Medicine and Health Sciences Commons^™

Effects Of Concurrent Neuropathologies With Alzheimer Disease Neuropathologic Change On Cognitive Decline: Minimal Impact Of Vascular Brain Injury Compared With Other Combinations, Sarah M Yasuda, Charles Mock, Kathryn Gauthreaux, Kwun C G Chan, C Dirk Keene, Jessica E Culhane, Yen-Chi Chen, Walter Kukull

2020-Current year OA Pubs

We examined cognitive changes associated with several neuropathologic entities, alone and in combination. We studied 808 participants from the National Alzheimer's Coordinating Center to assess associations between neuropathologic diagnoses (from autopsy) and neuropsychologic test scores (trajectories over time for 5 domains: overall cognition, episodic memory, attention, language, executive function). Neuropathologies included: Alzheimer disease neuropathologic change (ADNC), Lewy body disease (LBD), vascular brain injury (VBI), and limbic-predominant age-related TDP43 encephalopathy neuropathologic change (LATE-NC). Using linear mixed-effects models, we examined trajectories of cognitive decline for ADNC alone compared to ADNC plus LBD, VBI, or LATE-NC. We also examined differences between observed trajectories …

Navigating Undone Science: The Search For Adequate Endometriosis Care, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Endometriosis is an estrogen-dependent disease in which tissue similar to the lining of the uterus grows elsewhere in the body leading to a variety of symptoms including heavy and prolonged menstruation, chronic pain, cysts, infertility, and gastrointestinal issues. Despite being one of the most common gynecologic conditions, much remains unknown about potential risk factors for endometriosis, its etiology, and treatment options. First and second-line biomedical treatment options, complementary and alternative medicine, and lifestyle changes are all treatment options that people living with endometriosis (PLE) leverage to manage their symptoms. This article draws on in-depth interviews with 52 people living with …

Oral History With John Barry, Dan Royles

History Faculty Scholarship

Oral history interview with John Barry, who has served as Executive Director of the Southern Tier AIDS Program (STAP) since 2008. He was born in Endicott, New York in 1966, grew up in Vestal, and attended high school at Seton Catholic Central in Binghamton before serving in Germany with the United States Army during the early 1980s. When he returned to Broome County in 1987, some of his friends had been affected by HIV/AIDS and, while earning a degree at SUNY Binghamton, Barry became involved in mutual aid efforts to help people affected by the disease. He went to work …

A Prospective Study Of Hyperspectral Imaging For Lower Extremity Tissue Assessment In Normative And At-Risk Populations, Jessica Sima, Mariana Rodriguez, Stephanie Campbell, Amanda Killeen

School of Podiatric Medicine - Student Research

Introduction:  Diabetic foot ulceration and peripheral vascular disease remain major causes of morbidity and limb loss, yet early identification of tissue compromise can be challenging, particularly across diverse skin tones. Hyperspectral imaging (HSI) is a non-invasive technology that quantifies tissue oxygenation by measuring the absorption and reflection of near-infrared light.

The objective of this study is to evaluate the relationship between oxygenation, skin tone, skin temperature, and ambient skin temperature in adults with and without risks of foot ulcers.

Method: This ongoing prospective observational study recruits English- and Spanish-speaking adults aged 18 and over from campus, clinics, and community outreach …

Comparative Effectiveness Of Antiseptic And Antibiotic Irrigation Versus Normal Saline In Infected Total Ankle Arthroplasty: A Systematic Review, Madelaine Adkins, Yahan Wei, Amanda Killeen

School of Podiatric Medicine - Student Research

Introduction: Periprosthetic joint infection (PJI) is a rare but devastating complication following total ankle arthroplasty (TAA). Acute infections are commonly managed with debridement, antibiotics, and implant retention (DAIR), in which irrigation plays a critical role in reducing bacterial burden. Although irrigation protocols have been investigated in total hip and total knee arthroplasty, evidence specific to infected TAA remains unclear. This systematic review evaluated the available literature regarding irrigation practices in the surgical management of infected TAA.

Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed and Scopus were search for English-language studies published between December 2005 and …

Select Plasma Oxylipins As Potential Biomarkers Of Effective Indomethacin Treatment Response In Preterm Infants With Patent Ductus Arteriosus., Khanh C K Nguyen, Cindy H T Yeung, Allison Scott, Thomas J. Velenosi, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Patent ductus arteriosus (PDA) is one of the most common heart conditions in preterm infants, and indomethacin treatment is used for PDA closure. However, its efficacy varies among patients. This pilot study aimed to identify novel metabolic biomarkers to predict effective indomethacin response in infants with PDA.

METHODS: Preterm infants with PDA <  34 weeks gestational age were recruited and treated with indomethacin. Plasma and urine samples were collected before and 2-7 days after initial treatment. Longitudinal targeted oxylipin and untargeted metabolomics analysis were performed on plasma and urine samples.

RESULTS: Among 17 infants, 12 were responders and 5 non-responders to indomethacin treatment. Before the treatment, four plasma oxylipins: 12,13-DiHOME, 9,10-DiHOME, 15,16-DiHODE, and 9,10-DiHODE were significantly higher in responders compared to non-responders (P <  0.05). Following treatment, these oxylipins decreased in responders but remained stable in non-responders. Urinary 12,13-DiHOME showed an opposite trend, with lower baseline concentrations in the responders.

CONCLUSIONS: Pre-treatment plasma levels of four oxylipins were associated with effective PDA response to …

The Role Of Mitochondria In The Pathogenesis Of Parkinson’S Disease, Oyinkansola Mudasiru, Vivian Etugbo, Bhuvana Lakkasetter, Claudia Biguetti, Reginald Adiele

School of Podiatric Medicine - Student Research

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of the dopaminergic neurons of the substantia nigra that leads to motor and non-motor dysfunctions. Emerging evidence highlights mitochondrial dysfunction as a key factor in PD pathogenesis. This project aims to investigate the pathophysiology of PD, highlighting the involvement of oxidative stress, and examining current and emerging therapeutic approaches aimed at restoring mitochondrial function.

Methodology: A systematic literature review was conducted using PubMed and Google Scholar within the 2004-2024 date range. Keywords included “Parkinson’s disease”, “mitochondrial dysfunction", “oxidative stress”, and neurodegeneration”. Data was extracted regarding …

Public Responses About Air Quality In The World’S Ten Most Populous Countries, Noah Lim, Alessandro Del Ponte, Lina Ang, Wei Jie Seow

Political Science Faculty Articles and Research

Understanding how people view and react to outdoor air quality is crucial to effectively managing and responding to air pollution, which is a major threat to global public health. Using a quota sample of 10,618 respondents from 1,372 localities across the world’s ten most populous countries (Bangladesh, Brazil, China, Indonesia, India, Mexico, Nigeria, Pakistan, Russia, and the United States), we assessed the association between exposure to fine particulate matter with diameter ≤ 2.5 micrometers (PM2.5) and people’s knowledge, attitudes, perceptions, practices, and concern about air quality. Overall, we find an inverse association between air pollution exposure and knowledge about air …

“It’S Not Just Cost”: Barriers To Mammography Screening Access Among Low-Income Women In The United States—A Scoping Review, Julia Messerman, Callia Nickels, Nigel C. James

Health Studies Faculty Publications

Despite the recognized importance of early detection, disparities in mammography access persist among low-income women in the United States. While financial barriers are often emphasized, less is known about how multiple barriers interact to shape access to screening. We conducted a scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines to synthesize evidence on barriers to mammography access among low-income women in the United States. A systematic search of PubMed, CINAHL, and Google Scholar identified peer-reviewed studies published between 2010 and 2025, of which 47 met inclusion criteria. Extracted barriers were categorized into …

Increasing Postpartum Appointment Attendance Rates, Tanya Lister

Doctor of Nursing Practice Posters and Presentations

Background: Postpartum visits provide an opportunity to detect and address potential complications, monitor healing and recovery, and offer guidance and support during the transition into motherhood. Current research shows that appointment reminders increase healthcare appointment attendance rates, whether delivered via text messages or phone calls.

Purpose: The purpose of this academic project was to plan, implement, and evaluate a process change within a single health facility to increase postpartum visit attendance rates.

Methods: This evidence-based scholarly project used telephone calls to remind patients scheduled for postpartum visits of their appointment dates and times. Appointment reminder phone calls were completed the …

A Perfect Storm In Advanced Aids: Severe Acute Respiratory Distress Syndrome From Pneumocystis Jirovecii And Mycobacterium Avium Complex Coinfection, Abdel Martinez, Abelardo Rodriguez, Conrad Chouinard, Fatimah Bello

School of Medicine Publications

Advanced HIV infection is associated with profound immunosuppression, predisposing patients to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) and Mycobacterium avium complex (MAC). PJP can cause severe respiratory disease, including acute respiratory distress syndrome (ARDS), while disseminated MAC may contribute to systemic illness and pulmonary complications. Concurrent infection with both pathogens is uncommon but may precipitate severe pulmonary failure. A man in his 40s presented with unintentional weight loss, fatigue, oral thrush, and progressive dyspnea. On arrival, oxygen saturation was 86% on room air, requiring high-flow nasal cannula. Laboratory evaluation revealed profound immunosuppression (CD4 7 cells/mm3, HIV RNA 123,000 …

Cracking The Code: The Systematic Development Of A Coding Matrix For Qualitative Data Analysis, Greta Gray, Marie-Christine Potvin

Department of Occupational Therapy Faculty Papers

A systematic approach was used to develop a coding matrix for a qualitative study with the intent to strengthen the credibility and dependability of the findings. Coding matrixes are commonly used in qualitative studies to organize data into meaningful units of text to be interpreted by the researchers. Current methods of coding matrix development can be problematic as they may introduce biases in the results and have limited reproducibility. A novel approach was employed to address this need with the “a priori” development of a coding matrix using a multi-step deductive and inductive process with multi-coders (n=5).  The coders who …

Intermembrane Coupling Between Bcl-Xl And The Ip3 Receptor Supports Local Ca2+ Transfer At Er-Mitochondrial Contacts, Arijita Ghosh, David Weaver, Chi Li, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Bcl-xL, an anti-apoptotic Bcl-2 family protein, engages laterally with Bak/Bax in the outer mitochondrial membrane (OMM) to inhibit apoptosis and interacts with the IP₃ receptor Ca²⁺ channels (IP3Rs) in the endoplasmic reticulum (ER) membrane to control Ca²⁺ release. It is unknown if OMM-localized Bcl-xL can also interact in trans with IP3Rs at ER-mitochondrial contacts to form a tethering complex that supports IP3R-mediated local Ca²⁺ transfer from ER to mitochondria. We establish that IP3R-mitochondria Ca²⁺ signal propagation depends on Bcl-xL. By targeting Bcl-xL specifically to different subcellular compartments, we find that OMM-localized Bcl-xL increases the efficacy …

Loss Of Pleasure (Anhedonia): A Sex-Dependent, Cross-Species Consequence Of Unpredictable Signals To The Perinatal Brain, Anna M. Zhou, Madison R. Tetzlaff, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Tallie Z. Baram, Elysia Poggi Davis

Psychology Faculty Articles and Research

Reward seeking is an essential component of human behavior. Anhedonia (reduced motivation for and pleasure in reward) is a core feature of several mental illnesses. Early life adversity associates with later impairments in reward behaviors and related psychopathology; however, specific aspects of early adversity that lead to disrupted reward behaviors are unknown. Capitalizing on evidence that unpredictable signals to the developing brain constitute adversity and influence neurodevelopment, we examined whether exposure to perinatal unpredictable maternal signals associated with diminished reward responsivity, and probed causality using experiments in mice. We analyzed a longitudinal human study (N=158 mother/child dyads) and a …

"It Doesn't Matter Where Ocd Comes From," Or Does It?, Caitlin M Pinciotti, Ryan J Mccarty, Gabriella T Ponzini

Faculty, Staff and Students Publications

Purpose of review: This review critically evaluates the claim that etiology is not relevant to cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). Research on the clinical presentation and treatment outcomes associated with traumatic/stressor and biological etiologies is presented.

Recent findings: The extant literature demonstrates varying clinical utility across the reviewed etiologies. Traumatic/stressor etiologies show the most consistent and robust evidence of clinical utility, demonstrating compelling associations with clinical presentation and treatment outcomes, while also being amenable to existing evidence-based approaches. Medical conditions (e.g., Pediatric Acute onset Neuropsychiatric Syndrome) and neurobiological factors also demonstrate considerable associations with OCD presentation, yet …

Environmental Exposure Risk Education To Enhance Chronic Kidney Disease Prevention And Screening For Nurse Practitioners, Kelsea J. Carrier

Doctor of Nursing Practice Posters and Presentations

Chronic kidney disease (CKD) affects approximately 36 million adults in the United States, with nearly 90% of individuals unaware of their diagnosis until advanced stages. While diabetes and hypertension remain the primary causes, increasing evidence highlights environmental exposures as significant and underrecognized contributors to CKD onset and progression. Exposures such as heavy metals, per- and polyfluoroalkyl substances (PFAS), air and water pollution, microplastics, and heat exposure have been linked to impaired renal function. Despite this growing body of evidence, environmental health content remains limited in nursing education, resulting in gaps in environmental health literacy (EHL) among nurse practitioners (NPs) and …

Standardizing Safe Sleep Education In An Outpatient Pediatric Cardiology Clinic: A Quality Improvement Initiative, Casey Hrbacek

Doctor of Nursing Practice Final Project Abstract

Purpose: This quality improvement (QI) project aimed to increase the reliability of standardized, evidence-based safe sleep education for caregivers of infants aged 0–12 months in an outpatient pediatric cardiology clinic within an academic health system

Background: Sleep-related death is the leading cause of death among infants aged 1-11 months and the third leading cause of infant mortality overall and is closely associated with modifiable unsafe sleep practices. Safe sleep education is delivered inconsistently across settings, particularly during the hospital-to-home transition for infants with complex cardiac disease.

Methodology: A caregiver-completed Safe Sleep Screening Checklist was embedded into clinic workflow. A medical …

Spae: Deciphering Cell Cycle Dynamics And Cell States In Single-Cell Rna-Seq Data, Jiahao Yi, Jiajia Liu, Peng Guo, Yuan-Nong Ye, Xiaobo Zhou

Faculty, Staff and Student Publications

Rapid advances in single-cell RNA sequencing (scRNA-seq) technology have enabled the investigation of gene expression changes at the single-cell level, particularly for elucidating the heterogeneity among cells and complex biological processes. This technique reveals subtle molecular differences within individual cells, thereby offering a unique viewpoint for the investigation of cell cycle progression, cellular differentiation, and disease pathogenesis. However, accurately identifying and analyzing cell cycle dynamics in scRNA-seq data remains challenging due to the complexity of the data and the subtle differences between cell states. To address this challenge, we developed the integrated Sinusoidal and Piecewise AutoEncoder (SPAE), an autoencoder-based piecewise …

Bridging The Gap In Science Research: Preparing Students For College- Level Research In The Sciences, Victoria Helwig, Yaoguang Li

UConn Library Presentations

Many first-year students enter college unprepared to fully engage with scientific literature and academic library resources. Drawing on experiences from academic librarians working with STEM students, this session explores common gaps in science research skills, including navigating databases, identifying scholarly sources, and understanding the structure of scientific literature. Participants will be introduced to practical strategies and classroom-ready activities to better prepare students for college-level research. Discussion questions: What science research skills do students struggle with most when entering college? How can high school instruction better support these skills? Where can librarians and educators collaborate to support student success?

Supporting Recovery: Intersections Of Health, Belonging, And Help Seeking After A Campus Mass Casualty Event, Sharon Jalene, Jason A. Ciccotelli, Lauren Gatto, Christian Ison, James Carbajal, Andrew Hooyman

Physical Therapy Faculty Articles and Research

Mass casualty events (MCE), such as campus shootings, can severely impact the mental health of students, faculty, and staff. This study examined the psychological effects of an MCE at a minority-serving institution and explored how sense of belonging, cardiorespiratory fitness, and treatment preferences influenced recovery. To measure the impact of the MCE on mental health an anonymous survey was administered four to five months post-MCE to university students, faculty and staff. Within the survey, participants were asked to retrospectively report their depression (PHQ-9) and anxiety (GAD-7) symptoms as they recalled them two weeks prior to the MCE, and as they …

Comment On: Managing Sickle Cell Disease And Related Complications In Pregnancy: Results Of An International Delphi Panel, Deva Sharma, Ilknur Pamuk, Kenneth I. Ataga, Alexandra Benachi, Selim Büyükkurt, Sophie Lanzkron, Hakan Ozdogu, Shivan Pancham, Lydia H. Pecker, Susan E. Robinson, Safak Yilmaz Baran

Cardeza Foundation for Hematologic Research

Consensus-based recommendations on managing sickle cell disease in pregnancy were recently published in a hematology journal. As this topic is also of great interest to obstetricians and gynecologists, we summarize some of these recommendations, while highlighting the challenges of providing evidence-based medical care to pregnant individuals with sickle cell disease.

"It's Probably Like A Web": Complex Relationships Between Pain And Mental Health Among Bisexual+ Women With Chronic Pain, Aster Harrison, Mansha Mirza

Department of Occupational Therapy Faculty Papers

INTRODUCTION: Bisexual+ women experience higher rates of both mental illness and chronic pain when compared to either straight or lesbian women. Their experiences of the relationship between their mental health and chronic pain remain underexplored. This article presents an intersectional Interpretive Phenomenological Analysis of the experiences of six bisexual+ women with chronic pain.

METHODS: Each woman completed two semi-structured interviews. Interviews were analyzed with Interpretive Phenomenological Analysis, beginning with in-depth case study analysis of each person's interviews before moving to comparison across cases.

RESULTS: Results indicated a complex web of multidirectional relationships between mental health and chronic pain. These relationships …

Acute Opioid Responses Are Modulated By Dynamic Interactions Of Oprm1 And Fgf12, Paige M Lemen, Alexander S Hatoum, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

We generated time-series data for 105 morphine- and naloxone-related traits across ~700 BXD mice (64 diverse strains for both sexes) for 3 hr after a single morphine injection. Variations in responses were mapped using genome sequencing-based genotypes. The locomotor responses to morphine mapped to the µ opioid receptor gene (

Mitigating Cancer Therapy-Related Cognitive Impairment By Targeted Activation Of Undruggable Phosphatase., Zhimeng Yao, Yuhua Meng, Huanyi Li, Yinhui Jiang, Xiaona Lin, Mengyuan Hu, Qing Liu, Xiaofu Qiu, Hongzheng Ren, Yunlong Pan, Bin Pan, Zexiong Guo, Shuyao Zhang, Dianzheng Zhang, Li Yang, Shegan Gao, Weijing Deng, Jianfan Chen, Hao Zhang

PCOM Scholarly Works

Cancer therapy-related cognitive impairment (CTRCI) is a debilitating neurotoxic condition adversely impacting cancer patients during and post-cancer treatments. The cancer treatments linked to CTRCI include chemotherapy, hormone therapy, targeted therapy, and immunotherapy. Despite CTRCI severely affecting the psychological and social, cognitive functions, and the overall quality of life of cancer survivors, no effective medications are available currently. Our prior studies have indicated hippocampal tyrosine phosphatase protein tyrosine phosphatase receptor type O (PTPRO) as a putative target for CTRCI. However, phosphatase is historically considered undruggable, and delivering drugs across the blood-brain barrier (BBB) is challenging. Here, we developed a novel delivery …

Clinicopathologic Spectrum Of Renal Disease In Sars-Cov-2 Infection And Post-Covid-19 Vaccination, Naya Williams, Mohammed S. Razzaque

School of Medicine Publications

Both SARS-CoV-2 infection and COVID-19 vaccination have been associated with renal complications. In the context of SARS-CoV-2 infection, kidney injury is primarily attributed to a complex interplay of systemic immune dysregulation and vascular damage. Severe infection triggers a cytokine-mediated inflammatory response characterized by elevated levels of pro-inflammatory mediators, resulting in systemic hemodynamic instability, increased capillary permeability, and renal hypoperfusion, ultimately leading to acute tubular injury. In addition, virus-induced endothelial activation promotes a prothrombotic state, microvascular injury, and further impairment of renal perfusion. Collectively, these processes converge to produce acute kidney injury (AKI) and, in severe or prolonged cases, may contribute …

Notch Signaling Regulates The Secretion Of Pro-Metastatic Factors In Extracellular Vesicles In Liposarcoma, Menchus Quan, Yi-Kai Liu, Ying Zhao, Madeline Kay, Kai Sun, Timothy P Gavin, Raphael E Pollock, W Andy Tao, Shihuan Kuang

The Brown Foundation: Institute of Molecular Medicine

Notch signaling is an emerging regulator of liposarcoma (LPS), but its role in mediating communication with the tumor microenvironment (TME) is unclear. Here, we investigate how Notch activation (NICD overexpression) alters the proteomes of LPS-derived extracellular vesicles (EVs). We used quantitative mass spectrometry to profile the EV proteome in multiple contexts: cultured LPS cells, LPS tumor, circulating EVs of LPS-bearing mice, and human LPS samples. We found that Notch signaling increases the secretion of EV proteins that favor tumor progression and metastasis but suppresses immune responses in murine LPS cells. Overlapping murine and human LPS data identifies 18 proteins that …

Ophthoevidence Report: Comparative Effects Of Prophylactic Strategies For Post-Intravitreal Injection Endophthalmitis: Protocol For A Systematic Review And Network Meta-Analysis, Maryam Ghadimi, Dena Zeraatkar, João Pedro Lima, Jinhui Ma, Sunir J. Garg, Peter Kaiser, David Steel, Tien Yin Wong, Sobha Sivaprasad, Charles Wykoff, Varun Chaudhary

Wills Eye Hospital Papers

BACKGROUND: Endophthalmitis is a rare but serious complication of intravitreal injections (IVI). To mitigate the risk of post-injection endophthalmitis (PIE), retinal specialists use different strategies, combining various prophylactic measures. However, existing systematic reviews have evaluated the effects of these measures in isolation, which does not consider their concurrent use in practice. A trustworthy systematic review with network meta-analysis (NMA) by providing a framework for simultaneous comparisons of different prophylactic combinations is essential to guide decision-making.

OBJECTIVES: To present a protocol for addressing the comparative effects of different strategies for the prevention of PIE.

METHODS: We will search Medline, EMBASE, Cochrane …

Civilian Threat Reduces Distance Perceptions And Officer Punishment In Police Use-Of-Force Encounters, Stephanie A. Cárdenas, Kristyn A. Jones, Yael Granot, Emily Balcetis

Psychology: Faculty Publications

People turn to video evidence to make judgments about the justifiability of an officer’s actions in use-of-force incidents. Despite beliefs that video offers an objective account of events, use-of-force footage elicits different judgments among those watching it. Across four experiments (Ntotal = 2615), we investigated whether discrepant punishment judgments arise in part because of differences in perceptions of the physical space that separates an officer and civilian. We focus on third-party observers’ subjective perceptions, as they shape public discourse and justice outcomes, influence institutional accountability, and fuel public response. Despite watching the same video, civilians appeared physically closer to officers …

Metastatic Large Cell Neuroendocrine Carcinoma: A Rare Cause Of Hypopituitarism, Smriti Nair, Taskeen Ahmed, Jessica Watari

Division of Internal Medicine Faculty Papers & Presentations

Pituitary metastases from pulmonary large cell neuroendocrine carcinoma (LCNEC) are exceedingly rare but should be considered in patients presenting with arginine vasopressin deficiency and panhypopituitarism in the context of known or suspected metastatic lung cancer. Early recognition and prompt initiation of hormonal replacement therapy are essential to prevent life-threatening endocrine crises and to improve symptom burden. We describe a case of a 43-year-old male who presented with dyspnea, weight loss, and weakness who was found to have metastatic LCNEC involving the liver. Endocrine evaluation revealed central hypothyroidism, central adrenal insufficiency, and later arginine vasopressin deficiency manifested by polyuria and hypernatremia. …

Myeloid Mmp14 Couples Extracellular Proteolysis To Inflammatory And Metabolic Remodeling During Obesity, Long J Shao, Fathima Elizondo, Feng Gao, Elizabeth L Lieu, Bharati Reddi, Maryam Elizondo, Iqbal Mahmud, Kristin Eckel-Mahan, Philipp E Scherer, Xin Ge, Huaizhu Wu, Sean Hartig, Kai Sun

The Brown Foundation: Institute of Molecular Medicine

Macrophages orchestrate tissue remodeling, inflammation, and metabolic dysfunction in obesity, but the role of macrophage-intrinsic extracellular proteolysis in immunometabolic regulation remains unclear. Matrix metalloproteinase-14 (MMP14), a membrane-bound protease, is strongly induced during monocyte-to-macrophage differentiation and further elevated in adipose tissue macrophages from high-fat diet (HFD)-fed mice. Pharmacological inhibition or myeloid-specific deletion of Mmp14 impaired macrophage differentiation, proliferation, migration, phagocytosis, and inflammatory activation in response to obesity-associated adipose tissue signals. Mechanistically, MMP14 promoted inflammatory programming by increasing endotrophin generation and enhancing TLR4-NFκB signaling. MMP14 also reprogrammed macrophage lipid metabolism by suppressing lipolysis and promoting lipid accumulation, altering metabolic communication with neighboring …