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- Doctor of Philosophy (PhD) Heersink School of Medicine (57)
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Articles 1 - 30 of 58
Full-Text Articles in Medicine and Health Sciences
The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta
The Role Of Histone Methylation In The Medial Temporal Lobe During Long-Term Memory Formation, Swati Gupta
All ETDs from UAB
Several studies have established the importance of epigenetic regulation of gene transcription in the brain during memory consolidation. Epigenetic mechanisms involve modifying the DNA or the associated histone proteins to determine the transcriptional outcome of a gene. The work encompassed in this dissertation serves as an initial investigation for the role of histone lysine methylation mechanisms in regulating gene activation and suppression in the medial temporal lobe that includes entorhinal cortex (EC), hippocampus, and amygdala during memory consolidation. To this end, we found that di-methylation of histone H3 at lysine 9 (H3K9me2) which promotes gene suppression was specific to associative …
Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon
Modulation Of Autoimmune Diabetes By B Cells Specific For N-Acetyl-D-Glucosamine, Brian L. Dizon
All ETDs from UAB
Type I diabetes (T1D) is an autoimmune disease in which ß cells are destroyed by the immune system; however, role of infections in type I diabetes (T1D) pathogenesis is unclear. Reports suggesting that childhood Group A Streptococcal (GAS) infections protected against T1D prompted us to study how antibodies to N-acetyl-D-glucosamine (GlcNAc), which are induced by GAS infection, influenced T1D development. We found that GlcNAc-specific antibodies reacted with ß cell secretory granules, and neonatal NOD mice immunized with GAS or given GAS-immune sera were protected from spontaneous diabetes. Monoclonal GlcNAc-specific IgM blocked activation and effector responses to islet antigens by diabetogenic …
Suppression Of A Nonsense Mutation In A Mouse Model Of Hurler Syndrome, Dan Wang
Suppression Of A Nonsense Mutation In A Mouse Model Of Hurler Syndrome, Dan Wang
All ETDs from UAB
Nonsense suppression therapy utilizes compounds that suppress translation termination at disease-causing premature termination codons (PTCs) to restore full-length, functional protein synthesis. This approach may provide a treatment for many diseases caused by nonsense mutations including Hurler syndrome (mucopolysaccharidosis type I - Hurler, MPS I-H). MPS I-H is a lysosomal storage disease caused by severe &alpha-L-iduronidase deficiency and subsequent lysosomal glycosaminoglycan (GAG) accumulation. In this work, we investigated the effectiveness of nonsense suppression therapy as a treatment for MPS I-H. We first generated a targeted knock-in mouse model that carries the Idua-W392X nonsense mutation homologous to the human IDUA-W402X mutation frequently …
Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells
Siderophore-Mediated Iron Acquisition In Mycobacterium Tuberculosis, Ryan Wells
All ETDs from UAB
Mycobacterium tuberculosis is a dangerous human pathogen that has the capacity to adapt to and survive within the harsh phagosomal environment of macrophages. One obstacle that must be overcome by pathogens is to acquire iron, an essential component and cofactor of proteins required for vital cellular processes. M. tuberculosis meets its iron demands in the face of an array of sequestration strategies of the host by synthesizing and secreting two siderophores called mycobactin and carboxymycobactin. Siderophores are low molecular weight high affinity iron binding compounds that steal iron away from host stores and have been shown to be important for …
Effects Of Stress On Growth Hormone Receptor Signaling, Ryan Marshall Corrick
Effects Of Stress On Growth Hormone Receptor Signaling, Ryan Marshall Corrick
All ETDs from UAB
Growth hormone (GH) regulates body composition via stimulation of protein synthesis and catabolism of adipose tissue, generally promoting maintenance of lean body mass. Following severe injury, GH resistance contributes to muscle protein wasting, adversely impacting morbidity and mortality. In this dissertation research, we sought to determine the mechanisms of GH resistance following injury. To accomplish this, we evaluated GH signaling in a mouse model of severe injury. In the first section of this thesis, we demonstrate severe impairments in hepatic GH signaling occurring in association with an apparent, hemorrhage-dependent cleavage of the GH receptor (GHR). In the second section, we …
Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva
Finding A Cure For Venezuelan Equine Encephalitis Virus (Veev) Infection: The Search For The Antiviral Genes And Vaccine Development., Svetlana Atasheva
All ETDs from UAB
Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus that causes a severe and often fatal disease in equids and humans. To date, despite a continuous public health threat, no vaccines or antiviral drugs against VEEV infection have been developed for human use. In this study we took advantage of accumulated knowledge of capsid protein function in viral replication, assembly and virus-host interactions. Besides being an integral part of the virion, capsid protein is the major determinant of VEEV pathogenesis. This protein is cytotoxic and induces cellular transcriptional shutoff as a countermeasure to the cellular antiviral response. We introduced targeted …
Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson
Innate Immune Mechanisms Against The Atypical Fungal Pathogen Pneumocystis Murina, Michael Paul Nelson
All ETDs from UAB
Pneumonia caused by the fungal pathogen Pneumocystis continues to be the leading cause of morbidity and mortality in AIDS patients. In addition, there are a number of other non-HIV-associated diseases that render an individual susceptible to Pneumocystis infection, including chronic obstructive pulmonary disease. Innate immune mechanisms are important for controlling Pneumocystis lung infection. As alveolar macrophages serve the front lines of lung host defense, our goal was to elucidate their responses during lung Pneumocystis infection. Here, we established a role for Src family kinases in the lung immune response to Pneumocystis, which uncovered a role for alternatively activated alveolar macrophages. …
Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily
Targeting Mitochondrial Function In Diabetic Nephropathy, Colin Reily
All ETDs from UAB
TARGETING MITOCHONDRIAL FUNCTION IN DIABETIC NEPHROPATHY The incidence of diabetes has increased to epidemic proportions over the last 50 years, due to a complex interaction of lifestyle and dietary factors. Changes in physical activity, caloric intake, and the composition of foods consumed over the last century are thought to interact with metabolic syndrome prone subpopulations leading ultimately to diabetes. It is widely accepted that chronic hyperglycemia in the blood characterizes the diabetic condition. Since the discovery of insulin therapy in the first half of the 20th century, diabetics have extended their lifespan considerably, but at the cost of increased morbitity …
The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall
The Role Of St6gal-I Sialylation In Fas (Cd95) Death Receptor Function And Tumorigenesis, Amanda F. Swindall
All ETDs from UAB
The golgi glycosyltransferase, ST6Gal-I, adds a negatively-charged sialic acid in an alpha-2-6 linkage to N-linked glycans. ST6Gal-I is upregulated in many cancers, and is associated with increased metastasis and poor patient prognosis. ST6Gal-I expression has been shown to be driven by oncogenic-ras signaling. However, mechanistic details of the role ST6Gal-I plays in tumor initiation and progression are not well defined. Historically, studies have focused on contributions of ST6Gal-I to the malignant cell phenotypes of migration and invasion. Emerging evidence including studies contained in this dissertation have begun to elucidate a role for ST6Gal-I as a regulator of apoptotic signaling by …
Mycobacterial Iron Acquisition Systems, Christopher M. Jones
Mycobacterial Iron Acquisition Systems, Christopher M. Jones
All ETDs from UAB
Iron is an essential nutrient for the vast majority of organisms; yet, the availability of iron is limited to microorganisms due to the insolubility of ferric hydroxides and to pathogens by iron withholding strategies of their hosts. Many bacteria produce small, high-affinity iron chelators called siderophores to scavenge iron from the environment. In addition, many bacterial pathogens have evolved mechanisms to steal host iron contained in heme, hemoglobin, or transferrin. Mycobacteria are unique genera of bacteria represented by the notorious pathogens Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis (TB) and leprosy, respectively. Tuberculosis remains a global health …
Using Mouse Models To Investigate Ciliopathies, Raymond Carl Pasek
Using Mouse Models To Investigate Ciliopathies, Raymond Carl Pasek
All ETDs from UAB
Cilia and flagella are microtubule based organelles found on nearly every cell type in the mammalian body. Flagella have an essential role in sperm locomotion and reproduction, while motile cilia have a known role in fluid movement in the brain, lungs, and portions of the female reproductive tract. While the role of most primary cilia remained unknown for decades, they are now recognized as being essential to mammalian development, renal homeostasis, and satiety, just to name a few. Because of their widespread presence and importance, dysfunction of cilia and flagella can lead to a variety of human diseases, collectively referred …
Regulation Of P27kip1 By Trip6 And Its Implications In Cancer Progression, Victor T G Lin
Regulation Of P27kip1 By Trip6 And Its Implications In Cancer Progression, Victor T G Lin
All ETDs from UAB
TRIP6 is a focal adhesion molecule that functions as an adaptor protein to mediate diverse cellular functions, including motility and antiapoptotic signaling, through a wide variety of protein-protein interactions. We were able to characterize a novel interaction between TRIP6 and p27KIP1, a CDK inhibitor which can both suppress and promote tumorigenesis, depending on its regulation. TRIP6 expression specifically promotes the AKT-mediated phosphorylation of p27KIP1 at T157, which leads to its cytosolic retention, and accelerates the protein turnover rate of p27KIP1. We also found that phosphorylation of T157 by itself promotes cell motility and can be linked to the formation of …
A Role Of Angiogenin In Models Of Parkinson's Disease, Trent Steidinger
A Role Of Angiogenin In Models Of Parkinson's Disease, Trent Steidinger
All ETDs from UAB
Parkinson's Disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Gene multiplication of alpha-synuclein causes an autosomal dominant inheritance pattern of PD. A mouse model overexpressing alpha-synuclein demonstrates some of the phenotype seen in PD. In a microarray of these mice, a downregulation of angiogenin was observed prior to symptom onset, demonstrating a potential link of angiogenin to pathology in this model. Angiogenin has also been associated with the onset of Amyotrophic Lateral Sclerosis (ALS), and is neuroprotective in models of ALS through activation of the Akt …
Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai
Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai
All ETDs from UAB
Glutamate mediates excitatory synaptic transmission in the central nervous system (CNS). Regulation of glutamate release and uptake shapes the spatiotemporal dynamics of glutamate at and around synapses to influence information transfer between neural cells. This dissertation focuses on the modulation of glutamate release and uptake at excitatory synapses of cerebellar Purkinje cells (PC). In the first project we show that differential expression of PC glutamate transporters controls the amount of glutamate entering the extrasynaptic space, thereby influencing the excitatory responses in surrounding Bergmann glia. This work provides the first evidence that neuronal glutamate uptake affects glial glutamatergic signaling. In the …
The Role Of C-Reactive Protein In Arthritic Disease, Nicholas Ryan Jones
The Role Of C-Reactive Protein In Arthritic Disease, Nicholas Ryan Jones
All ETDs from UAB
C-reactive protein (CRP) is an acute phase protein that is commonly used to evaluate systemic inflammation level. Blood CRP level also correlates very well with rheumatoid arthritis (RA) disease severity. However, CRP has many biological actions that lead one to suspect that it may be playing a role in the development or pathology of the disease. We have directly addressed whether this is the case by the use of novel mouse models (CRP deficiency or transgenic overexpression). We have shown that CRP positively affects collagen-induced arthritis development and progression. In order to thoroughly address the question, we have also reported …
Retinoids And Abnormal Alveolar Development, Masheika L. James
Retinoids And Abnormal Alveolar Development, Masheika L. James
All ETDs from UAB
Extremely preterm infants are at high risk for a form of chronic lung disease called bronchopulmonary dysplasia (BPD), which is characterized by impaired alveolar development. Exposure to hyperoxia and deficiency of vitamin A (VA) contribute to the development of BPD in preterm infants. Randomized controlled trials indicate VA supplementation decreases BPD and/or death. However, 25% of preterm infants continue to remain VA deficient despite supplementation, probably due to impairment in VA transport, VA is stored in the liver as retinyl esters which are transported to the lung and irreversibly metabolized into all-trans-retinoic acid (ATRA), the active metabolite. A combination of …
Antiphagocytic Factors Of Mycoplasma Pulmonis, Brandon Michael Shaw
Antiphagocytic Factors Of Mycoplasma Pulmonis, Brandon Michael Shaw
All ETDs from UAB
Mycoplasma pulmonis is a murine respiratory pathogen and is used as a model for studying chronic mycoplasmal respiratory disease. This organism has been used by many in vivo and in vitro studies to gain a better understanding of host-pathogen interactions in chronic respiratory infection. Studies have shown that alveolar macrophages play an important role in the removal of this pathogen from the host. Given that M. pulmonis is able to produce a chronic disease state, this organism should produce antiphagocytic factors that aid in avoidance of killing by alveolar macrophages. The Vsa proteins are involved in the avoidance of killing …
Analysis Of Ergothioneine Production In Mycobacterium Tuberculosis, Loni Ann Guidry
Analysis Of Ergothioneine Production In Mycobacterium Tuberculosis, Loni Ann Guidry
All ETDs from UAB
Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, currently infects more than two billion people worldwide. Mtb is a highly adaptable pathogen, capable of modifying its metabolism in response to its environment. We previously showed that Mtb WhiB3 is a redox-responsive regulator of core intermediary metabolism and lipid anabolism through which it maintains redox homeostasis. In this work, through the use of metabolomic analysis and a novel radioactive thin layer chromatography assay, we discovered that WhiB3 regulates the production of the intracellular thiol ergothioneine (ergo) when using immunomodulatory lipid precursors as the major carbon source. Our results suggest that this …
Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin
Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin
All ETDs from UAB
Dynamic changes to the actin cytoskeleton are required for synaptic plasticity and long-term memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during both activity-dependent synaptic potentiation and long-term memory encoding are poorly understood. Myosin II motor proteins are highly expressed in actin-rich growth structures in neurons, including dendritic spines. Recent work demonstrates that these molecular machines mobilize F-actin in response to synaptic stimulation and are required for memory encoding in CA1 hippocampus of rodents. The aims of this project were two-fold. First, we sought to establish if myosin II regulates actin filament polymerization necessary for structural …
Modulation Of Wzy-Dependent Capsule Production In Streptococcus Pneumoniae By The Phosphotyrosine-Specific Phosphatase Cpsb, Kimball Aaron Geno
Modulation Of Wzy-Dependent Capsule Production In Streptococcus Pneumoniae By The Phosphotyrosine-Specific Phosphatase Cpsb, Kimball Aaron Geno
All ETDs from UAB
Biosynthesis of capsule polysaccharide in the Gram-positive pathogen Streptococcus pneumoniae is regulated in part through the action of a phosphoregulatory system comprised of the products of the capsule biosynthetic operon genes cpsBCD. CpsC and CpsD together comprise an autophosphorylating tyrosine kinase whose homologs are implicated in chain length regulation in other systems in both Gram-positive and Gram-negative organisms. CpsB is the cognate phosphatase for the system. Unlike Gram-negative organisms, which use a low molecular weight phosphotyrosine phosphatase in phosphoregulation of capsule synthesis, Gram-positive organisms utilize a polymerase and histidinol phosphatase (PHP) superfamily phosphatase. Deletion of cpsB has resulted in conflicting …
Modulation Of Alpha-Synuclein Metabolism And Toxicity By Cathepsin D, Donna Marlana Crabtree
Modulation Of Alpha-Synuclein Metabolism And Toxicity By Cathepsin D, Donna Marlana Crabtree
All ETDs from UAB
Parkinson's disease (PD) is the most commonly occurring neurodegenerative movement disorder, and aberrant accumulation of the protein α-synuclein is thought to be a major contributing factor in disease development. Dysfunction of the autophagy lysosome pathway (ALP) has been implicated in PD pathogenesis. Our lab and others have shown that the lysosomal enzyme cathepsin D (CD) is an important regulator of α-synuclein degradation. The primary focus of this thesis is probing the structure/function dynamic that exists between α-synuclein and CD. We have found that lentiviral-mediated over expression of wild type CD (wtCD) leads to subtle alterations in the ALP in a …
Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis
Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis
All ETDs from UAB
Parkinson disease (PD) is a devastating movement disorder affecting between 500,000 and 1,000,000 individuals in the United States alone, and for which there is currently no cure. Therapies such as dopamine replacement help initially, but with disease progression these lose efficacy and do not alter the underlying degenerative process. Gene therapy is the delivery of exogenous genetic material to correct an underlying disorder. A major advantage of this approach is the ability to distribute potent therapies to specific targets over an extended duration, properties necessary for the treatment of progressive degenerative diseases such as PD. A number of clinical trials …
Mechanisms Of Lrrk2 Regulation, Philip J. Webber
Mechanisms Of Lrrk2 Regulation, Philip J. Webber
All ETDs from UAB
Non-synonymous mutations in LRRK2 are the most common known cause of familial and sporadic Parkinson's disease (PD). The dominant inheritance of these mutations in familial PD suggests a gain-of-function mechanism. Increased kinase activity observed in the most common PD associated LRRK2 mutation G2019S suggests that kinase activity is central to disease. However, not all mutations associated with disease are reported to alter kinase activity and controversy exists in the literature about the effects of mutations appearing in the GTPase domain on kinase activity. The studies conducted as a part of this work aim to characterize the mechanisms that regulate LRRK2 …
Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu
Fcrl5 Exerts Binary And Compartment-Specific Influence On Innate-Like B Cell Receptor Signaling, Zilu Zhu
All ETDs from UAB
Innate-like splenic marginal zone (MZ) and peritoneal cavity (PEC)-derived B1 B lymphocytes are the major contributors to primary humoral responses and play an important role in connecting innate and adaptive immunity, but are known to significantly differ in their B cell receptor (BCR) signaling characteristics. In mice, FCRL5 is discretely expressed by innate-like MZ and B1 B cells and is furthermore equipped with cytoplasmic ITAM-like and ITIM elements, suggesting diverse signaling potential for it. Our results showed that FCRL5 markedly inhibited BCR-mediated activation in MZ B cells, but not in PEC B1 B cells. To characterize its signaling function, a …
Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman
Evaluating The Efficacy Of Radiofrequency Amplitude-Modulated Electromagnetic Fields As A Novel Treatment For Hepatocellular Carcinoma, Jacquelyn Winifred Zimmerman
All ETDs from UAB
Hepatocellular carcinoma (HCC) incidence in the US is dramatically increasing. Five-year survival has remained 3-5% for the past several decades, demonstrating urgent need for additional therapies. Intrabuccal administration of amplitude-modulated radiofrequency electromagnetic fields (RF EMF) is a novel, minimally invasive treatment modality. Clinical evidence demonstrates this treatment approach elicits therapeutic responses in cancer patients. In vitro we have described a phenotype in HCC cells following RF EMF exposure that included proliferative inhibition, modulation of gene expression, and disruption of the mitotic spindle. This phenotype was specific for HCC cells exposed to HCC-specific RF EMF. We have demonstrated similar efficacy in …
Regulatory T Cells In The Fvb.Mdr1a-/- Model Of Colitis, Scott Tanner
Regulatory T Cells In The Fvb.Mdr1a-/- Model Of Colitis, Scott Tanner
All ETDs from UAB
Regulatory T cells (Treg) are necessary for the maintenance of immune homeostasis, and have been implicated in several autoimmune diseases, including inflammatory bowel disease (IBD). Most murine studies focusing on the function of Tregs have been done on the C57BL/6 or BALB/c background, creating a bias towards these two strains. In addition, it has been shown that C57BL/6 and BALB/c Tregs function in different manners. To further investigate potential strain differences in Treg phenotype and function, we chose to analyze FVB/N Tregs. Several differences were observed, including de-creased FVB/N Treg suppression in a non-cell contact dependent manner, decreased FVB/N and …
Modulation Of Capsule Production In Serotype 3 Streptococcus Pneumoniae, Melissa Ellis
Modulation Of Capsule Production In Serotype 3 Streptococcus Pneumoniae, Melissa Ellis
All ETDs from UAB
Streptococcus pneumoniae is a Gram-positive pathogen and an important cause of community-acquired pneumonia and meningitis, and it can also cause otitis media and bacteremia. A major virulence factor of S. pneumoniae is its polysaccharide capsule which functions to prevent complement-mediated opsonophagocytosis. At least 93 distinct serotypes that vary in sugar composition and structure exist. S. pneumoniae can asymptomatically colonize the nasopharynx and transition to other body sites such as the lungs and blood causing invasive disease. The ability to regulate capsule production in these vastly different environments is critical for survival as low levels of capsule are necessary for colonization, …
Functional Collaboration Between Igf-1 Receptor And Growth Hormone Signaling Pathway, Yujun Gan
Functional Collaboration Between Igf-1 Receptor And Growth Hormone Signaling Pathway, Yujun Gan
All ETDs from UAB
GH receptor (GHR) binds GH in its extracellular domain (ECD) to activate the GHR-associated cytoplasmic tyrosine kinase, JAK2. IGF-1 binds IGF-1R, a disulfide-linked heterotetramer with tyrosine kinase activity in its intracellular domain (ICD). Classically, IGF-1 is a GH effector in a “linear” GH→GHR→IGF-1→IGF-1R pathway. Our recent studies suggest IGF-1R also subserves GH signaling in several novel ways: 1) GH induces a GHR-JAK2-IGF-1R complex, whose formation is independent of tyrosine phosphorylation of any of the partners; 2) Cotreatment with IGF-1 augments acute GH signaling; 3) deletion of IGF-1R in primary osteoblasts or human prostate cancer cells blunts acute GH signaling. In …
Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh
Regulation Of Neuronal Cell Death By Bh3-Only Proteins, Arindam P. Ghosh
All ETDs from UAB
Apoptosis in metazoan organisms plays critical roles in normal development, tissue homeostasis and immunity, and its disturbed regulation leads to many pathological states, including cancer, autoimmunity, infection and degenerative disorders. Apoptosis can be triggered by the engagement of `death receptors' of the tumor necrosis factor receptor family on the cell surface or by diverse intracellular signals that act upon the BCL2 (B-cell CLL/lymphoma 2) protein family, which controls the integrity of the mitochondrial outer membrane through the complex interactions of family members. Both the pathways lead to cellular demolition by dedicated proteases termed caspases. Different BH3-only proteins (or combinations of …
Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps
Development Of Electrospun Bone-Mimetic Matrices For Bone Regenerative Applications, Matthew Christopher Phipps
All ETDs from UAB
Although bone has a dramatic capacity for regeneration, certain injuries and procedures present defects that are unable to heal properly, requiring surgical intervention to induce and support osteoregeneration. Our research group has hypothesized that the development of a biodegradable material that mimics the natural composition and architecture of bone extracellular matrix has the potential to provide therapeutic benefit to these patients. Utilizing a process known as electrospinning, our lab has developed a bone-mimetic matrix (BMM) consisting of composite nanofibers of the mechanically sta-ble polymer polycaprolactone (PCL), and the natural bone matrix molecules type-I colla-gen and hydroxyapatite nanocrystals (HA). We herein …