Digital Commons Network^™

Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu

Faculty, Staff and Students Publications

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in …

Ogg1s326c Variant Frequent In Human Populations Facilitates Inflammatory Responses Due To Its Extended Interaction With Dna Substrate, Jinling Han, Meichen Zhang, Jiakun Ge, Zhihua Ji, Jianyi Zhao, Yinchao Hu, Chunshuang Li, Yaoyao Xue, Xining Li, Haiwang Zhao, Zixu Cui, Miaomiao Tian, Xu Zheng, Dapeng Wang, Jing Wang, Min Wei, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba

Faculty, Staff and Student Publications

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1^S326C, prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1^S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1^S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but …

Loss Of Progesterone Receptor In Smooth Muscle Cells Has No Impact On Oviductal Contractions And Preimplantation Embryo Development†, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Cayce N Rose, John P Lydon, Wipawee Winuthayanon

Faculty, Staff and Students Publications

No abstract provided.

Disruption Of Oocyte Sumoylation Impacts Critical Regulatory Processes During Folliculogenesis In Mice, Zian Liao, Tessa E Steenwinkel, Bruno Moscoso, Ernesto Salas, Bethany K Patton, Amanda Rodriguez, Anna Malovannaya, Stephanie A Pangas

Faculty, Staff and Students Publications

The conjugation of small ubiquitin-like modifiers (SUMO) to target proteins, known as SUMOylation, plays a crucial role in regulating protein homeostasis, activity, interaction with other proteins, and subcellular localization. Loss of SUMOylation in nongrowing oocytes by conditional deletion of the E2 SUMO conjugating enzyme, Ube2i, at the primordial follicle stage leads to female sterility due to complex changes in oocyte development, including altered folliculogenesis, defective meiotic progression, and premature loss of the ovarian reserve. In this study, proteomics was used to compare control and Ube2i conditional knockout ovaries during the first wave of folliculogenesis to identify key differences that may …

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B Graf, Yuriko Katsumata, Jessica J Moorleghen, Chen Zhang, Yanming Li, Scott A Lemaire, Ying H Shen, Hong S Lu, Alan Daugherty, Hisashi Sawada

Faculty, Staff and Students Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

Impact Of Prior Exposures On Biomarkers Of Blast During Military Tactical Training, Zhaoyu Wang, Shengnan Sun, Alis Aksar Kranfli, Jeffrey Nemes, Molly J. Sullan, Andrew J. Hoisington, Lisa A. Brenner, Miciej Skotak, Christina R. Lavalle, Yongchao Ge, Walter Carr, Fatemah Haghighi

Faculty Publications

Blast injuries and subclinical effects are of significant concern among those Service Members (SMs) participating in military operations and tactical trainings. Studies of SMs repeatedly exposed during training find concussion-like symptomology with transient decrements in neurocognitive performance, and alterations in blood biomarkers. How prior mild TBI (mTBI) history interacts with low-level blast (LLB) exposure, however, remains unexplored, which we investigate in the present study, to identify interindividual biomarker changes from LLB exposures influenced by prior history of mTBI.

Optimal Diagnostic Strategies For Concussion-Related Vision Disorders: A Review, Iniya K. Adhan, Kammi B. Gunton

Wills Eye Hospital Papers

Concussions are a mild form of traumatic brain injury (TBI) that is typically self-limited and transient with a high prevalence within our communities. Due to the vast visual network interconnectivity, visual symptoms secondary to a concussion occur about 90% of the time. A gold standard to confirm concussion acutely has not been well established. Visual function testing based on symptoms remains the standard of care in off-site evaluation for diagnosis of oculomotor dysfunction. This review covers the current diagnostic strategies for vision based disorders post-concussion for sideline testing, off-site testing, and research driven testing.

Intouch Week Of May 12, 2025, New York Medical College

InTouch

• Commencement Speakers Set to Inspire Class of 2025
• Students Express Gratitude to Their First Patients During Convocation of Thanks
• Harnessing Digital Innovations in Ophthalmic Surgery
• TCDM Hosts Sixth Annual Convocation and Induction Ceremony
• TCDM’s Fourth Annual Research Day and Poster Competition Recognizes Student Researchers and Faculty Mentors
• Student Spotlight: Lynne MacFadyen Aspires to Help Others Find Their Voice
• Student Spotlight: Callie Hollander Finds Her Rhythm in Neuroscience Research

Risk Of Coronary Obstruction In Redo-Transcatheter Aortic Valve Replacement Between Bicuspid And Tricuspid Aortic Valves, Atsushi Okada, Syed Zaid, Miho Fukui, Evan Walser-Kuntz, Larissa I Stanberry, Marcus R Burns, John R Lesser, João L Cavalcante, Paul Sorajja, Vinayak N Bapat

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve replacement (TAVR) is approved across all risk profiles, including patients with bicuspid aortic valves. These patients are generally younger, with a higher chance of reintervention.

Objectives: The aim of this study was to compare the feasibility of redo transcatheter aortic valve (TAV) between bicuspid and tricuspid aortic valves.

Methods: A computed tomographic (CT) simulation of redo-TAV was conducted using 913 post-TAVR CT studies from patients who underwent TAVR with SAPIEN 3 or SAPIEN 3 Ultra (S3; n = 623) or Evolut R, Evolut PRO, or Evolut PRO+ (Evolut; n = 290) valves. Fifty-nine cases were for …

Ultrasound-Guided Sciatic And Femoral Nerve Block For Perioperative Pain Management In A Thai Crossbreed Dog Undergoing Tibial Plateau Leveling Osteotomy (Tplo): A Case Report, Wutti Bunjerdsuwan, Sirirat Niyom

The Thai Journal of Veterinary Medicine

This case report presents the use of ultrasound-guided sciatic and femoral nerve blocks as an alternative analgesic technique for perioperative pain control in a Thai crossbreed dog undergoing left tibial plateau leveling osteotomy (TPLO). The orthopedic examination revealed a 4/5 left hindlimb lameness score, with positive results on both the tibial compression test (TCT) and cranial drawer test (CDT). Radiographic evaluation showed the absence of a fat pad sign and osteophyte formation around the left stifle joint. A definitive diagnosis of left cranial cruciate ligament rupture (CCLR) was made. The dog underwent CCLR correction via TPLO, with perioperative pain managed …

Covid-19 And Related Adverse Neurological Complications, Hannah A. Wasson

Honors Thesis

Abstract

The COVID-19 pandemic changed the world drastically, and its impact was monumental. COVID-19 or SARS-CoV-2, or severe acute respiratory syndrome, was the virus responsible for causing such mayhem. This contagious virus can enter the body via different routes, live on surfaces for hours, and be transmitted through the air, increasing infection risk. Once it enters the body, it can trick the body into replicating the virus. From this reaction within the body, signs and symptoms follow. While the name indicates a respiratory illness, the virus can inflict injury on other parts of the body. Due to the organ systems …

Pterygopalatine Ganglion Blocks In Medicine: Bridging Neuromodulation And Pain Relief, Tori B. Ostrand

Honors Thesis

Chronic pain affects millions of individuals worldwide, presenting as a multifactorial condition that impacts physical, emotional, and socioeconomic well-being. Despite the availability of both pharmacological and non-pharmacological therapies, significant side effects, limited efficacy, and addiction risks drive the need for new, innovative treatments. The pterygopalatine ganglion block (PPGB) is emerging as a promising interventional approach that targets autonomic and neurogenic pathways that may be implicated in chronic pain mechanisms. This thesis reviews the neuroanatomy of the pterygopalatine ganglion, its potential role in autonomic regulation and pain mediation, and its clinical applications in treating headache syndromes such as cluster headaches and …

Exploring The Landscape Of Animal Advocacy In Egypt: Insights Into Stray, Wildlife, And Farmed Animal Rights, Yara Moussa, Wasseem Emam

General - Animal Protection

This article examines the landscape of animal advocacy in Egypt, a nascent and growing field in one of Africa’s largest economies and most densely populated countries. It focuses on three types of animal advocacy: 1) stray animal welfare, 2) wildlife conservation, and 3) farmed animal welfare. The paper critically analyses current practices and trends in each of these areas, highlighting the main challenges and opportunities facing the growth of the movement. Our research draws on insights from interviews with active animal welfare organizations, situating their practical experiences, daily operational struggles, as well as instances of success, within Egypt’s wider socio-economic …

Relationship Between Maternal Plasma Retinol And Provitamin A Carotenoids With Fetal And Infant Kidney Development, Anum Akbar

Theses & Dissertations

Vitamin A plays a critical role in fetal organ development. Studies suggest that maternal vitamin A deficiency affects fetal nephron numbers, potentially leading to smaller kidney sizes and an increased risk of chronic kidney disease later in life. However, human studies exploring maternal vitamin A's impact on fetal kidney development lack longitudinal data and within-cohort comparisons. Furthermore, the influence of provitamin A carotenoids (α-carotene, β-carotene, β-cryptoxanthin) on kidney size remains unexplored. This dissertation addresses these gaps by analyzing relationships between maternal and cord plasma retinol and provitamin A carotenoid concentrations with fetal and infant kidney sizes. Our prospective cohort …

Navigating Lipid Nanoparticle Design: From Microfluidic Optimization For Rna Delivery In Pancreatic Cancer To Extended-Release Formulations For Hiv-1 Therapy., Farhana Islam

Theses & Dissertations

Lipid nanoparticles (LNPs) have emerged as a powerful platform for the delivery of RNA and small-molecule therapeutics, enabling improved drug stability, biodistribution, and cellular uptake. This study explores the formulation and optimization of LNPs for two distinct therapeutic applications: (1) mRNA-based therapy for pancreatic cancer (PC) and (2) extended-action fostemsavir (FTR) delivery for HIV-1 treatment. For PC therapy, a library of 48 mRNA-LNP formulations was developed for intraperitoneal (IP) administration in an orthotopic pancreatic tumor mouse model. Using microfluidic assembly, LNPs were engineered with varying lipid compositions and characterized based on size, zeta potential, and cytotoxicity. Biodistribution and mRNA expression …

Cholestasis And Fluid Flow Are Biomechanic Regulators Of Cholangiocarcinoma Progression, Andrew Oleksijew

Theses & Dissertations

Cholestasis, altered or absent bile flow, is associated with poor survival in patients with cholangiocarcinoma, an aggressive cancer of the biliary epithelium. Changes in bile flow often result in stricture or obstruction. Experimental cholestasis promoted tumor growth and progression. However, studies are needed that directly assess the mechanical interaction between bile flow, or bile shear stress, and cholangiocarcinoma signaling. We hypothesized that cholestasis and absent bile shear stress activated cancer signaling and increased aggressive cellular behaviors such as proliferation and migration. Fluid shear stress approximating bile flow was applied by orbital culture plate method and compared to identical static culture …

Neurodegenerative Disease Mechanisms: Mitochondrial Impairment, Tau Aggregation, And Neuroinflammation As Central Drivers Of Disease Progression, Luis D. Estrella

Theses & Dissertations

The study of the intricate molecular mechanisms behind the pathology of neurodegenerative diseases has become a primary research area in the past decades. The major branches of these studies involve both disease progression and disease pathogenesis, in which neuroscientists have studied, and continue to study, the role that mitochondrial dysfunction, aberrant protein aggregation (like Tau), and immune cell reactions have on these. However, more recent studies have shined light to the fact that these three pathological features are not independent from one another and that their synchronous contributions may be the ultimate driver of neurodegeneration. This dissertation encompasses four different …

Evaluating The Therapeutic Potential Of Geranylgeranyl Diphosphate Synthase Inhibitor, Ram2061, In Myeloma Bone Disease, Molly Muehlebach

Theses & Dissertations

Multiple myeloma (MM) is a hematological malignancy of the plasma cells which often results in lytic bone disease. Myeloma bone disease (MBD), characterized by diffuse osteopenia, bone lesions, or pathological fracture, results from MM mediated promotion of osteoclast resorption and dual inhibition of bone formation, drastically reducing bone strength and integrity. Development of MBD is known to significantly impact patient quality of life and increase risk of mortality. Considering that up to 80-95% of MM patients are expected to develop bone disease post-initial MM diagnosis, there is a significant need within this population for therapeutics which address both MM disease …

Multi-Parametric Quantitative Evaluation Of Murine Cervical Remodeling During Pregnancy And Postpartum, Yan Yan, Jose Galaz, Joshua Marvald, Tanzy Love, Steven Yellon, Nardhy Gomez-Lopez, Mohammad Mehrmohammadi

2020-Current year OA Pubs

Cervical remodeling during pregnancy is a critical process that, if untimely, can lead to complications such as preterm birth (PTB). This study introduces a novel multi-parametric approach combining non-invasive imaging modalities to quantify cervical tissue changes during pregnancy and postpartum in a murine model. By integrating ultrasound-based measurements of cervical length, photoacoustic imaging of the collagen-to-water ratio, and elastography for tissue elasticity alongside histological assessments, this method provides a comprehensive evaluation of cervical remodeling. The findings reveal that combining these parameters significantly improves the accuracy of gestational age prediction compared to individual measurements, with a tri-parametric model achieving 85.3% prediction …

Optimizing Peptide Nucleic Acid-Based Pretargeting For Enhanced Targeted Radionuclide Therapy, Mohamed Altai, Ábel Nagy, Pauline Granit, Wahed Zedan, Myriam Cerezo-Magaña, Julie Park, Katharina Lückerath, Susanne Geres, Marie Sydoff, Daniel L J Thorek, Kristina Westerlund, David Ulmert, Amelie Eriksson Karlström

2020-Current year OA Pubs

Radiolabeled targeting agents have emerged as valuable tools for the treatment of disseminated cancer. Monoclonal antibodies (mAbs) are widely employed as carriers for diagnostic and therapeutic radionuclides due to their exceptional specificity and affinity. However, their prolonged circulatory half-life can diminish diagnostic efficacy and increase radiation exposure to non-target tissues in therapeutic applications, resulting in dose-limiting toxicities. To overcome this limitation, pretargeting technologies emerge as promising strategies to enhance tumor-to-background ratio and reduce radiation exposure of healthy tissues. Our previous work introduced a pretargeting concept leveraging the specific interaction between two peptide nucleic acid (PNA) probes, HP1 and HP2, as …

Molecular Basis Of Trpv3 Channel Blockade By Intracellular Polyamines, Jingying Zhang, Peng Yuan, Colin G Nichols, Grigory Maksaev

2020-Current year OA Pubs

ThermoTRPV1-4 channels are involved in the regulation of multiple physiological processes, including thermo- and pain perception, thermoregulation, itch, and nociception and therefore tight control of their activity is a critical requirement for correct perception of noxious stimuli and pain. We previously reported a voltage-dependent inhibition of TRPV1-4 channels by intracellular polyamines that could be explained by high affinity spermine binding in, and passage through, the permeation path. Here, using electrophysiology and cryo-electron microscopy, we elucidate molecular details of TRPV3 blockade by endogenous spermine and its analog NASPM. We identify a high-affinity polyamine interaction site at the intracellular side of the …

Recombinant Interleukin-7 Treatment Of Refractory Refractory Mycobacterium Avium Complexlung Disease (Impulse-7): A Pilot Phase Ii, Single-Center, Randomized, Clinical Trial, Carlos Mejia-Chew, Andrej Spec, Andrew H Walton, Alina Ulezko Antonova, Alexandra Dram, Sanjeev Bhalla, Marco Colonna, Michel Morre, Richard Hotchkiss

2020-Current year OA Pubs

BACKGROUND: Nontuberculous mycobacteria disease is an emerging opportunistic infection that is often refractory to therapy. Interleukin 7 (IL-7) is a pleiotropic cytokine with broad-ranging effects that enhance immunity and augment monocyte/macrophage anti-

OBJECTIVES: This study evaluated IL-7 in patients with refractory

DESIGN: Prospective, single-center, randomized, study of IL-7 in patients with refractory MAC-LD.

METHODS: Randomization (two sets of 4 weekly IL-7 injections) was stratified based on the presence of pulmonary cavities. The primary outcome was sputum culture conversion to negative within 6 months. Exploratory outcomes included investigation of potential molecular mechanisms of immunosuppression via single-cell RNA sequencing (scRNA-seq).

RESULTS: Of …

Anti-Cancer Activity Of Marine-Derived Fucosylated Chondroitin Sulfates In Ovarian Cancer Cell Spheroid Formation And Notch Signaling Inhibition, Daniella Beiner

Honors Theses

Ovarian cancer is the deadliest gynecological malignancy, with high recurrence rates driven by chemotherapy-resistant cancer stem cells (CSCs). Current therapeutics targeting Notch signaling to inhibit CSC formation have yet to demonstrate clinical benefit and pose risk of gastrointestinal toxicities. Here, we report that treatment with fucosylated chondroitin sulfates (FucCS) inhibited Notch signaling activation and spheroid formation in OVCAR3 ovarian cancer cells. Sulfation and fucosylation were shown to be key structural requirements of this anti-cancer activity. Moreover, this inhibition was synergistic with suppression of Notch glycosylation by Radical Fringe knockout. Preliminary experiments to conjugate FucCS to a maleimide linker in preparation …

Opmed Seal: Engineering A Rapid-Response Biodegradable Device For Hemorrhage Control And Infection Prevention In Abdominal Trauma, Paula M. Cabrera, Wesley Stephen Murphy

Honors Theses

Abdominal gunshot wounds are amongst the deadliest injuries encountered in combat and remote emergency settings. For military medics and first responders, the challenge lies in controlling internal bleeding and preventing infection before patients can reach surgical care-often within a narrow window of time known as the “golden hour”. Currently available field treatments are either too slow, not designed for internal wounds, or fail to provide antimicrobial protection. To address this gap, our team developed OpMed Seal: a compact, dual-syringe delivery system that deploys a biodegradable, antibiotic-infused hydrogel directly into abdominal injuries. The system is designed for rapid hemorrhage control, localized …

The Endocannabinoid System's Influence And Modulation Of Nociception, Doreen M. Flannery

Honors Thesis

The anatomy and physiology of pain is a well-defined pathway where noxious stimuli is processed by different systems in the brain. The central research question of this review is how can we better understand the neurobiological effects pain has, and assess if there is therapeutic potential in using endocannabinoids to modulate these effects. Endocannabinoids are signaling molecules that play a key role at both the cellular and molecular level in modulating both acute and chronic pain by influencing different processes within each level that affect how the body responds to both internal and external stimuli. The endocannabinoid system is a …

From Vector To Consequence: Integrating Vector Surveillance, Environmental Drivers, And Public Health Impact Into Lyme Disease Risk Management, Kathleen E. Angell

Theses & Dissertations

Lyme disease is the most common vector-borne disease in North America. This dissertation examines (1) how crowd-sourced compares to active vector surveillance and whether they are associated with Lyme disease, (2) how ecological factors relate to tick abundance and whether they can predict high disease years, and (3) estimated health and economic burden of Lyme disease and savings when interventions are applied. Tick abundance data from active and passive surveillance were compared and tested for association with Lyme disease in the first aim. We found differences in tick life-stage, species, and seasonality. Tick observations were positively correlated with Lyme disease. …

Effects Of Acute Exercise On Cognition: Consideration Of Potential Moderators, Mary G. Jackson, Lucy Wilson, Mara Liston, Elizabeth Gaines, Mckenzie Cotten, Reese Carwile

Honors Theses

The present thesis aims to determine the effects, if any, of six potential moderators on the effects of acute moderate-intensity exercise on cognitive functioning. The modes of exercise undertaken by the participants included treadmill (Experiment 1) and stationary bike (Experiment 2) exercise. Participants in each experiment either exercised or rested for twenty minutes and then participated in either a memory recall task or cognitive functioning (“Stroop”) task. The bouts of either exercise or rest on the stationary bike were followed by a rest period during which the participant would be exposed to either standard air oxygen levels (normoxia) or hypoxic …

Schistosoma Haematobium Infection In Ethiopian Children: Evaluating Praziquantel Efficacy, Nutritional Effects, And Diagnosis Using Flukecatcher, Louis Fok

Theses & Dissertations

Urogenital schistosomiasis continues to impact the wellbeing of hundreds of millions of people worldwide and remains a significant public health challenge across Ethiopia. Despite existing knowledge on the disease, there remain significant unanswered questions with regard to its treatment and diagnosis. This dissertation evaluated the efficacy of praziquantel at treating urogenital schistosomiasis, improving nutritional parameters among children and the performance of FlukeCatcher at detecting and determining the intensity of infection. In effecting this, a total of 977 children aged 5 through 15 from the Afar and Gambella regions of Ethiopia were screened for S. haematobium infection using urine filtration microscopy …

Region-Specific Brain Targets Drive Circuit Formation And Maturation Of Human Retinal Ganglion Cells, Kang-Chieh Huang, Han-Yin Jeng, Qudrat Abdulwahab, Victoria R Cuevas, Eyad Shihabeddin, Claire Young, Melody Hernandez, Jason S Meyer, Nicholas M Tran, Melanie A Samuel

Faculty, Staff and Students Publications

Human vision relies on retinal ganglion cells (RGCs), and their connectivity with distinct brain regions enables higher order visual processing. RGCs vary considerably between species, and small model organisms display distinct RGC innervation patterns from that in humans. There is thus a need for robust models of human RGC circuit formation that preserves innervation specificity. Here, we developed an in vitro microfluidics eye-to-brain connectivity model using human pluripotent stem cell (hPSC)-derived RGCs to assess brain region-specific connectivity features. We find that cultured human RGCs segregate their dendrites and axons and display axonal features that align with that of their in …

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …