Digital Commons Network^™

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

Animal Models Of Aortic Aneurysm And Dissection: A Comparative Guide For Mechanism, Therapeutic Testing, And Translational Readouts, Shayan Mohammadmoradi, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Aortic aneurysms and dissections are devastating vascular diseases with high mortality, yet no pharmacological therapy has proven effective in halting growth or preventing rupture. Surgical and endovascular repair remain the only treatment options for advanced disease. Animal models have been indispensable in defining mechanisms and testing candidate therapies, but the diversity of protocols, strain-dependent variability, and heterogeneous endpoints complicate interpretation and translation. This review provides an update focused on how to match models to specific research questions. We critically compare commonly used abdominal aortic aneurysm (AAA) models (angiotensin II ± hyperlipidemia, elastase, calcium chloride, β-aminopropionitrile BAPN hybrids, and mineralocorticoid agonist/fludrocortisone …

Differences In Biologic Clinical Trials For Chronic Rhinosinusitis With Nasal Polyps—Are We Comparing Apples With Oranges?, Marjolein Cornet, Peter W. Hellings, Martin Desrosiers, Martin Wagenmann, Richard Follows, Laura Walrave, Luz Adriana Jimenez, Lee Tombs, Dawn Edwards, Peter Howarth, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

In recent years, several biologics targeting Type 2 inflammation have been developed for treating chronic rhinosinusitis with nasal polyps (CRSwNP). These have been studied in registrational randomized controlled trials (RCTs), which vary in their patient populations, trial design, endpoints, geography, timing, or data-handling processes. While (in)direct treatment comparisons and meta-analyses have been carried out to compare efficacy results from RCTs, often these fail to properly account for these between-study differences. Here, we summarize the key between-study differences that can influence trial outcomes and highlight the resulting challenges faced when comparing outcomes from different Phase III RCTs of biologics in CRSwNP.

Dean's Update, January 2026, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

The Impact Of Gastric Sleeve And Roux-En-Y Gastric Bypass On Chief Cell Function And Protein Digestion In Obese Patients, Garikoitz Mikel Gainza

Honors Undergraduate Theses

Obesity has become one of the largest global health concerns of the 21^st century, correlating with numerous associated diseases. To help address the growing prevalence and burden of obesity, sleeve gastrectomy and Roux-en-Y gastric bypass have become two commonly performed surgical procedures done to promote weight loss by altering the anatomical structure of the stomach and surrounding organs of the gastrointestinal system. Although the benefits of improved metabolism linked to these surgical procedures are well studied, their impact on the physiology of gastric cells, and more specifically chief cells as they relate to protein digestion post-surgery, is yet to …

An Anti-Adhesive Compound Modulating The Production Of Staphylococcus Aureus Cell Wall-Anchored Proteins, Allison C. Leonard, Ruina Bao, Cindy Menjivar, Megan J. Myers, Telmo O. Paiva, Zhiyong Zheng, Kirsten A. Berry, Kenneth W. Bayles, Ronald S. Flannagan, Yves F. Dufrêne, Jeffrey L. Bose, David E. Heinrichs, Georgina Cox

Journal Articles: Pathology and Microbiology

As one of the leading global causes of death associated with antimicrobial resistance, Staphylococcus aureus frequently colonizes the human nasal cavity and adheres to keratinized skin, establishing reservoirs that drive subsequent infections and emphasize the need for new decolonization strategies. Using a high-throughput, whole-cell screening platform, here we identify geranylgeranoic acid (GGA), a naturally occurring polyunsaturated, branched-chain fatty acid, as having dual activity against methicillin-resistant S. aureus (MRSA). At elevated concentrations, GGA exhibits microbicidal effects, whereas at sub‑microbicidal doses, it effectively inhibits MRSA adhesion to keratin, fibronectin, fibrinogen, and immunoglobulins. GGA possesses anti-adhesive activity against a panel of multidrug-resistant S. …

What Is The Association Between Iron Deficiency Anemia And The Frequency Or Severity Of Febrile Seizures In Children Under The Age Of 5?, Rehab Fawzy Abdel Mohsen Soliman, Samar Mahmoud Ahmed, Yasmen Ahmed Said, Shaimaa Mohamed Hassan, Dalia Hassanin Hussin, Dina Gaber Soliman, Zeinab Abdalla Ali, Eman Farouk Osman

Journal of Medicine in Scientific Research

Background and Aim Febrile seizures (FS) are a common type of convulsion in young children and are frequently associated with fever in the absence of a central nervous system infection. This study aims to investigate the relationship between iron deficiency and febrile seizures, focusing on their occurrence, severity, and recurrence in children aged 6 months to 5 years. Methodology This study employed a case-control design and was conducted at El Sahel Teaching Hospital in Cairo, Egypt, over 12 months. The study sample consisted of 160 children, 80 of whom had febrile seizures and another 80 who were age- and sex-matched …

Transcortical Approach For Central Neurocytoma: Efficacy, Safety, And Functional Outcome, Eslam Abozied Kandil

Journal of Medicine in Scientific Research

Background Central neurocytoma (CN) is a rare intraventricular neuronal tumor that predominantly affects young adults and is frequently associated with obstructive hydrocephalus. Surgical resection remains the cornerstone of treatment, yet the optimal surgical corridor and predictors of long-term outcome remain debated. Objective To evaluate the efficacy, safety, functional outcomes, and oncological control of transcortical microsurgical resection for central neurocytoma at a single neurosurgical center. Methods A retrospective review was conducted of all patients undergoing transcortical resection of central neurocytoma between 2017 and 2025. Clinical presentation, radiological characteristics, surgical approach, extent of resection, cerebrospinal fluid (CSF) diversion, postoperative complications, functional outcomes, …

The Role Of Human Sarcosine Dehydrogenase And Endothelial Growth Factor In Early Diagnosis Of Cancer Prostate, Hala Ibrahim Mohamed, Amr Mohamed Mounier Elsofy

Journal of Medicine in Scientific Research

Background: As the second most common cancer in males, prostate cancer contributes significantly to cancer-related deaths. Prostate-specific antigen (PSA) test and digital rectal examinations are used to identify it, albeit PSA screenings frequently produce unreliable results. Initial symptoms may include sexual dysfunction and urinary problems. The standard diagnostic method is biopsies, which are carried out under the direction of ultrasound or magnetic resonance imaging (MRI). However, they are risky and can result in infections and erectile dysfunction, which emphasizes the need for better biomarkers. Sarcosine and vascular endothelial growth factor are important metabolites associated with the progression of prostate cancer, …

Role Of New-Onset Qt Prolongation In Ecg In Critically Ill Septic Patients As A Prognostic Tool: An Observational Prospective Cohort Icu Study, Talal Ibrahim Mostafa Hagag, Salwa M.A. Dahesh

Journal of Medicine in Scientific Research

Background QT interval prolongation is a common finding among critically ill patients and could be a marker of autonomic nervous dysregulation, instability of metabolism, and/or septic cardiomyopathy. Nevertheless, its prognostic role among septic ICU populations remains unclarified. The current aim of this study was to explore its potential role regarding short-term mortality. Methods In this cohort study, 119 septic adults were included in the study within 24 hours of ICU admission. Demographics, clinical variables, lab values, and QTc intervals were measured within 2 hours of ICU admission following exclusion for clinically significant electrolyte imbalances and use of QT-prolonging medications. QTc …

Bariatric Surgery Impacts Immune Cell Metabolism And Function Dependent On Metabolic Status, Samantha N. Hart

University of Kentucky Doctoral Dissertations

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with …

Facial Expression With Type Of Eye Opening Associates With Multi-Organ Failure: An Observational Prospective Icu Cohort Study, Talal Ibrahim Mostafa Hagag

Journal of Medicine in Scientific Research

Title Facial expression with the type of eye opening associates with multi-organ failure: an Observational prospective ICU cohort study Background Accurate prognostication in the intensive care unit (ICU) remains a challenging task. Conventional severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) quantify physiological derangement but overlook real-time neurological and affective responsiveness. Behavioral indicators—particularly facial expressivity and eye-opening response—may reflect cortical and brainstem integrity, offering a simple, non-invasive adjunct for bedside mortality prediction. Methods In this single-center, prospective observational study, 210 adult patients in the ICU were assessed within 24 hours of admission. Two blinded …

Are The Risks Of Asthma And Allergic Diseases In Children Born By Cesareansection (Cs) Influenced By Maternal Factors (E.G., Maternal Asthma, Diet, Antibiotic Use During Pregnancy)?, Rehab Fawzy Abdel Mohsen Soliman, Samar Mahmoud Ahmed, Yasmen Ahmed Said, Shaimaa Mohamed Hassan, Dalia Hassanin Hussin, Dina Gaber Soliman, Zeinab Abdalla Ali

Journal of Medicine in Scientific Research

Background and Aim The increase in the number of Cesarean Section deliveries (CS) in the world has triggered questions about the possible long-term health consequences for the children being delivered, particularly the chances of being affected by asthma and other allergic ailments. Some prior studies suggested that CS deliveries may negatively influence immune system development due to altered microbial colonization and an increased risk of respiratory morbidities. However, trying to separate the impact of delivery methods and the maternal as well as the surroundings is a hard nut to crack. The present study aims to establish whether maternal asthma, diet, …

Brain-Derived Extracellular Vesicles Potentially Mediate Crosstalk With Peripheral Organs In Neurodegenerative Diseases, Ramzi H. Hamdalla, Vibha B. Bhaskar, Changhai Tian

Toxicology and Cancer Biology Faculty Publications

Brain-Derived Extracellular vesicles (BDEVs) are emerging mediators of intra- and interorgan communication in neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). A growing body of evidence suggests that BDEVs play an important role in modulating intercellular communication within the central nervous system in the pathogenesis of many NDs. By transporting non-coding RNAs (e.g., miRNAs) and important pathological proteins, BDEVs also influence peripheral organs and contribute to the progression of disease in the central nervous system (CNS). This review extends the understanding of NDs beyond solely brain dysfunction and gives a novel framework for the progression of …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …

Endothelin-1 In The Failing Fontan: Pathobiology, Precision Therapeutics, And Future Trial Design, Iman Maiza

Department of Pediatrics Faculty Publications

The Fontan circulation, devised as definitive palliation for single-ventricle congenital heart disease, imposes systemic venous hypertension, loss of pulmonary arterial pulsatility, and restricted preload reserve. These hemodynamic trade-offs progressively injure the pulmonary vasculature, liver, and lymphatic system, producing late morbidities including elevated pulmonary vascular resistance, Fontan-associated liver disease (FALD), protein-losing enteropathy, and arrhythmias. Endothelin-1 (ET-1), a potent vasoconstrictor and profibrotic mediator, plausibly unifies these complications. Mechanistic studies demonstrate ET-1 upregulation in failed Fontan lungs, activating PLC–Ca²⁺, RhoA/ROCK, and MAPK/ERK cascades to drive vasoconstriction and remodeling. In cirrhotic livers, ET-1 localizes to stellate cells, promoting contraction and fibrogenesis, mechanisms biologically relevant …

Effect On C5 Myotome Distribution After Cervical Spinal Surgery: A Case Report On Early Neuromuscular Re-Education, Nicole Eder Asebias

Capstone Showcase

Background and Purpose: Postoperative C5 palsy is a known problem after cervical spinal surgery and is characterized by upper extremity weakness that can significantly limit the ability to perform daily tasks. Despite its clinical relevance, limited literature describes physical rehabilitation-focused interventions strategies for this condition. The purpose of this case report is to describe the presentation, physical therapy intervention, and outcomes of a patient with postoperative C5 palsy managed with neuromuscular re-education.

Case Description: The patient is an adult who developed left upper extremity weakness consistent with C5 palsy following cervical spinal surgery. Primary impairments included decreased shoulder abductor and …

The Connection Between Medicaid And Obesity In Northeast Ohio, Emmie Kelley, Sophie Kheder

Williams Honors College, Honors Research Projects

Obesity is a major public health concern in the United States that is projected to increase exponentially over the next few years. Obesity is commonly associated with a lower socioeconomic status. Lower-income individuals tend to be supported by Medicaid, a federal insurance program for low-income Americans. Prior studies have shown a positive correlation between income status and obesity prevalence. Our goal was to find if there was a correlation between Medicaid patients and obesity in Northeast Ohio, to provide physicians with a set of characteristics to better combat obesity, since preventative and treatment guidelines are tailored to national trends. We …

The Effects Of Habitual Temperature And Diet On Crayfish Physiological Processes, Tyler D. Deramo, Sunny Rana, Victor Popoviciu

Williams Honors College, Honors Research Projects

We will use crayfish to test the individual and combined effects of temperature and diet to see how they impact physiological processes such as metabolism, growth rate, molting patterns, and behavioral analysis. A total of forty-eight crayfish will be used throughout the experiment, and they will be housed in separate containers. A plant-based diet (consisting of fresh kale) and an animal-based diet (consisting of dried bloodworms) will be tested alongside room temperature (~18 degrees Celsius) and a warmer habitual temperature (~24 degrees Celsius). Metabolism will be measured via O2 consumption, and growth will be measured by weighing and measuring the …

Dysregulation Of Alternative Splicing Patterns In The Ovaries Of Reproductively Aged Mice, Adnan T. Alsamaraee, Vanessa L. Correll, Julius O. Nyalwidhe, Pavla Brachova, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Female reproductive aging is characterized by progressive deterioration of ovarian function, yet the molecular mechanisms driving these changes remain incompletely understood. Here, we used long-read direct RNA-sequencing to map transcript isoform changes in mouse ovaries across reproductive age. Comparing young and aged mice after controlled gonadotropin stimulation, we identified widespread alternative splicing changes, including shifts in exon usage, splice site selection, and transcript boundaries. Aged ovaries exhibited increased isoform diversity, favoring distal start and end sites, and a significant rise in exon skipping and intron retention events. Many of these age-biased splicing events altered open reading frames, introduced premature stop …

Sox11 Overexpression Restores Embryonic Pro-Growth Transcription In Mature Corticospinal Tract Neurons, Eliazbeth Batsel, Zimei Wang, Elizabeth Otten, Syed Roshan, Rabia Mohammad, Paula Pascual, Darby O'Shea, Jose Rosas, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Neurons in the central nervous system (CNS) display a high capacity for axon growth during early development but lose this ability at a pivotal differentiation stage marked by synaptic maturation, circuit integration, and a profound shift in gene transcription. Once mature, most CNS neurons fail to reverse this transcriptional switch after axon injury, fundamentally constraining their intrinsic capacity for axon regeneration. Here, we show with single-nucleus RNA sequencing that forced expression of the transcription factor Sox11 in mature corticospinal tract (CST) neurons produces large-scale and stable changes in gene expression that are highly enriched for growth-relevant processes, and which strongly …

A Randomized Controlled Trial In A Teaching Hospital Comparing The Outcomes Of ‎Single-Layer Versus Double-Layer Uterine Suturing With Polyglactin In The Development ‎Of Uterine Niche Following Caesarean Section, Ahmed A. Kassab, Ali E. Khayal

Journal of Medicine in Scientific Research

Background Caesarean section (CS) rates are rising globally, with Egypt reporting one of the highest rates. A potential complication of CS is the development of a uterine scar defect, or niche, which may be associated with abnormal bleeding, dysmenorrhea, and infertility. The technique of uterine closure may play a significant role in the prevention of niche formation. Aim To evaluate the effectiveness of double-layer uterine closure versus single-layer closure in preventing niche formation after a first CS, as assessed by transvaginal ultrasound (TVUS) at six weeks postpartum. Methods This randomized controlled trial was conducted at Mataryia Teaching Hospital, Cairo, including …

Age-Related Ultrastructural Differences In The Dorsal Cortex Of The Inferior Colliculus In The Fischer Brown Norway Rat, Kylee M. Tenney, Dakota Smallridge, Gillian Barach, Gurveer Singh, Erin Beskitt, Justine Busby, Syllissa Duncan, Alexa Wawrzyniak, Brenda Vega, Nick Tokar, Andrew Ohl, Jesse Young, Jeffrey Mellott

Williams Honors College, Honors Research Projects

The inferior colliculus is a nucleus in the auditory midbrain that plays an important role in sound and speech processing through how it encodes temporal precision. Temporal precision depends on the balance of inhibition and excitation within the IC. This balance degrades during aging. Age-related changes in synapses have been described in the lemniscal IC as a contributing factor for this imbalance. However, it is unknown if aging affects synapses throughout the non-lemniscal IC in a similar manner. We sought to determine this by examining the dorsal cortex of the IC. The ICd is a non-lemniscal nucleus that is well …

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Bodies Of Knowledge: The Accuracy Of Medical Anatomical Drawings From The 14th To The 18th Century, Marina G. Mitchell

Honors Undergraduate Theses

From the fourteenth to the eighteenth centuries, European anatomical illustration underwent major transformations in response to changing scientific methods, technologies, and visual conventions, reflecting critical transitions in anatomical history. Scientific evolution allowed these images to achieve increasing structural precision and internal detail, though they frequently diverged from anatomical forms as they are understood today. This study examines how anatomical inaccuracies across five centuries emerged not from ignorance, but from deliberate mediation between purpose, observation, pedagogy, artistic convention, and cultural ideology. Through close analysis of works in visual comparison to their modern counterparts, this thesis identifies specific deviations from the twenty-first …

Impact Of Senescence On Breast Cancer Outcomes, Gracie Sous

Honors Undergraduate Theses

Cellular senescence is a biological process in which damaged cells exit the cell cycle while remaining metabolically active and accumulating within tissues. Senescence plays a complex role in breast cancer progression, largely through the secretion of senescence-associated secretory phenotype (SASP) factors. These factors include a broad range of inflammatory cytokines, chemokines, and signaling molecules that can influence the tumor microenvironment.

Studies suggest that senescence may significantly promote cancer metastasis. Therefore, this study aims to investigate the genes involved in cancer progression and to improve understanding of how SASP is regulated, which is critical for improving breast cancer outcomes. The central …

A Bayesian Late-Fusion Supportability Framework For Rare-Disease Severity Prediction In Glut1 Deficiency Syndrome, Jordan M. Rodriguez

Mathematics Dissertations

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare neurometabolic disorder with heterogeneous neurological and developmental severity. Because patient-level severity is not observed as a single validated outcome, this dissertation develops a Bayesian late-fusion supportability framework for constructing and predicting an ordered latent severity phenotype from clinical, genetic, and EEG-derived evidence. The primary target was constructed in a larger clinical cohort using age-5 symptom burden and learning cognition, then assigned to an aligned multimodal prediction cohort. Target-defining variables were excluded from supervised predictors, and models were evaluated using patient-exclusive cross-validation with training-fold preprocessing and fold-wise EEG PCA.

The primary …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …