Digital Commons Network^™

Navigating A Delicate Balance: Antibiotic Allergy In The Setting Of Renal Infection And Diabetic Ketoacidosis, Aun Bangash, Muhammad Bangash, Ruben M. Martinez Meza

School of Medicine Publications

Acute pyelonephritis is a bacterial infection of the renal parenchyma that requires prompt recognition and antibiotic therapy to prevent complications such as sepsis and chronic renal inflammation. We present a case of a 26-year-old woman with poorly controlled type 1 diabetes mellitus and a documented beta-lactam allergy who presented with atypical symptoms, including flank pain without urinary complaints. Laboratory evaluation demonstrated leukocytosis with a negative urinalysis. CT of the abdomen revealed left lobar nephronia with early contralateral involvement of the right kidney. Given her allergy history, she was treated with levofloxacin. During her hospital stay, she developed nausea, vomiting, and …

Examining The Benefits Of A Standardized Protocol For Hyperglycemia Screening In Adult Oncology Patients: A Pilot Study, Alexa Dashko

Pacific Journal of Health

Many individuals receiving cancer directed therapy are at risk of developing hyperglycemia and new, or worsening of, diabetes due to location of their cancer, treatment regimen, and/or prolonged use of steroids. Research shows that uncontrolled hyperglycemia can have detrimental effects on individuals’ response to cancer therapy, treatment associated toxicities, quality of life and overall mortality. Despite extensive research identifying the need for routine monitoring and management of hyperglycemia in oncology patients, medical societies have yet to establish formal screening guidelines for practitioners. The aim of this pilot study was to examine the outcomes of establishing a protocol for screening and …

Dermal: A Multi-Input Deep Learning Model For Improving Access To Dermatological Screening, Aubreye Freeman

ATU Scholars Symposium

According to the World Health Organization's press release on December 12, 2024, global healthcare spending is dropping significantly, leaving a large percentage of the world without proper healthcare. In an attempt to alleviate this problem, with respect to the field of dermatology, we created a deep learning model, Dermatology Enhanced by Recognition and Machine Aided Learning (DERMAL), to assist in diagnosing skin conditions. DERMAL was trained on a portion of the Google and Stanford Medicine's SCIN dataset, which has more than 10,000 images of various skin conditions. The 9 most common skin conditions of the dataset were selected as the …

Abstract Book (Pdf), Department Of Psychiatry

Dept. of Psychiatry Research Symposium

Abstract book for the 4th Annual Department of Psychiatry Research Symposium held April 9, 2026.

Reirradiation Treatment Effects In The Clinic (Retec) Proposal - Proof Of Concept Based On Spinal Cord Dose Tolerance For Reirradiation With Stereotactic Body Radiotherapy, Jimm Grimm, Anand Mahadevan, Olusola Obayomi-Davies, Scott G. Soltys, Arjun Sahgal, Kristin J. Redmond, Michael T. Milano, Wolfgang A. Tomé, Kenneth Brooks, Scott Dodd, John Austin Vargo, Gopal Subedi, Jinyu Xue, Bisher Ebid, Felix Ehret, Byung-Han Andrew Rhieu, Christoph Fürweger, Rachel Grimm, Alexander Muacevic, Vitali Moiseenko, Shalom Kalnicki, Mark Mclaughlin, Lawrence R. Kleinberg, John R. Adler, Iris C. Gibbs

College of Health Professions Faculty Papers

BACKGROUND: Since the inception of spinal radiosurgery decades ago, the factors influencing spinal cord recovery have remained unclear. Elucidating these factors would aid in reirradiation planning and delivery. We describe modeling reirradiation normal tissue complication probabilities (NTCP) from compiled published data, akin to the collaborative Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and High Dose per Fraction, Hypofractionated Treatment Effects in the Clinic (HyTEC) projects.

PURPOSE: Simple dose-time recovery factors for the spinal cord serve as a basis to propose the Reirradiation Treatment Effects in the Clinic (ReTEC) project. ReTEC aims to define human organ recovery factors …

The Use Of Radiofrequency In The Treatment Of Erectile Dysfunction, Sarah Ponce, Nikola Rakic, Beatriz Hernandez, Mohit Khera

Faculty, Staff and Students Publications

No abstract provided.

Multi-Organ Physiologic Deficits During Exercise Identify Clinical And Molecular Predisposition To Heart Failure With Preserved Ejection Fraction, Isabela Landsteiner, Lindsey K Stolze, Tess E Peterson, Andrew Perry, Phillip Lin, Quanhu Sheng, Shilin Zhao, Kaushik Amancherla, Michael Y Mi, Takenori Ikoma, Laura P Cohen, Ilya Giverts, Joseph Campain, Joao A C Lima, Wendy S Post, Kent D Taylor, Robert Gerszten, Stephen S Rich, Russell Tracy, Peter Durda, Alexis C Wood, Rajeev Malhotra, Jerome I Rotter, Clary Clish, Matthew Nayor, Eric R Gamazon, Ravi V Shah, Gregory D Lewis

Faculty, Staff and Students Publications

Background: Exercise unmasks limitations in multi-organ system reserve capacity characteristic of heart failure with preserved ejection fraction (HFpEF). However, the metabolic and genetic underpinnings of exercise deficits, and their cumulative contribution to HFpEF severity and prognosis, remain incompletely understood.

Methods: We used invasive cardiopulmonary exercise testing (iCPET), metabolite profiling, and genomics to simultaneously characterize seven exercise physiologic deficits in HFpEF patients: reduced exercise stroke volume and heart rate, steep pulmonary capillary wedge pressure/cardiac output (PCWP/CO) slope, elevated pulmonary vascular resistance, pulmonary mechanical limitation to exercise, impaired peripheral oxygen extraction, and obesity-related exaggerated metabolic cost of initiating exercise. We first mapped …

The Impact Of A Mindfulness Meditation Program On Phq-9 Scores In Eskd Clients At The Dialysis Center, Christi Collins Weaver

Student Scholarly Projects

Practice Problem: Patients undergoing hemodialysis for end-stage kidney disease (ESKD) experience high rates of untreated depressive symptoms, which negatively impact quality of life, treatment adherence, and therefore increased hospitalization and higher mortality rates.

PICOT: In adult patients receiving in-center hemodialysis (P), how does the implementation of a structured mindfulness meditation program (I), compared to usual care (C), affect depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) (O) over an eight-week period (T)?

Evidence: Current literature demonstrates that depression is highly prevalent among individuals with ESKD and is associated with increased morbidity and decreased treatment adherence. Evidence supports mindfulness …

Relative Impact Of Multidomain Lifestyle Interventions On Deficit Accumulation Frailty Over 24 Months In The U.S. Pointer Trial, Mark A Espeland, Kayloni Olson, Christy C Tangney, Darren R Gitelman, Maryjo Cleveland, Amber A Thro, Yitbarek N Demesie, Heather M Snyder, Rachel A Whitmer, Pankaja Desai, Rifat Alam, Lucia Crivelli, Thomas M Holland, Olivia Preissle, Rema Raman, Michele K York, Laura D Baker

Faculty, Staff and Students Publications

Background: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk, but the degree to which multidomain lifestyle changes impact frailty is not clear.

Methods: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability …

A Prolonged Nightly Fasting Plus Telehealth Coaching Intervention (Pnf+) For Men On Androgen Deprivation Therapy For Pca: A Pilot Feasibility Randomized Controlled Trial, Kuang-Yi Wen, Julianne Freedman, Kevin K. Zarrabi, Rachel Slamon, Rita Smith, Jessica Liang, Patrick Mille, William J. Tester, William Kevin Kelly

Department of Medical Oncology Faculty Papers

Background/Objectives: This study aimed to assess the feasibility and acceptability of a 3-month health coaching intervention to promote PNF and healthy diet for men on ADT for PCa.

Methods: The study was carried out via a two-armed randomized controlled trial including 40 patients with PCa at a medical center in Philadelphia. During the 3-month period, the intervention group (PNF+) received health coaching utilizing an interactive text message system, and the control group received healthy eating text messages for the same duration. The outcome variables were feasibility and acceptability.

Results: The PNF+ group (n = 27) had high …

Improving Anesthesia Provider Confidence In The Identification, Management, And Treatment Of Postoperative Delirium, Brittany M. Whistle, Charles Dustin Phelps

Scholars Week

Purpose: Postoperative Delirium (POD) is a potentially devastating complication of anesthesia that is poorly understood by clinical staff leading to poor outcomes for surgical patients. This study is meant to determine if a focused knowledge presentation accompanied by visual aids could increase anesthesia providers confidence in identifying, diagnosing, and treating Postoperative Delirium.

Methodology: Utilizing a statistical model to analyze respondents results on a standardized test administered before and after an informational presentation with visual aids on the topic of Postoperative Delirium.

Results: Results indicated a statistically significant difference between pretest and posttest scores, with a p-value of .002, t(11) = …

Plastics, Microplastics, And The Gut Microbiome: Restoring Scientific Communication To Fight For Public Health, Benjamin Sanders '26

Honor Scholar Theses

Over the course of eight years from 2016 to 2024, a study by Nature Medicine found that the concentration of plastics in the brain increased by 50%. Even samples from patients with a documented dementia diagnosis showed a greater accumulation of microplastics (Nihart, 2025). In one of the most protected regions of our body, microplastics have made themselves known. In one of the most exposed regions of the human body, the story is no different. With the emergence of gut microbiome science and understanding, researchers are just beginning to discover the unique interplay between the microbiota of our gastrointestinal tract …

Cardiovascular Adaptation To Whole-Body Vibration Exercise In Obese Young Adults: A Systematic Review, Meta-Analysis, And Exploratory Analysis Of Sex Differences, Rafiu Okuneye, Abdulkareem Taiwo, Fatai Akinola Apalara, Okechukwu Kingsley Oforka, Isaiah Whenayon Ajoseh, Ogar Emmanuel Ekawu

Indonesian Journal of Research in Physical Education, Sport, and Health

Background: Obesity is strongly associated with hypertension and autonomic dysfunction. Whole-body vibration exercise (WBVE) has been proposed as a low-impact intervention for improving cardiovascular function in obese adults, but sex-specific responses remain unclear. Objective: This study aimed to evaluate the effects of whole-body vibration exercise on blood pressure, autonomic function, and cardiac output in adults with obesity, and to explore potential sex differences in cardiovascular adaptations. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies examining the effects of WBV on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate variability (HRV), and …

Dietary Patterns And Nutritional Status In Soccer Athletes: A Cross-Sectional Study From An Ergonomic Perspective, Rina Mayangsari, Ravi Masitah

Indonesian Journal of Research in Physical Education, Sport, and Health

Background: Normal nutritional status has been established as one of the principal determinants in an athlete's performance. Dietary quality plays a critical role in optimizing athletes' physical fitness and performance outcomes. Objective: To examine the associations between dietary patterns on the MacPersona System and nutritional status of soccer players (energy, protein, et cetera, fat, and carbohydrates). Methods: A cross-sectional quantitative study was conducted involving 21 soccer players (total sampling). Dietary patterns were assessed using a validated Semi-Quantitative Food Frequency Questionnaire (SQ-FFQ). Nutritional status was measured using Body Mass Index(BMI) based on anthropometric data. The chi-square test was used for statistical …

Cardiomyopathy In Children: What Pediatricians Need To Know, Michael Smith, Brian Birnbaum

Pediatrics in Practice: A CME Podcast

Cardiomyopathy in children can present with subtle signs but serious consequences if missed. In this episode, Brian Birnbaum, MD, Interim Co-Director of the Ward Family Heart Center at Children’s Mercy, shares practical insights for pediatricians on recognizing early red flags, knowing when to refer, and understanding how diagnosis and management of pediatric cardiomyopathy are evolving.

Click here to stream the podcast episode.

Emergency Care Outside Of The Four Walls Of The Emergency Department, Judd E. Hollander

Department of Emergency Medicine Faculty Papers

No abstract available

La Dolce Vita Or The American Way: A Comparative Study Into The Italian And American Healthcare Systems Through An Analysis Of Total Knee Replacements, James (Jim) Mcmurray '26

Honor Scholar Theses

This thesis presents a comparative study of the Italian and the American healthcare systems, using Total Knee Replacements (TKRs) as a standardized metric to evaluate the health policy, financing, and patient outcomes. Despite the United States spending over $10,000 more per capita on healthcare than Italy, American life expectancy is 5 years shorter than Italian life expectancy. Through a mixed-methods analysis of data from the American Joint Replacement Registry (AJRR), the Programma Nazionale Esiti (PNE), the Registri Italiani di ArtoProtesi (RIAP), and the HCUPnet (AHRQ) database, this research identifies multiple disparities throughout the system. Key findings in this thesis include …

Non-Diabetic Kidney Disease In A Patient With Type 2 Diabetes Mellitus: A Diagnostic Challenge, Nikhil R, Mahabaleshwar Mamadapur , Assistant Professor, Harshwardhan S Patil

Digital Journal of Clinical Medicine

Background: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease. However, non-diabetic kidney disease (NDKD) can coexist or mimic DKD, leading to misdiagnosis. Case Presentation: A 46-year-old female with type 2 diabetes presented with vomiting and abdominal pain. Physical examination revealed non-blanching erythematous papules on both lower limbs. Investigations showed uncontrolled diabetes, metabolic acidosis, and active urinary sediment. Absence of diabetic retinopathy prompted renal biopsy, which revealed immune-complex–mediated glomerulonephritis with small-vessel vasculitis. Diagnosis: Immune-complex–mediated glomerulonephritis with small-vessel vasculitis, not consistent with diabetic nephropathy. Management: Supportive care and immunosuppressive therapy were initiated with improvement in renal function. …

Balneotherapy For Sleep Improvement And Reducing Depression In Knee Osteoarthritis Patients, Anca Paula Ciurba, Alexandru Bogdan Ilieș, Ionel Haidu, Doriana Ioana Ciobanu, Theodora Ursu, Florin Mihai Marcu, Dorina Ianc

Baltic Journal of Health and Physical Activity

Background: Knee osteoarthritis (OA) is the most common chronic condition and a leading cause of global disability, often associated with pain, depression, and sleep disturbances. The purpose of this study was to investigate the effectiveness of warm mineral water combined with physical therapy on sleep quality, depression and pain intensity in patients with knee osteoarthritis. Materials and Methods: The study involved 101 subjects (68.78±6.92 years) who were assigned to  a control group (CG) or an experimental group (EG). All subjects benefited from physical therapy and electrotherapy for 10 days. The experimental group additionally benefited from therapy with hot mineral water. …

Six-Week Time-Restricted Eating Lowers Premature Mortality Risk In Overweight Early Elderly Adults: Evidence From A Body Shape Index, Przemysław Domaszewski, Mariusz Konieczny

Baltic Journal of Health and Physical Activity

Background: A Body Shape Index (ABSI) is an anthropometric indicator combining waist circumference, weight, and height, providing a BMI-independent measure of central obesity and a recognized predictor of mortality. Despite its relevance, research on ABSI in early elderly populations remains limited. This study assessed the impact of a six-week time-restricted eating (TRE) intervention on ABSI z-scores in overweight adults aged 65–74, with attention to gender differences. Materials and Methods: A total of 116 participants were randomized into a TRE group (16:8 fasting window from 8:00 PM to 12:00 PM) or a control group maintaining habitual eating. ABSI z-scores were evaluated …

Changes In 25(Oh)D Concentration, Bone Resorption Markers And Physical Performance Due To Sun Exposure, Diet And Training Load Among Professional Women Handball Players During The Half-Year Training Season, Sorin Dacian Buhas, Zbigniew Jastrzębski, Paul Florian Dragos, Marius Alin Marinau, Maria Skalska, Mirela Stef, Joanna Jastrzębska, Mihai Sandra, Dana Ioana Cristea

Baltic Journal of Health and Physical Activity

Background: The aim of the study was to demonstrate changes in 25(OH)D concentration, bone resorption indicators and physical fitness in female handball players as a result of their exposure to the sun, diet and exercise load during the six-month training period from mid-March to mid-September, i.e. the time when the sun exposure is the highest during the calendar year. Twenty-two women handball players participated in the study. Due to the random occurrences and exclusion criteria, 20 players completed the project. Biochemical analysis of blood, aerobic capacity, running speed and power tests (Wingate test, squat jump, counter movement jump, etc.) was …

Drd2 Rs6276 Polymorphism And Trait Impulsivity In Individuals With Mixed Behavioral And Substance Addictions, Gabriela Zdunek, Remigiusz Recław, Aleksandra Suchanecka, Krzysztof Chmielowiec, Dariusz Larysz, Patryk Ilków, Kinga Łosińska, Jolanta Chmielowiec, Łukasz Jaworski, Anna Grzywacz

Baltic Journal of Health and Physical Activity

Background/Objectives: Impulsivity is a key transdiagnostic trait linked to dysregulated reward processing in both behavioral and substance-related addictions, as recognized in DSM-5. Dopaminergic genes, including DRD2, may modulate individual differences in impulsivity, particularly under conditions of increased addiction vulnerability. This study examined whether the DRD2 Exon 8 rs6276 polymorphism predicts impulsivity levels in men with mixed addictive behaviors compared with healthy controls. Methods: A total of 328 males (128 with mixed behavioral and substance addictions and 200 controls) were assessed. Diagnoses were confirmed using the MINI interview, and impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11). Genotyping of …

Inside The Therapy Room: What Really Happens In A Session With Your Kid, Maggie Mckay, Haley J. Killian

Parent-ish Podcast

Ever wonder what your kid actually does in therapy? In this episode, pediatric psychologist Haley Killian, PhD, gives us a simple, behind‑the‑scenes look at what happens in a session—play, feelings, progress and all. It’s real talk, zero judgment, and plenty of reassurance for any parent curious about whether therapy could help their kid.

Click here to stream the podcast episode.

Breaking Barriers: Advancement Toward Practical Nursing Licensure For Certified Medication Assistants In Long-Term Care--A Descriptive Study, Aleshia L. Maxwell

ATU Theses and Dissertations 2021 - Present

The persistent nursing shortage across the United States, particularly in Long-Term Care (LTC) settings, has complicated the healthcare system’s ability to meet the needs of an aging population. While existing research often examines progression from Licensed Practical Nurse (LPN) to Registered Nurse (RN), limited research explores factors influencing progression from entry-level LTC healthcare workers to Practical Nursing (PN) licensure. This quantitative descriptive study examined the barriers and supporting factors influencing advancement toward PN licensure for Medication Assistants-Certified (MA-Cs) in Arkansas LTC facilities. A convenience sample of N=100 participated in the study. Results indicated that financial and structural barriers often …

Nanog Proximity Proteomics Maps Neighborhood Hubs Linked To Mesenchymal Stem Cell Stemness And Chromatin Control, Kyoung-Jae Choi, Michail Tyryshkin, Harathi Jonnagaddala, Allan Chris M Ferreon, Marian Kalocsay, Josephine C Ferreon

Faculty, Staff and Students Publications

NANOG overexpression has been reported to reverse aging-associated decline in mesenchymal stem/stromal cell (MSC) function, but the molecular machinery engaged by NANOG in MSCs remains incompletely defined. Here, we applied APEX proximity labeling coupled with quantitative mass spectrometry to define the NANOG proximity interactome (proxeome) in human MSCs. Of 1040 quantified proteins, 828 were significantly enriched in the APEX-NANOG (H2O2 labeling) samples, consistent with a broad NANOG-centered neighborhood rather than a single stoichiometric complex. Enriched proteins encompass RNA-processing pathways (including splicing/RNP factors and selected m6A-related proteins), transcriptional coactivation and elongation control (Mediator and 7SK/P-TEFb regulators), chromatin repression/poising modules (Polycomb and …

Unpacking Developmental Programming: A Conceptual And Historical Analysis In The Context Of Dohad, Andrea Gretchev, Heide S. Temples, Gillian England-Mason, Deborah Dewey, Sara M. Sarasua, Christopher Farrell, Vivian Haley-Zitlin

Publications

The Developmental Origins of Health and Disease (DOHaD) paradigm posits that early environmental factors may influence a child’s development and long-term health outcomes. Developmental programming (DP) is central to this paradigm, whereby specific early life exposures during critical periods of development are associated with changes to physiological and metabolic pathways, potentially predisposing individuals to disease. However, no standard definition of DP exists, and various terms have been used to describe similar processes. This analysis aimed to develop a conceptual definition for DP to inform interdisciplinary research, education, and practice. Walker and Avant’s eight-step method was employed to analyze the literature, …

Predicting Ventilation From Single Breathing Phase Non-Contrast Ct Using Swin Transformers, Yi-Kuan Liu, Hsu-Ting Kuo, Alaa Melek, Richard Castillo, Yevgeniy Vinogradskiy, Lili Zhao, Girish Nair, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Pulmonary ventilation imaging enables functional avoidance radiotherapy treatment plans by quantifying regional lung function. However, current clinical standards, such as 99𝑚Tc-based single-photon emission computed tomography (SPECT), rely on radioactive tracers, which can introduce imaging deposition artifacts. CT ventilation imaging (CTVI) methods based on both physical models and deep learning approaches currently require multiple CT images as input, such as the inhale/exhale phases of a 4DCT. While the theoretical foundation of physics-based CTVI is built on multi-phase information, the feasibility of single-phase deep learning CTV models has not been determined.

PURPOSE: While deep learning methods have predicted SPECT ventilation from …

Computed Tomography For Four-Dimensional Dose Calculation: Effect Of Detector Array Length, Inhwan Yeo, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: Four-dimensional computed tomography (4DCT) is susceptible to a geometrical error when respiration changes upon patient shift. 4DCT using 16-cm detector arrays, not needing the shift, has been shown to improve geometrical accuracy, compared with a conventional 4DCT (4-cm array), albeit with some Hounsfield unit discrepancies. The 4DCTs were validated for 4D planning.

MATERIALS AND METHODS: A lung-mimicking phantom containing a spherical target with ten respiratory traces and three tumor-shaped targets with their traces was respectively imaged when, to each of the ten-positions/phases, the lung was moved (1) step-wisely by helical scan at each movement (ground truth; 4DCT_GT), …

Transcultural Headache Medicine: A Framework For Integrating Cultural Contexts Into Headache Science And Care - A Call To Action From The International Headache Society., Mario F. P. Peres, Giancarlo Lucchetti, Homero Vallada, Ivy L. Riso, Georgia K. Westenhofen, Marcelo Moraes Valença, Juliana Ramos De Andrade, K. C. Brennan, Morris Levin, Tsubasa Takizawa, Zhao Dong, Yonggang Wang, Wanakorn Rattanawong, Henry Riyanto Sofyan, Massimo Leone, Freda Dodd-Glover, Hsiangkuo Yuan, Abdulrazaq Albilali, Taoufik Alsaadi, Leonardo Caixeta, Anna P. Andreou, Peter J. Goadsby, Antoinette Maassenvandenbrink, Sait Ashina, Rami Burstein, Patricia Pozo-Rosich, Fayyaz Ahmed, Shuu-Jiun Wang

Department of Jefferson Headache Center Papers and Presentations

Headache disorders are among the most disabling neurological conditions, affecting over 1.5 billion people globally. Despite advances in pharmacological therapies, major inequities persist due to underdiagnosis, undertreatment and limited access to effective care, particularly in low- and middle-income countries. Social determinants of health, including cultural meanings, language and health beliefs, are increasingly recognized as key drivers of disparities in burden, diagnosis and treatment outcomes. Traditional medicine, used by more than 80% of the global population, remains first-line care in many regions and continues to influence therapeutic choices in high-income settings. Major systems such as Ayurveda, Traditional Chinese Medicine, Unani and …

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng, Nicolas L Young, Marco Sardiello

Center on Aging Staff Publications

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues …