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Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell Jan 2016

Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell

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It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …

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Development Of An In Vitro, Three-Dimensional Microvasculature Model, Lauren Elizabeth Marshall Jan 2016

Development Of An In Vitro, Three-Dimensional Microvasculature Model, Lauren Elizabeth Marshall

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Vascularized in vitro models of breast cancer represent an important advance in preclinical drug testing and development. 3D in vitro tissue models are more physiologically-relevant than 2D cell culture models due to the combination of human cells and extracellular matrix (ECM) in a spatial 3D microarchitecture. Embedding a vasculature within a 3D tissue volume further increases its physiological relevance and enables paracrine cross-talk with other cell types, neovascularization and angiogenesis, size-selective permeability between blood flow and extravascular ECM, delivery of therapeutics and metabolized products to solid tumors, delivery of circulating tumor cells to metastatic sites, and production of growth-promoting and …

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Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy Jan 2016

Neurodevelopmental Alterations In A Rodent Model Of Temperamental Differences, Chelsea Mccoy Mccoy

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Understanding biological mechanisms that shape brain development and susceptibility to emotional dysfunction is crucial for generating improved treatments for depression and anxiety disorders. To study neurodevelopmental factors that influence emotionality, we use model rats that were bred for distinct behavioral responses to novelty. Rats bred for low novelty response (LRs) exhibit a high anxiety-/depressive-like phenotype compared to high novelty responder rats (HRs), which vigorously explore novelty and exhibit high impulsivity, aggression, and risk-taking. Transcriptome profiling revealed multiple gene expression differences in the early postnatal hippocampus and amygdala and in the adult amygdala of HR/LR rats. Through gene ontology analysis, we …

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Conjunctival Gene Expression And Tear Biomarkers In Atopic And Non-Atopic Keratoconus Patients Relative To Matching Controls, Erika Marie Morrow Jan 2016

Conjunctival Gene Expression And Tear Biomarkers In Atopic And Non-Atopic Keratoconus Patients Relative To Matching Controls, Erika Marie Morrow

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Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley Jan 2016

Transcriptional Regulation Of Interleukin 10 In Cd4+ T Cells, Carson Edward Moseley

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Autoimmune and autoinflammatory diseases are a collection of disorders that are mediated by reaction of the adaptive immune system against self or commensal antigens. Altered transcription of genes involved in T cell activation and function is a key mediator of predisposition to numerous autoimmune disorders, including Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). However, we have an inadequate understanding of how the transcriptional circuits controlling these genes are dysregulated in disease. Interleukin-10 (IL-10) is cytokine with potent anti-inflammatory activity that is critical for restraining immune-mediated pathology to self-tissues. Notably, patients with nullifying mutations in IL10 develop a severe IBD …

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The Effects Of Six Weeks Of High Intensity Interval Training (Hiit) Or Moderate Intensity Training (Mit) On Antioxidant Capacity And Metabolic Health In Obese/Overweight Males, Samuel Pierce Cauffman Jan 2016

The Effects Of Six Weeks Of High Intensity Interval Training (Hiit) Or Moderate Intensity Training (Mit) On Antioxidant Capacity And Metabolic Health In Obese/Overweight Males, Samuel Pierce Cauffman

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Background: Obesity is an independent risk factor for type 2 diabetes and cardiovascular disease. Oxidative stress or low total antioxidant capacity has been shown to be associated with decreased insulin sensitivity (SI) in overweight/obese individuals. Exercise training has been shown to improve systemic antioxidant capacity (TAC) and SI; however whether or not correlations between SI and TAC observed under untrained conditions are associated following exercise training is less clear. PURPOSE: The purpose of this study was twofold: 1) to determine if SI was correlated with serum TAC in a cohort of overweight/obese men at baseline and following six-weeks of exercise …

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Cultural Competence Practices Implemented In Hospitals And Health Systems By Minority Executives On The Top Management Team, John H. Cunningham Jan 2016

Cultural Competence Practices Implemented In Hospitals And Health Systems By Minority Executives On The Top Management Team, John H. Cunningham

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The study examined whether hospital implementation of cultural competence practices was influenced by the racial/ethnic composition of top management. With one-third of the U.S. population identifying with a racial or ethnic group other than non-Hispanic White, and that population continuing to grow increasingly diverse, racial and ethnic minorities are increasingly accessing health care services. Yet they represent less than 1% of the top management teams (TMT) of health care organizations. The study sought to determine the extent to which health care organizations with TMTs that are representative of the racial and ethnic compositions of the communities in which they serve …

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Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs Jan 2016

Human Cytosolic Sulfotransferase (Sult) 1b1 Half-Site Reactivity And The Identification And Characterization Of A Novel Variant Sult1b1 Isoform (L145v), Zachary Evan Tibbs

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The human cytosolic sulfotransferases (hSULTs) are a fourteen-member family of phase II drug-metabolizing enzymes that catalyze the transfer of a sulfonate moiety from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to a recipient substrate. SULT-mediated sulfation serves to deactivate physiological hormones and detoxify xenobiotics. SULT1B1 is primarily resident to the gastrointestinal tract, liver, and possibly peripheral white blood cells (WBCs), whereby it performs its supposed physiological role. The iso-form has the capacity to sulfate thyroid hormones, small phenols, and polyaromatic hy-drocarbons resulting in their inactivation, detoxification, and bioactivation/detoxification, respectively. Immunohistochemistry was used to show hSULT1B1 protein is present in periph-eral lymphocytes and neutrophils. Further, …

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Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome Jan 2016

Microglia Orchestrate The Inflammatory Response To Alpha-Synuclein In Parkinson Disease Models, Aaron Thome

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Parkinson disease (PD) is the most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein alpha-synuclein (α-syn). Increasing evidence points to inflammation as a chief mediator of PD with many of the inflammatory manifestations of human PD cases recapitulated in animal models of PD. We began by examining the inflammatory potential of α-syn fibrils, a newly characterized α-syn conformation that is neurotoxic and prion-like in its endogenous α-syn recruitment and cellular transmission. Our studies provide evidence that the α-syn fibrils evoke a pro-inflammatory response …

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Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien Jan 2016

Polycomb Repressive Complex 2 And Heterochromatin Protein 1 Beta Regulate Neural And Neural Crest Development, Chih-Liang Tien

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Epigenetic factors control gene expression via modulating chromatin conformation. Current studies on epigenetics mainly focus on biochemical mechanisms or functions of epigenetic factors in cancer or neurobiology. The underlying mechanism for epigenetic regulation in early embryonic development, particularly neural and neural crest development, is not well understood. In this thesis, the model organism, Xenopus laevis, is used to study epigenetic factors – polycomb repressive complex 2 (PRC2) and heterochromatin protein 1 beta (HP1β) in neural and neural crest development. In chapter one, the processes of neural and neural crest development are described, and the concepts of epigenetic mechanisms, such as …

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Methods For Analysis Of Genetic Differences In Sex And Ethnicity For Complex Human Traits, Yogasudha Veturi Veturi Jan 2016

Methods For Analysis Of Genetic Differences In Sex And Ethnicity For Complex Human Traits, Yogasudha Veturi Veturi

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In the last two decades, thousands of genome-wide association (GWA) analyses have been published. These studies have been primarily conducted using data from Caucasians and many of the reported findings have not been replicated in other populations, perhaps reflecting that the underlying architecture of effects may vary across ethnically diverse groups. Similarly, the possibility that the genetic architecture of traits may vary between males and females has also been overlooked. We propose a methodology for estimation and testing of effect heterogeneity between groups such as sex or ethnicity that involves modeling genotype-by-group random interactions. Using simulations, we show that the …

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Germline Restriction Of B Cell Receptor Repertoire Influences Antigenic Epitope Recognition And Primary Antibody Deficiency Pathogenesis, Yuge Wang Jan 2016

Germline Restriction Of B Cell Receptor Repertoire Influences Antigenic Epitope Recognition And Primary Antibody Deficiency Pathogenesis, Yuge Wang

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Part I. Mouse Studies Complementarity determining region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while …

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Cell Signaling Pathways As Targets For Precision Medicine In Head And Neck Squamous Cell Carcinoma, Alice Weaver Jan 2016

Cell Signaling Pathways As Targets For Precision Medicine In Head And Neck Squamous Cell Carcinoma, Alice Weaver

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high rates of recurrence and mortality. Unlike other cancer types, genome sequencing studies have failed to produce clinically actionable targets to improve HNSCC management. Therefore, alternative methods are needed to study the molecular mechanisms responsible for disease progression and response to therapy. The focus of this research was to determine how dysregulation of cell signaling pathways affects outcomes in HNSCC. In HPV-positive HNSCCs, we hypothesized that HPV induces dysregulation of the DNA damage response which mediates differences in therapeutic sensitivity and survival. We identified a defect in DNA …

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Paper Me, Matthew David Whitehurst Jan 2016

Paper Me, Matthew David Whitehurst

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Paper Me is an autobiographical collage. It contains memoir essays, personal essays and comedic essays. Dark humor and sarcasm are the vehicle for the narrative voice throughout the collage. The narrative is arranged in a pseudo-chronological order, and traces a line through dotted memories: from the first memory as a child in pre-school, to the death of a friend after college. Addiction, Paternal Relationships, Politics, Absurdity/Humor, Poverty, Sociology and Philosophy are recurring themes in this collection. This is the author’s attempt to concretize a world view, as informed by personal experience, and to impart that experiential knowledge on the larger …

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Temporal Co-Expression Network Construction, Leading Sub-Network Identification, And Time Point Alignment In The Integration Of Phase Transition Theory And Systems Biology And The Application To Human Type 1 Diabetes, Nathaniel Wolanyk Jan 2016

Temporal Co-Expression Network Construction, Leading Sub-Network Identification, And Time Point Alignment In The Integration Of Phase Transition Theory And Systems Biology And The Application To Human Type 1 Diabetes, Nathaniel Wolanyk

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Systems biology is a rapidly expanding field used to tackle a wide range of biological problems. Systems biology arose to explain areas that detailed biological analysis, such as genetics and biopsies, struggled with. Systems biology is the study of the complexity within a biological system of multiple units that is due to the interaction among the units. In this dissertation systems biology will be combined with phase transition theory from physics to create a new analysis method for complex diseases and apply this new method to a longitudinal dataset on Type 1 Diabetes (T1D) to identify the key contributing molecules …

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Influence Of Maternal Age On The Effects Of Organic Selenium In The Animal Model Daphnia Pulex, Jordan E. Roberts Jan 2016

Influence Of Maternal Age On The Effects Of Organic Selenium In The Animal Model Daphnia Pulex, Jordan E. Roberts

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As a necessary micronutrient, seleno-L-methionine (SeMet) exhibits a U-shaped dose-response with deficiency and toxicity leading to adverse health outcomes. Some studies suggest dietary selenium may offer protection against toxicity from other metals, but excessive dietary levels can also lead to toxicity. In addition, increased maternal age has been shown to increase the risk of adverse developmental outcomes. We hypothesize that older maternal age will increase susceptibility in offspring exposed to toxic concentrations of SeMet. The goal of this project was to evaluate the effects of SeMet treatment on lifespan and determine if the effects are altered by maternal age using …

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Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer Jan 2016

Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer

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Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …

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"Sleep Tight, Don't Let The Dysfunction Bite!" The Relationship Between Sleep Problems And Behavioral And Emotional Problems In Adolescence, Meredith Ashley Henry Jan 2016

"Sleep Tight, Don't Let The Dysfunction Bite!" The Relationship Between Sleep Problems And Behavioral And Emotional Problems In Adolescence, Meredith Ashley Henry

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The effects of sleep on behavioral and emotional functioning in a low income, urban sample of 84 African American adolescents was investigated over 3 years (mean ages: 13.36, 14.76, and 16.14 years) of parent and child interviews. Results suggest child-reported sleep duration decreased while all other sleep variables remained stable. Substance use increased over time. Physical aggression and conduct problems decreased; depression, emotional problems, and hyperactivity/inattention remained stable until late adolescence and then decreased. Lower duration of sleep and more sleep problems at age 13 predicted more conduct problems at age 15 which, in turn, predicted less sleep duration and …

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What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill Jan 2016

What's Up, Dut? Help, Help I'M Being Derepressed; The Great Derepression Of Sapis Or How I Learned To Stop Worrying And Love Mobilization, Rosanne Lorin Lee Hill

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Staphylococcus aureus is known to cause disease in both human and animal populations. Many of the virulence factors important for S. aureus pathogenesis are found on mobile genetic elements known as S. aureus pathogenicity islands (SaPIs). SaPIs can transduce into surrounding cells, giving those cells the ability to produce virulence factors. Derepression allows SaPIs to be excised from S. aureus genome to initiate mobilization. Derepressors have been identified for multiple SaPIs, but it remains unknown if the same SaPI can be derepressed by multiple derepressors. It has been shown that SaPIbov1 can be derepressed by the type 1 dUTPase from …

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The Effects Of Perceived Stress, Sleep, And Stress Response On Cancer Related Fatigue In 8- To 12-Year-Old Central Nervous System Cancer Survivors, Ann Johnson Jan 2016

The Effects Of Perceived Stress, Sleep, And Stress Response On Cancer Related Fatigue In 8- To 12-Year-Old Central Nervous System Cancer Survivors, Ann Johnson

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Survivors of childhood cancer are a growing population, and knowledge of persistent cancer related fatigue (CRF) is integral to survivorship. CRF in central nervous system (CNS) cancer is multifactorial and may be unique based on treatment and stage of survival. There is a gap in evidence for school-age survivors, especially during early survivorship. Aims: The aim of this study was to examine factors that influence CRF in child CNS cancer survivors at least 6 months and less than 6 years post treatment. The purpose of this study was to examine relationships between select factors and CRF and to determine effect …

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Plasma Enhanced Chemical Vapor Deposition Of Metal-Boride Interfacial Layers As Diffusion Barriers For Nanostructured Diamond Growth On Cobalt Containing Alloys Cocrmo And Wc-Co, Jamin Michael Johnston Jan 2016

Plasma Enhanced Chemical Vapor Deposition Of Metal-Boride Interfacial Layers As Diffusion Barriers For Nanostructured Diamond Growth On Cobalt Containing Alloys Cocrmo And Wc-Co, Jamin Michael Johnston

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This work is a compilation of theory, finite element modeling and experimental research related to the use of microwave plasma enhanced chemical vapor deposition (MPECVD) of diborane to create metal-boride surface coatings on CoCrMo and WC-Co, including the subsequent growth of nanostructured diamond (NSD). Motivation for this research stems from the need for wear resistant coatings on industrial materials, which require improved wear resistance and product lifetime to remain competitive and satisfy growing demand. Nanostructured diamond coatings are a promising solution to material wear but cannot be directly applied to cobalt containing substrates due to graphite nucleation. Unfortunately, conventional pre-treatment …

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Resveratrol And Pterostilbene: A Novel Combinatorial Epigenetic Therapy In Targeting Triple-Negative Breast Cancer, Rishabh Kala Jan 2016

Resveratrol And Pterostilbene: A Novel Combinatorial Epigenetic Therapy In Targeting Triple-Negative Breast Cancer, Rishabh Kala

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Although the majority of breast cancers are estrogen receptor (ER)-positive, progesterone receptor (PGR)-positive and/or HER2 positive, approximately 20% of them are triple-negative and lack ER, PGR and HER2 protein expression. These cancers are robust and hard to treat with conventional hormone therapies. The plant-based dietary compounds resveratrol and pterostilbene (a dimethyl derivative of resveratrol) have been shown to modulate the growth of cancer cells individually via affecting genetic and epigenetic profiles, but none of the studies to date have addressed the effects of these two compounds in combination in targeting triple-negative breast cancers (TNBC). We have discovered a synergistic effect …

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Separate But Equal: A Phenomenological Study Of Teachers' Experiences With African American Males In Gender-Specific Classrooms In An Urban School Setting, Hamidah Elmore Jan 2016

Separate But Equal: A Phenomenological Study Of Teachers' Experiences With African American Males In Gender-Specific Classrooms In An Urban School Setting, Hamidah Elmore

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The purpose of this phenomenological study was to illuminate teachers’ experiences with African American males in gender-specific classrooms in an urban school setting in an inner-city school system in Alabama. The central question, “What is it like to be a teacher of African American males within a gender-specific classroom?” guided this qualitative study. This question spawned several sub-questions: (1) “What characteristics are common in an African-American male gender-specific instructor?”, (2) “What strategies do successful African-American male gender specific instructors use in their teaching?”, (3) “What types of administrative support are useful for African-American male gender-specific instructors?”, and (4) “What types …

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Mechanical Properties Of The Growth Plate In A Rat Model Of Obesity, Patrick Neil Estep Jan 2016

Mechanical Properties Of The Growth Plate In A Rat Model Of Obesity, Patrick Neil Estep

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The other group (group 2) of 50 women received the same intervention with heel QUS

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Electrospun Polycaprolactone Scaffolds: Mechanical Properties, Alignment Quantification, And Topology Induced Gene Expression, Timothy John Fee Jan 2016

Electrospun Polycaprolactone Scaffolds: Mechanical Properties, Alignment Quantification, And Topology Induced Gene Expression, Timothy John Fee

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Producing tissue engineering scaffolds which mimic the structure and mechanical properties of the native extracellular matrix (ECM) is an important challenge in developing synthetic tissue replacements. Electrospinning is a frequently used technique to fabricate 3D nanofibrous scaffolds which match the dimensions of the fibrous elements of ECM. However, the mechanical behavior of electrospun materials is complex and challenging to predict. To aid in understanding the mechanical properties of electrospun materials, a microtensile testing platform was developed. This platform was used to quantify the mechanical properties of arrays of individual electrospun nanofibers. Additionally, this device permitted optical strain recording to visualize …

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The Role Of Ppar-Delta In Regulating Cardiomyocyte Proliferation And Angiogenesis In Post-Myocardial Infarction Adult Heart, Yishu Ding Jan 2016

The Role Of Ppar-Delta In Regulating Cardiomyocyte Proliferation And Angiogenesis In Post-Myocardial Infarction Adult Heart, Yishu Ding

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immediately before, soon after, and one month after intervention. Average daily calcium

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Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham Jan 2016

Examination Of 4-Hydroxy Tamoxifen- And Bh3 Mimetic-Induced Cell Death Pathways In Glioblastoma And Malignant Peripheral Nerve Sheath Tumor Cells, Christopher Dillon Graham

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Glioblastoma (GBM) is the most common and aggressive human primary malignant brain tumor with a 5-year survival rate of less than 5%. GBM is highly invasive, rendering complete surgical resection impossible. Additionally, this tumor type is relatively insensitive to radiotherapy. Thus, effective chemotherapeutic options present the last line of defense for GBM patients. Unfortunately, nearly 50% of all GBM tumors are resistant to the current chemotherapeutic standard, temozolomide (TMZ). TMZ is a DNA alkylating agent that promotes apoptosis via DNA damage. Resistance to TMZ-induced cell death is attributed to expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) resultant from …

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Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson Jan 2016

Genome-Wide Transcription And Dna Methylation Profiling In An App Mouse Model Of Alzheimer’S Disease, Mikael C. Guzman Karlsson

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The ability to encode information for long-term behavioral adaptation relies on experience-dependent alterations in neuronal plasticity. Neuronal plasticity encompasses the cellular and molecular changes that modulate synaptic communication between neurons as well as intrinsic electrophysiological properties within neurons. Epigenetic mechanisms, including DNA cytosine methylation and histone post-translational modifications, are powerful regulators of neuronal gene expression, allowing for dynamic, bidirectional regulation of transcriptional signatures necessary for neuronal plasticity. Emerging evidence using candidate-gene and microarray-based approaches suggest that the deficits in neuronal plasticity and cognitive impairment observed in Alzheimer’s disease (AD) is attributable, in part, to aberrant cytosine methylation and transcription of …

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Elucidating The Role Of The Pro-Survival To Pro-Death Molecular Switch In The Ire1a Signaling Pathway In Arabidopsis Thaliana, Marie Vollmer Alexander Jan 2016

Elucidating The Role Of The Pro-Survival To Pro-Death Molecular Switch In The Ire1a Signaling Pathway In Arabidopsis Thaliana, Marie Vollmer Alexander

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In eukaryotic cells, the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) results in ER stress that induces a cascade of reactions termed the unfolded protein response (UPR). The most conserved UPR sensor amongst eukaryotes, Inositol-Requiring Enzyme 1 (IRE1), responds to ER stress by activating a pathway that, under normal conditions, would up-regulate the cellular pro-survival pathway. However, under extreme conditions the infected portion of the plant will ultimately “switch” from pro-survival to pro-death in order to avoid further unfavorable circumstances for the plant as a whole. Arabidopsis possesses two homologs of the major UPR sensor, IRE1a …

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Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser Jan 2016

Novel Biomarkers For Parkinson Disease, Kyle Bradley Fraser

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Parkinson disease (PD) is the most common neurodegenerative movement disorder for which no treatments exist capable of slowing progression of the disease. One obstacle slowing the development of novel therapies is the lack of molecular biomarkers for PD prognosis, tracking of disease progression, and assessing efficacious target engagement of compounds that do reach clinical trials. Missense mutations in LRRK2 account for between 1-5% of late onset PD and lead to increases in LRRK2 kinase activity and LRRK2 autophosphorylation. This thesis characterizes the secretion of LRRK2 into extracellularly secreted microvesicles called exosomes. We find that kinase-active LRRK2 is secreted within exosomes …

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