicine services. It is important to understand factors that facilitate incorporation of telemedicine into ongoing cardiovascular practice.

METHODS: This was a retrospective cohort study of telemedicine and office visits delivered by cardiologists between January 1, 2022, and December 31, 2023, for Medicare beneficiaries. We calculated the adjusted incidence rate ratio (aIRR) of telemedicine visits, representing the proportion of a physician's visits delivered by telemedicine, to identify factors associated with telemedicine use.

RESULTS: There were 23 334 physicians in our cohort; they were predominantly …

Tet Cpg Sequence-Context-Specific Dna Demethylation Shapes Progression Of Idh-Mutant Gliomas., Youri Hoogstrate, Santoesha A Ghisai, Levi Van Hijfte, Rania Head, Iris De Heer, Marta Padovan, Maurice De Wit, Wies R Vallentgoed, Angelo Dipasquale, Maarten M J Wijnenga, Bas Weenink, Rosa Luning, Sybren L N Maas, Adela Brzobohata, Michael Weller, Tobias Weiss, Maximilian J Mair, Anna S Berghoff, Adelheid Wöhrer, Albert Jeltsch, Johan A F Koekkoek, Hans M Hazelbag, Mathilde C M Kouwenhoven, Yongsoo Kim, Bart A Westerman, Bauke Ylstra, Anneke M Niers, Kevin C Johnson, Frederick S Varn, Roel G W Verhaak, Mustafa Khasraw, Martin J Van Den Bent, Pieter Wesseling, Pim J French

Faculty Research 2026

Treatment decisions in IDH-mutant oligodendrogliomas are shaped by tumor aggressiveness, underscoring the need for objective grading of these malignant brain tumors. We collect 302 primary and recurrent resections from oligodendrogliomas and perform Ki-67 staining, proteomics, and DNA methylation profiling. During tumor progression, DNA methylation of oligodendrogliomas changes along a continuum. This continuum is linked to increased epigenetic aging, methylation of transcription factors and Ki-67+ cell density, and large-scale DNA demethylation. Demethylation correlates with CpG flanking sequences preferred by TET enzymes. We confirm these findings in previously profiled astrocytomas, indicating IDH-mutant gliomas progress along a shared epigenetic axis. We develop an …

Tet Cpg Sequence-Context-Specific Dna Demethylation Shapes Progression Of Idh-Mutant Gliomas., Youri Hoogstrate, Santoesha A Ghisai, Levi Van Hijfte, Rania Head, Iris De Heer, Marta Padovan, Maurice De Wit, Wies R Vallentgoed, Angelo Dipasquale, Maarten M J Wijnenga, Bas Weenink, Rosa Luning, Sybren L N Maas, Adela Brzobohata, Michael Weller, Tobias Weiss, Maximilian J Mair, Anna S Berghoff, Adelheid Wöhrer, Albert Jeltsch, Johan A F Koekkoek, Hans M Hazelbag, Mathilde C M Kouwenhoven, Yongsoo Kim, Bart A Westerman, Bauke Ylstra, Anneke M Niers, Kevin C Johnson, Frederick S Varn, Roel G W Verhaak, Mustafa Khasraw, Martin J Van Den Bent, Pieter Wesseling, Pim J French

Faculty Research 2026

Treatment decisions in IDH-mutant oligodendrogliomas are shaped by tumor aggressiveness, underscoring the need for objective grading of these malignant brain tumors. We collect 302 primary and recurrent resections from oligodendrogliomas and perform Ki-67 staining, proteomics, and DNA methylation profiling. During tumor progression, DNA methylation of oligodendrogliomas changes along a continuum. This continuum is linked to increased epigenetic aging, methylation of transcription factors and Ki-67+ cell density, and large-scale DNA demethylation. Demethylation correlates with CpG flanking sequences preferred by TET enzymes. We confirm these findings in previously profiled astrocytomas, indicating IDH-mutant gliomas progress along a shared epigenetic axis. We develop an …

Avian Influenza Preparedness In Ghana: A Cross-Sectional Assessment Of Knowledge, Attitudes, And Practices Among Residents Of Nsawam-Adoagyiri Municipality, Eastern Region, Christopher Yaw Dumevi, George Boateng Kyei, Et Al.

2020-Current year OA Pubs

BACKGROUND: Avian influenza (AI) represents a persistent threat to public health, food security, and livelihoods in Ghana, where outbreaks of H5N1 and H9N2 have occurred. This cross-sectional study evaluated the knowledge, attitudes, and practices (KAP) related to avian influenza among residents of the Nsawam-Adoagyiri Municipality; an area characterized by intensive poultry production with the aim of delineating deficits in community-level preparedness and guiding evidence-based public health interventions. METHODS: A community-based cross-sectional study was conducted from May to July 2025 using a four-stage sampling technique. We surveyed 321 adults via structured questionnaires, evaluating socio-demographics and KAP related to AI. Scale reliability …

Development And Validation Of The Emergency Department Transitions Measure, Sara Beachy, Danielle M. Mccarthy, Julianna Lenoir, Alexzandra Gentsch, Richard W. Hass, Marissa Witmer, Paula Ostroff, Melissa Tupas, Lindsey Shughart, Hailey Shughart, Kristin L. Rising

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: Transitions of care are high-risk periods for patient safety in the emergency department (ED), particularly for patients who are still in the diagnostic process and are discharged with diagnostic uncertainty. Care transitions must be improved for these patients, as one third of discharged ED patients have diagnostic uncertainty. Yet there are no validated measures that assess the quality of care transitions from the ED, limiting the ability to assess the impact of interventions. Thus, we developed and validated the ED Transitions (EDT) measure.

METHODS: This mixed methods study was conducted across a large healthcare system in three phases: item …

Fungal Meningitis In Us Patients Who Received Epidural Anesthesia In Matamoros, Mexico, Dallas J Smith, Elizabeth Misas, Jeremy A W Gold, Nicole Evert, Thi Dang, Emilie Prot, Simone Godwin, Julieanna Rivas, Jessica Pearson, Lori Koenecke, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Irma López-Martínez, Caitlyn Lutfy, Samantha Williams, Axel A Vazquez Deida, Katrina M Byrd, Julian A Villalba, Sarah Reagan-Steiner, Lindsay Parnell, Lalitha Gade, Romney M Humphries, Nathan P Wiederhold, Charles Y Chiu, Joshua A Lieberman, Anastasia P Litvintseva, Tom Chiller, Luis Ostrosky-Zeichner, Fungal Meningitis Response Team

Faculty, Staff and Student Publications

Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in US patients who received epidural anesthesia in Matamoros, Mexico.

Methods: Early epidemiological information suggested US patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in 2 Matamoros clinics. US patients known to have received surgery at these clinics during 1 January-13 May 2023 (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, …

Multimodal Imaging Reveals A Lysosomal Drug Reservoir That Drives Heterogeneous Distribution Of Parp Inhibitors, Carmen R Moncayo, Lauren Pendergast, Priyanka Verma, Et Al.

2020-Current year OA Pubs

For all drugs, effective target engagement requires sufficient intracellular concentrations of drug to be reached, but whether tumour heterogeneity impacts drug distribution and efficacy is poorly studied. Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed treatment opportunities for women with high-grade serous ovarian carcinoma, but resistance remains a clinical hurdle in this highly heterogeneous tumour type. Here, we present a patient-derived explant multi-modal imaging pipeline, which demonstrates that cell-intrinsic PARP inhibitor accumulation is highly variable, both between patients and within tumours. Spatial transcriptomics reveals enrichment of apoptotic and lysosomal signatures in high-drug regions. Rucaparib, an intrinsically fluorescent PARP inhibitor, accumulates heterogeneously …

Dexmedetomidine On Supraventricular Tachycardia In Critical Illness: A Time-Dependent Propensity Score Matching Study, Qiaonan Zhong, Marin H Kollef, Patrick G Lyons, Andrew P Michelson

2020-Current year OA Pubs

BACKGROUND: Supraventricular tachycardia affects many critically ill patients. Dexmedetomidine, a commonly used sedative, has sympatholytic and vagotonic effects that may alter atrioventricular nodal conduction and contribute to SVT. We aim to determine the association between dexmedetomidine exposure and clinically significant supraventricular tachycardia in a heterogeneous cohort of mechanically ventilated, critically ill adults. METHODS: This retrospective cohort study included critically ill patients from 11 hospitals admitted between July 2018 and October 2022, who were intubated within 48 h of admission. The primary exposure was intravenous dexmedetomidine. The primary outcome was occurrence of clinically significant supraventricular tachycardia, defined as heart rate > 100 …

Integrative Multiomic Classification Reveals Distinct Origins And Evolutionary Trajectories Of Thymic Epithelial Tumors., Seongyeol Park, Kijong Yi, Jieun Lee, Myung Jin Yang, Joo-Hye Song, Joonoh Lim, Taewoo Kim, Seokhwi Kim, Su Yeon Kim, Hyung-Don Kim, Yoon Ho Kim, Sae Bom Lee, Yoo Jin Jung, Hansol Park, Jake June-Koo Lee, Yohan An, Jeonghwan Youk, Kwon Joong Na, Samina Park, Hyun Joo Lee, In Kyu Park, Chang Hyun Kang, Eui-Cheol Shin, Tae Min Kim, Won Do Heo, Charles Lee, Gou Young Koh, Sung-Yup Cho, Young Seok Ju, Young Tae Kim

Faculty Research 2026

Thymic epithelial tumors (TET), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells (TEC). Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. In this study, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases, combined with 117 cases from publicly available datasets. Single-cell transcriptomic data from murine thymic tissues across developmental stages were incorporated to further …

Short-Term Sleep Restriction In Humans Alters Diurnal Circulating Metabolite Profiles, Including Those Of Microbial Origin., Vanessa A Leone, Katya Frazier, Manpreet Kaur, Evan A Chrisler, Ashley M Sidebottom, Ethan Tai, Vilinh Tran, Shuzhao Li, Eugene B Chang, Dean P Jones, Eve Van Cauter, Erin C Hanlon

Faculty Research 2026

BACKGROUND. Gut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.

METHODS. In a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were …

Short-Term Sleep Restriction In Humans Alters Diurnal Circulating Metabolite Profiles, Including Those Of Microbial Origin., Vanessa A Leone, Katya Frazier, Manpreet Kaur, Evan A Chrisler, Ashley M Sidebottom, Ethan Tai, Vilinh Tran, Shuzhao Li, Eugene B Chang, Dean P Jones, Eve Van Cauter, Erin C Hanlon

Faculty Research 2026

BACKGROUNDGut microbes and their metabolites contribute to the host circulating metabolome and exhibit diurnal variation influenced by sleep-wake cycles and meal timing. Sleep deprivation alters the rhythmic circulating metabolome, but its impact on microbial metabolites remains unclear. We tested whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep.METHODSIn a randomized crossover design, 9 healthy adults completed 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were held constant. Serum …

Integrative Multiomic Classification Reveals Distinct Origins And Evolutionary Trajectories Of Thymic Epithelial Tumors., Seongyeol Park, Kijong Yi, Jieun Lee, Myung Jin Yang, Joo-Hye Song, Joonoh Lim, Taewoo Kim, Seokhwi Kim, Su Yeon Kim, Hyung-Don Kim, Yoon Ho Kim, Sae Bom Lee, Yoo Jin Jung, Hansol Park, Jake June-Koo Lee, Yohan An, Jeonghwan Youk, Kwon Joong Na, Samina Park, Hyun Joo Lee, In Kyu Park, Chang Hyun Kang, Eui-Cheol Shin, Tae Min Kim, Won Do Heo, Charles Lee, Gou Young Koh, Sung-Yup Cho, Young Seok Ju, Young Tae Kim

Faculty Research 2026

Thymic epithelial tumors (TET), comprising various histologic types of thymomas and thymic carcinomas, originate from thymic epithelial cells (TEC). Each histologic type is typically associated with a distinct immune cell composition and clinical manifestation. A better understanding of the cellular origins and molecular pathways underlying this heterogeneity is needed to improve patient stratification and treatment. In this study, we conducted an integrated genomic and transcriptomic analysis of 124 thymomas and 13 thymic carcinomas, including 20 newly sequenced cases, combined with 117 cases from publicly available datasets. Single-cell transcriptomic data from murine thymic tissues across developmental stages were incorporated to further …

Ifnγ-Induced Antigen Loss In Chimeric Antigen Receptor-T Cell Therapy, Miao Cao, Jasmine Alvarez, Ramkrishna Mitra, Michael Xu, Trevor R. Baybutt, Zhengyang Sun, Oluwatobiloba Taylor, Allison Doermann, Ross E Staudt, Scott A. Waldman, Adam E. Snook

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

INTRODUCTION: FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for "solid" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFNγ has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.

METHODS: Using

RESULTS: We identified …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder

Faculty, Staff and Student Publications

Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.

Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).

Results: SVI percentile was 0.4 (interquartile ratio …

Vascular Contribution To Cognitive Impairment And Dementia (Vcid): Proceedings Of 2025 Workshop Of The Jackson Laboratory., Mehwish Anwer, Tetiana Poliakova, Ricardo D'Oliveira Albanus, Mohammad Iqbal H Bhuiyan, Adam M Brickman, Soumilee Chaudhuri, Leah Cuddy, Maxwell Eisenbaum, Kate Foley, Douglas B Gould, Catherine Hall, Costantino Iadecola, Olivia J Marola, Christopher M Norris, Alaina M Reagan, Julie Schneider, Donna Wilcock, Isabella Xu, Andrew Yang, Gareth R Howell, Cheryl L Wellington

Faculty Research 2026

The first Vascular Contributions to Cognitive Impairment and Dementia (VCID) Workshop, held on May12-16, 2025 at The Jackson Laboratory, provided scientific content and career development training in the latest developments in VCID and Alzheimer's Disease (AD) and related dementia (ADRD). The Workshop aimed to foster interdisciplinary collaborations and empower the next generation of diverse scientists to advance ADRD research from mechanism to intervention. The meeting placed a strong emphasis on neurovascular pathology, its central role in ADRD pathogenesis, its modulation by both central and peripheral factors, and the critical need to dissect the mechanistic basis of VCID through experimental models. …