Digital Commons Network^™

A Community Effort To Develop Common Data Elements For Pre-Clinical Spinal Cord Injury Research., Britt A. Fedor, Abel Torres-Espin, Romana Vavrek, Maryann E. Martone, John L. Bixby, John C. Gensel, Vance Lemmon, Jeffrey S. Grethe, J. Russel Huie, Adam R. Ferguson, Karim Fouad, The Preclinical Sci Common Data Elements (Cde) Workshop Participants

Spinal Cord and Brain Injury Research Center Faculty Publications

For nearly 350 years, the process of disseminating scientific knowledge has remained largely unchanged. Scientists conduct experiments, analyze the data, and publish their findings in the form of scientific articles. Since the turn of the century, this process has been challenged by numerous open science and data sharing efforts to enhance transparency, reproducibility, and replicability of scientific research. Big data approaches, together with machine learning and artificial intelligence, are frequently used to gain insight into the ever-growing complexity of biological systems and biomedical research. To utilize these approaches and harness the continuously increasing computational power requires data to be both …

Cross-Species Comparisons Between Pigs And Mice Reveal Conserved Sex-Specific Intraspinal Inflammatory Responses After Spinal Cord Injury, Reena Kumari, Gabrielle V. Hammers, Robert H. Hammons, Andrew N. Stewart, Steven M. Maclean, Tracy Niedzielko, Lonnie E. Schneider, Candace L. Floyd, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

Objective Therapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model.

Methods Adult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury.

Results SCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing …

Exploring The Links Among Brain Iron Accumulation, Cognitive Performance, And Dietary Intake In Older Adults: A Longitudinal Mri Study, Valentinos Zachariou, Colleen A. Pappas, Christopher E. Bauer, Elayna R. Seago, Brian T. Gold

Neurology Faculty Publications

This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60–86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5–3.0 years later. Dietary intake was evaluated at baseline using a validated questionnaire. Cognitive performance was assessed at TP2 using the uniform data set (Version 3) neuropsychological tests of episodic memory (MEM) and executive function (EF). Voxel-wise, linear mixed-effects models, adjusted for longitudinal gray matter volume …

Circulating Molecular Drivers Of Bone Remodeling In Pancreatitis, Rachel L. Hill, Dhiraj Yadav, Phil A. Hart, David C. Whitcomb, Kristen J. Mcquerry, Kelsey N. Karnik, Kimberly M. Stello, Darwin L. Conwell, Madhumathi Rao

Internal Medicine Faculty Publications

INTRODUCTION: 

Pancreatitis-associated osteopathy is a clinically significant but mechanistically underexplored complication of pancreatic disease. We aimed to characterize stage-specific alterations in bone remodeling biomarkers across the spectrum of disease: recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP).

METHODS: 

In a cross-sectional analysis of North American Pancreatitis Study 2 participants, we measured serum mechanistic (sclerostin, dickkopf-1, receptor activator of nuclear factor κβ ligand, and osteoprotegerin), hormonal (fibroblast growth factor 23, insulin, and leptin), and modulatory (osteopontin, oncostatin, and osteoactivin) markers in controls (n = 30), RAP (n = 40), and CP (n = 40) using a multiplex assay. Group differences were …

Adverse Childhood Experiences, Depression And Subjective Cognitive Decline By Gender: A Moderated Mediation Analysis, Monique J. Brown, Darlingtina K. Esiaka, Jaya Viswanathan

Behavioral Science Faculty Publications

Studies assessing depression as a mediating factor between adverse childhood experiences (ACEs) and subjective cognitive decline (SCD) are lacking. Therefore, the aims of this study were to: (1) determine the mediating role of depression in the association between ACEs and SCD; and (2) assess the moderating role of gender. Data were obtained from the 2023 Behavioral Risk Factor Surveillance Study (BRFSS) survey (N = 38,600). Crude and adjusted path analyses were used to determine the mediating role of depression between ACEs and SCD. Adjusted analyses controlled for sociodemographic confounders. ACEs were positively associated with depression (B = 0.129, p …

Differential Speed And Accuracy Trade-Off In Working Memory Retrieval And Bilateral Precuneus Between Older Men And Women, Darlingtina K. Esiaka, Stephanie Strothkamp, Aghayeeabianeh Banafsheh, Lucas S. Broster, David K. Powell, Gregory Jicha, Yang Jiang

Behavioral Science Faculty Publications

Background

Despite various hypotheses, including differences in longevity, hormones, genetics, and neuroanatomy, the reasons for the higher prevalence of Alzheimer's disease in older women compared to men remain unclear. Emerging evidence suggests that the precuneus, a key region of the default mode network, is linked to internally focused processes like memory retrieval. We examined the relationship between precuneus volumes and task performance (accuracy and reaction time) during working memory retrievals in cognitively normal older adults.

Method

A cohort of older participants (N = 45; 25 women; M_age = 77) from the University of Kentucky Alzheimer's Disease Research Center …

Examining The Communication Work Of Women Who Have Tested Brca-Positive: “I Feel This Responsibility To Let People Know”, Summer C. Martin, Allison M. Scott, Anne M. Stone

Communication Faculty Publications

Inheriting a pathogenic variant in the BRCA1 or BRCA2 gene considerably increases a woman's risk levels for developing breast and ovarian cancer. In addition to serious physical health implications, women with a BRCA pathogenic variant may face psychosocial challenges, including those related to navigating the often demanding process of communicating about topics regarding BRCA with family and other social network members. Based on in-depth interviews with 24 women who tested BRCA-positive, we found that—consistent with the conceptualization of communication work articulated by Donovan-Kicken et al. (2012) as an extension of the theory of illness trajectories (Corbin & Strauss, 1988)—the labor …

Gut Microbiome, Neuroinflammation, And Fetal Alcohol Spectrum Disorders: Insights From Rodent Models, Abdulrahman M. Busayli, Wenhua Xu, Ghaidaa A. Raffah, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, …

Ceramide Homeostasis In Hepatic Lipid Droplets, Leobarda Robles-Martinez, Kylie H. Morin, Mariana Nikolova‑Karakashian

Physiology Faculty Publications

Almost all eukaryotic cells have the capacity to form lipid droplets (LDs) in conditions of excess energy. Traditionally thought to be just inert fat reservoirs, LDs have recently emerged as important metabolic regulators of cellular stress response that buffer excess free fats and protect cells from lipotoxicity. Ceramide is a bioactive lipid that accumulates in metabolic tissues during fat oversupply. Emerging evidence suggests that sphingolipids and sphingolipid-metabolizing enzymes are found in the LDs and affect LD biogenesis and functions. This article aims to summarize the evidence, delineate some plausible functions of ceramide in hepatic LD biogenesis, and illustrate some of …

Impact Of Fast Advancement And Early Fortification Of Enteral Feedings In Preterm Infants, A Retrospective, Observational Study., Enrique Gomez-Pomar, Holly Clarke, Jamie Adams

Pediatrics Faculty Publications

UNLABELLED: We aimed to evaluate the outcomes and growth of preterm infants at a Neonatal Intensive Care Unit that focuses on early initiation, fast advancement, and early fortification of enteral feeds.

METHODS: Retrospective study conducted at a community hospital level III NICU. Extensive feeding data and outcomes were collected by utilizing a NutritionIQ software application, NICUtrition®. Infants born between 26- and 34-weeks gestational age were included, whereas infants with congenital defects, deceased or with incomplete data were excluded. Frequency and descriptive statistical analysis were conducted using chi-square and Fisher's exact test. Unadjusted odds ratios were computed for categorical variables and …

Advances In Magnetic Nanoparticles For Molecular Medicine, Xiaoyue Yang, Sarah E. Kubican, Zhongchao Yi, Sheng Tong

Biomedical Engineering Faculty Publications

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular …

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer’S Disease Detection And Monitoring, Melissa E. Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah E. Pape, Juan Fortea, Nicholas J. Ashton, Chinedu Udeh-Momoh, Sid E. O’Bryant, Dwight German, Florin Despa, Mark Mapstone, Henrik Zetterberg

Neurology Faculty Publications

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer’s Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

Lgbt People's Sense Of Linked Fate: Belonging And Utility, Kay Hales

Theses and Dissertations--Political Science

This is a three study dissertation. While the LGBT community is often referred to as a monolith, research suggests that it may be separate subgroups under one umbrella. Linked fate is the sense that what happens to one member of a group will affect all other group members with consequences for political behavior. While research on racial identity groups suggests that members often feel a sense of linked fate with other group members, this research has not been generalized or explored in the LGBT community. This study empirically explores whether there is a sense of linked fate in the LGBT …

Bones And Brains: The Association Between Osteoporosis And Depression, Mason Taylor

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Introduction: Osteoporosis and depression are two public health problems that are increasing in prevalence. Previous studies have found a positive association between the two variables in women and men and women together, but there is a gap when looking at men. Therefore, it was important to investigate the odds of depression in men, women, and men and women together to make comparisons by sex.

Methods: 1,602 participants aged 65 and older were included in the study from the National Health and Nutrition Examination Survey (NHANES) 2017 – March 2020 Pre-Pandemic dataset. One unadjusted and seven adjusted models were created for …

Parental Stress, Self-Compassion, And Meaning In Life Among Mothers Of Children With Autism Spectrum Disorder, Hyun-Ju Ju

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Mothers of children with autism spectrum disorder (ASD) often experience higher levels of parenting stress than mothers of typically developing children or children with other developmental disabilities, which can undermine their psychological well-being. Additionally, parental stress among mothers of children with ASD is influenced by various demographic factors. This study primarily identified the relationship between parental stress and demographic factors. It also examined the correlations among parental stress, self-compassion, and meaning in life of mothers raising children with ASD within a positive psychology context. Finally, this study investigated whether self-compassion mediates the relationship between parenting stress and two distinct dimensions …

How Do Couples Of Autistic Children Perceive Their Quality Of Life? A Case Study Featuring Sequential Mixed Methodology, Amanda Duncan Dr.

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Families who have autistic children report significantly lower quality of life indicators than neurotypical families and those with other developmental disabilities (Bitsika & Sharpley, 2004; Brown et al., 2006; Charnsil & Bathia, 2010; De Sousa, 2010; Merkaj et al., 2013). However, the reports fluctuate between family members as mothers report more mental health challenges than fathers, including stress, anxiety, and depression (Dabrowska & Pstiula, 2010; Hodapp et al., 2003; Merkaj et al., 2013). Yet, these findings are based on the limited research that has been done on fathers and couples (Cheuk & Lashewicz, 2015; Osborne & Reed, 2008; Papageorgiou & …

Metabolic And Barrier Function In Response To Β-Caryophyllene In Intestinal Epithelial Cells, Hannah Scroggins

Theses and Dissertations--Animal and Food Sciences

Butyrate, a short-chain fatty acid, regulates cellular metabolism and energy status in intestinal epithelial cells. β-caryophyllene (BCP) is a plant-derived compound that may provide advantageous effects on intestinal barrier function and nutrient utilization. The goal of this thesis was to investigate the effects of BCP on butyrate utilization and metabolism in intestinal epithelial cells. Throughout this thesis, Caco-2 cells in hanging inserts in multi-well plates were used as a model for the intestinal barrier. One study was conducted to investigate the effect of BCP on butyrate utilization and barrier function in intestinal epithelial cells. A second study aimed to elucidate …

Integrating Deconstruction And Historic Preservation: A Best Practices Policy Comparison, Kelsey M. Baldwin

MPA/MPP/MPFM Capstone Projects

Carl Elefante, the former president of the American Institute of Architects, famously said, “The greenest building is…one that is already built” (Elefante, 2012). Elefante articulated the environmental benefits of reuse and the significant energy costs associated with demolition and new construction. In 2022, the commercial and residential building sectors produced 31% of the United States’ greenhouse gas (GHG) emissions (EPA, 2025). A large percentage of this is tied to the production of building materials.

Improvement Of Cellular Pattern Organization And Clarity Through Centrifugal Force, Lauren E. Mehanna, James D. Boyd, Shelley Remus-Williams, Nicole M. Racca, Dawson P. Spraggins, Martha E. Grady, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

Rapid and strategic cell placement is necessary for high throughput tissue fabrication. Current adhesive cell patterning systems rely on fluidic shear flow to remove cells outside of the patterned regions, but limitations in washing complexity and uniformity prevent adhesive patterns from being widely applied. Centrifugation is commonly used to study the adhesive strength of cells to various substrates; however, the approach has not been applied to selective cell adhesion systems to create highly organized cell patterns. This study shows centrifugation as a promising method to wash cellular patterns after selective binding of cells to the surface has taken place. After …

Integrating Protein Language Model And Molecular Dynamics Simulations To Discover Antibiofouling Peptides, Ibrahim A. Imam, Shea Bailey, Duolin Wang, Shuai Zeng, Dong Xu, Qing Shao

Chemical and Materials Engineering Faculty Publications

Antibiofouling peptide materials prevent the nonspecific adsorption of proteins on devices, enabling them to perform their designed functions as desired in complex biological environments. Due to their importance, research on antibiofouling peptide materials has been one of the central subjects of interfacial engineering. However, only a few antibiofouling peptide sequences have been developed. This narrow scope of antibiofouling peptide materials limits their capacity to adapt to the broad spectrum of application scenarios. To address this issue, we searched for antibiofouling peptides in the vast sequence pool of the microbiome library using a combination of deep learning-based high-throughput search and molecular …

A Dual Process Model Perspective On Associations Between Parent And Offspring Problem Drinking, Karallyn E. Fitisone

Theses and Dissertations--Psychology

Parental problem drinking (PPD) is a well-established risk factor for adolescent alcohol use, yet the complex mechanisms involved remain underexplored. The present study addresses this critical gap by examining how PPD, parent emotion socialization, and emerging adult problem drinking are associated within the framework of the Dual Process Model of Substance Use. Participants were 2,036 undergraduates who completed an online survey assessing PPD, retrospective reports of parental reactions to their negative emotions in childhood, and students’ current levels of problem drinking, negative urgency, negative emotional reactivity, and emotion-regulation difficulties. Structural equation modeling was used to clarify the roles of emotion-related …

Feeding- And Light-Cycle Synergistically Regulate Mouse Blood Pressure Daily Rhythm Via Bmal1-Dependent And Independent Mechanisms, Tianfei Hou, Wen Su, Aaron Chacon, An-Hsuan Lin, Zhenheng Guo, Ming C. Gong

Physiology Faculty Publications

Cardiovascular health requires the orchestration of the daily rhythm of blood pressure (BP), which responds to changes in light exposure and dietary patterns. Whether rhythmic light and feeding can modulate daily BP rhythm directly or via modulating intrinsic core clock gene Bmal1 is unknown. Using inducible global Bmal1 knockout mice (iBmal1KO), we explored the impact of rhythmic light, rhythmic feeding, or their combination on various physiological parameters. Daily rhythms of BP, heart rate, and locomotor activity were monitored via radiotelemetry, while food intake patterns were tracked using the BioDAQ system. Respiratory exchange ratio (RER) and energy expenditure (EE) were assessed …

Methylome–Proteome Integration After Late-Life Voluntary Exercise Training Reveals Regulation And Target Information For Improved Skeletal Muscle Health, Toby L Chambers, Andrea Dimet-Wiley, Alexander R Keeble, Amin Haghani, Wen-Juo Lo, Gyumin Kang, Robert Brooke, Steve Horvath, Christopher S Fry, Stanley J Watowich, Yuan Wen, Kevin A Murach

Physiology Faculty Publications

Abstract: Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance–resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22–24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7–10 …

Programmable Scanning Diffuse Speckle Contrast Imaging Of Cerebral Blood Flow, Faezeh Akbari, Xuhui Liu, Fatemeh Hamedi, Mehrana Mohtasebi, Li Chen, Lei Chen, Guoqiang Yu

Physiology Faculty Publications

Significance: Cerebral blood flow (CBF) imaging is crucial for diagnosing cerebrovascular diseases. However, existing large neuroimaging techniques with high cost, low sampling rate, and poor mobility make them unsuitable for continuous and longitudinal CBF monitoring at the bedside. Aim: We aimed to develop a low-cost, portable, programmable scanning diffuse speckle contrast imaging (PS-DSCI) technology for fast, high-density, and depth-sensitive imaging of CBF in rodents. Approach: The PS-DSCI employed a programmable digital micromirror device (DMD) for remote line-shaped laser (785 nm) scanning on tissue surface and synchronized a 2D camera for capturing boundary diffuse laser speckle contrasts. New algorithms were developed …

Alternate Quantification Approaches For Cold-Induced Vasodilation In Human Glabrous Skin, J. A. Stout, D. E. Gerow, P. C. Clegg, K. Metzler-Wilson, T. E. Wilson

Physiology Faculty Publications

Introduction: Cold-induced vasodilation (CIVD) is a counterintuitive focal increase in glabrous skin blood flow during cold exposure with unclear local and neural mechanisms. Methods: We tested 12 (8 men, 4 women) healthy subjects’ laser-Doppler flux (LDF; just proximal to the nailbed) and arterial blood pressure (ABP) on a beat-by-beat basis. The experimental hand was exposed to warm (10 min 35°C) and then cold (30 min 8°C) water immersion and the contralateral control hand experienced 22°C–23°C air throughout. We analyzed beat-by-beat oscillations in LDF and ABP via a fast-Fourier transform (FFT) and transfer function analysis (TFA) of LDF to ABP. Results: …

Gastrocnemius Myofiber Type And Mitochondrial Alterations Associated With Peripheral Artery Disease Severity, Kate Kosmac, Rena Dana Wang, Jada Stewart, Parminder Kaur, Ahmed Ismaeel, Haseeb Ahsan, Lisa Hartnell, Esther E. Dupont-Versteegden, Mary M. Mcdermott, Robert L. Sufit, Luigi Ferrucci, Charlotte A. Peterson

Physiology Faculty Publications

The extent of walking impairment varies among individuals with peripheral artery disease (PAD), which may reflect differences in the adaptability of lower extremity muscles to ischemia-reperfusion injury characteristic of the disease. Analyses of gastrocnemius muscle biopsies from 113 individuals with PAD [mean ankle-brachial index (ABI) = 0.65 ± 0.13, 38 (33.6%) women, 76 (67.2%) Black] showed a wide range of myofiber type distributions (9.6%-82.6% type 1 myofibers). The abundance of oxidative type 1 myofibers negatively correlated with ABI (r = −0.22, P = 0.02), a measure of PAD severity. The abundance of type 1 myofibers also negatively correlated to 2a/x …

Inter-Rater Reliability Of Muscle Ultrasonography Performed By Multidisciplinary Novice Sonographers In The Evaluation Of Critically Ill Patients With Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy, Felipe González-Seguel, Vinh Q. Tran, Chaitanya Anil Pal, Zan T. Shareef, Hayley P. Israel, Arimitsu Horikawa-Strakovsky, Yuan Wen, Benjamin R. Griffin, Javier A. Neyra, J. Pedro Teixeira, Kirby P. Mayer

Physiology Faculty Publications

Early diagnosis of muscle wasting in critically ill patients with acute kidney injury requiring continuous kidney replacement therapy (AKI-CKRT) may improve outcomes via timely rehabilitation and nutrition. Muscle ultrasound (MUS) has recently gained traction for assessing muscle atrophy in the intensive care unit (ICU) but requires training to achieve reproducibility. We evaluated the inter-rater reliability of MUS in patients with AKI-CKRT performed by multidisciplinary raters including nephrologists. Two blinded independent raters used portable ultrasound to acquire images of the rectus femoris (RF). All raters were clinicians routinely caring for patients with CKRT in the ICU and were initially novices in …

Neuro293, Joshua T. Moses, Fahad B. Shah, Nicholas M. Mcvay, Dylan E. Capes, Christopher C. Bosse-Joseph, Jocelyn Salazar, Victoria K. Slone, John E. Eberth, Jonathan Satin, Andrew N. Stewart

Physiology Faculty Publications

Efficient interrogation of neurobiology remains bottlenecked by obtaining mature neurons. Immortalized cell lines still require lengthy differentiation periods to obtain neuron-like cells, which may not efficiently differentiate and are challenging to transfect with plasmids relative to other cell lines such as HEK-293's. To overcome challenges with limited access to cells that express mature neuronal proteins, we knocked out the RE1-silencing transcription factor (REST) from HEK-293's to create a novel neuron-like cell, which we name Neuro293. RNA-sequencing and bioinformatics analyses revealed a significant upregulation of genes associated with neurobiology and membrane excitability including pre-/post-synaptic proteins, voltage gated ion channels, neuron-cytoskeleton, as …

S6k1 Is A Targetable Vulnerability In Tumors Exhibiting Plasticity And Therapy Resistance, Saptadwipa Ganguly, Ravshan Burikhanov, Vitaliy M. Sviripa, Sally Ellingson, Jieyun Jiang, Christian M. Gosser, David Orren, Eva M. Goellner, Gautham G. Shenoy, Mahadev Rao, John D’Orazio, Christine F. Brainson, Chang Guo Zhan, Peter H. Spielmann, David S. Watt, Vivek M. Rangnekar

Physiology Faculty Publications

Background: Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. Methods: We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug. The cancer subtype target range of the leading drug was determined by PRISM analysis of over 900 cancer cell lines at the Broad Institute, MA. RNA-sequencing …

Skeletal Muscle Stem Cell Mitochondria Are Transferred To Muscle Fibers In Response To A Hypertrophic Stimulus, Jensen Goh, Julia G. Williams, Sarah E. Ogle, Jai K. Joshi, Logan N. Scott, Benjamin Burke, Alex R. Keeble, Nicholas T. Thomas, Christopher S. Fry, Ahmed Ismaeel, John J. Mccarthy

Physiology Faculty Publications

The fusion of skeletal muscle stem cell (MuSC) to myofibers during hypertrophy has exclusively focused on the transfer of the MuSC nucleus, leaving the fate of other MuSC organelles, such as mitochondria, largely unexplored. The objective of this study was to determine whether MuSCs transfer their mitochondria upon myofiber fusion in response to a hypertrophic stimulus. To achieve this goal, we specifically labeled MuSC mitochondria with Dendra2 fluorescence by crossing the MuSC-specific CreER (Pax7^CreER/CreER) mouse with the Rosa26-Dendra2 mouse to generate the Pax7-Dendra2 mouse. To induce the fusion of MuSC to myofibers, Pax7-Dendra2 mice underwent synergist ablation surgery …