2,777 Works

Temporal Organization of Behavioral States through Local Neuromodulation in C. elegans

Navonil Banerjee
Neuropeptide signaling play critical roles in maintaining distinct behavioral states and orchestrating transitions between them. However, elucidating the mechanisms underlying neuropeptide modulation of neural circuits in vivo remains a major challenge. The nematode Caenorhabditis elegans serves as an excellent model organism to study neuropeptide signaling mechanisms encoded in relatively simple neural circuits. We have used the C. elegans egg-laying circuit as a model to understand how neuropeptide signaling modifies circuit activity to generate opposing behavioral...

HIV-1 and the Nucleolus: A Role for Nucleophosmin/NPM1 in Viral Replication: A Dissertation

Tracy E. Schmidt

Role of Autophagy in Post-Mitotic Midbody Fate and Function: A Dissertation

Tse-Chun Kuo

Role of Inflammation in Diet-Induced Obesity: A Dissertation

Sophia Kogan

Regulation of Alloreactive CD8 T Cell Responses by Costimulation and Inflammation

Sonal Jangalwe
CD8 T lymphocytes are a crucial component of the adaptive immune system and mediate control of infections and malignancy, but also autoimmunity and allograft rejection. Given their central role in the immune system, CD8 T cell responses are tightly regulated by costimulatory signals and cytokines. Strategies targeting signals that are critical for T cell activation have been employed in a transplantation setting to impede alloreactive T cell responses and prevent graft rejection. The goal of...

A Two-Pronged Approach to Preeclampsia: Understanding Gene Expression and Targeting sFlt1 using RNAi

Ami Ashar-Patel
Preeclampsia (PE) is a disorder affecting 2-10% of pregnancies worldwide. Clinical signs include high blood pressure (HBP) and proteinuria in the mother after the 20th week of pregnancy. Currently, the only cure for PE is delivery of the fetus, which is often necessary preterm and thus dangerous for both mother and fetus. Maternal symptoms of PE are caused by excess anti-angiogenic proteins of placental origin called soluble Flt1s (sFlt1s). sFlt1 mRNA isoforms are produced by...

dSarm/Sarm1 Governs a Conserved Axon Death Program: A Dissertation

Jeannette M. Osterloh

Understanding Neural Networks in Awake Rat by Resting-State Functional MRI: A Dissertation

Zhifeng Liang

Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor

Srinjoy Chakraborti
Neisseria gonorrhoeae (Ng) which causes gonorrhea has become multidrug-resistant, necessitating the development of novel therapeutics and vaccines. mAb 2C7 which targets an epitope within an important virulence factor, the lipooligosaccharide (LOS), is a candidate therapeutic mAb. Ninety-four percent of clinical isolates express the 2C7-epitope which is also a vaccine target. Ng expresses multiple LOS(s) due to phase-variation (pv) of LOS glycosyltransferase (lgt) genes. mAb 2C7 reactivity requires a lactose extension from the LOS core Heptose...

Platelet Transcriptome Heterogeneity: A Role for RNA Uptake in Vascular Health and Disease

Lauren Clancy
As our understanding of the platelet’s systemic role continues to expand beyond hemostasis and thrombosis, interrogation of the platelet’s ability to affect diverse biological processes is required. Studies of the platelet’s non-traditional roles have focused on developing our understanding of the platelet’s relation to specific disease phenotypes as well as elucidation of platelet characteristics, content, and function. The generic content, traditional function and heterogeneity of platelets have long been accepted; more ambiguous and controversial has...

A Systems Approach to Dissecting Immune Gene Regulatory Networks in the Modulation of Brain Function

Yang Xu
Although the central nervous system was long perceived as the ivory tower without immune entities, there is growing evidence that the immune and nervous systems are intimated connected. These two systems have been shown to communicate both cellularly and molecularly under physiological and pathological conditions. Despite our increasing understanding of the interplay between these two systems, there are still numerous open questions. In this thesis, I address such unanswered questions related to: the role of...

Identification of KIT as a Suppressor of BRAFV600E-Mutant Melanoma

James Neiswender
Genetic changes acquired in the pigment producing cells of the skin, called melanocytes, can lead to formation of the deadly cancer melanoma. Mutations or amplifications leading to the activation of the RAS/MAPK pathway occur in more than 90% of melanomas. Melanocyte development and survival requires the stimulation of this pathway by the receptor tyrosine kinase (RTK) KIT. In ~2% of melanomas, oncogenic KIT mutations drive tumor formation; however, the majority of melanomas lose wild-type KIT...

Late Antigen Regulates the Differentiation of Cytotoxic CD4 T Cells in Influenza Infection

Allen Vong
CD4 T cells differentiate into multiple effector subsets that mediate pathogen clearance. ThCTL are anti-viral effectors with MHC-II restricted cytotoxicity. The factors regulating ThCTL generation are unclear, in part due to a lack of a signature marker. I show here that in mice, NKG2C/E identifies ThCTL that develop in the lung during influenza A virus (IAV) infection. ThCTL phenotype indicates they are highly activated effectors with high levels of binding to P-selectin, T-bet, IFNγ production,...

Characterization of Adipose Tissue Inflammation in Alcoholic Liver Disease

Melissa Fulham
Adipose tissue inflammation has an impact on liver health and it has been demonstrated that chronic alcohol consumption leads to the expression of pro-inflammatory markers in the adipose tissue. A thorough characterization of alcohol-induced adipose inflammation is lacking, and is important to understand in order to identify immune-related mechanisms that drive this phenomenon. Current therapeutic regimens for alcoholic liver disease are ineffective. It is critical to understand how other organs influence liver injury in this...

Understanding Multiple Independent Functions of the Tip60 Acetyltransferase in Embryonic Development

Diwash Acharya
Chromatin is a dynamic structure, and chromatin remodeling enzymes regulate chromatin structure to control gene expression and proper lineage specification. Tip60-p400 is a multi-subunit chromatin remodeling complex containing two biochemical activities: the Tip60 subunit is a lysine acetyltransferase (KAT) that targets histones and non-histone proteins, and p400 catalyzes ATP-dependent incorporation of histone variant H2AZ into chromatin. Both of these chromatin modifications have been widely studied with respect to gene expression, DNA damage repair, and apoptosis....

The cJUN NH2-terminal kinase pathway in mammary gland biology and carcinogenesis

Nomeda Girnius
The cJUN NH2-terminal kinase (JNK) pathway responds to environmental stresses and participates in many cellular processes, including cell death, survival, proliferation, migration, and genome maintenance. Importantly, genes that encode components of the JNK signaling pathway are frequently mutated in human breast cancer, but the functional consequence of these mutations in mammary carcinogenesis is unclear. Anoikis – suspension-induced apoptosis – has been implicated in oncogenic transformation and tumor cell metastasis. Anoikis also contributes to lumen formation...

Mechanisms Regulating the Dopamine Transporter and Their Impact on Behavior

Carolyn Sweeney
Dopamine (DA) is central to movement, reward, learning, sleep, and anxiety. The dopamine transporter (DAT) spatially and temporally controls extracellular dopamine levels by taking DA back up into the presynaptic neuron. Multiple lines of evidence from studies using pharmacological DAT blockade or genetic DAT deletion demonstrate that DAT availability at the plasma membrane is required for maintenance of homeostatic DA levels and DA tone. Therefore, intrinsic mechanisms that regulate the transporter’s availability at the plasma...

Opioid Use and Safety in United States Nursing Homes

Jacob Hunnicutt
Background: Opioids are often used in nursing homes to manage non-malignant pain, but little is known about their long-term use, initiation, and comparative safety. Methods: We used the Minimum Data Set 3.0 from 2011-2013 merged to Medicare and facility characteristics data to study opioid use and safety among older, long-stay residents. The specific aims were to examine the 1) prevalence of long-term opioid use; 2) geographic variation in the initiation of commonly used opioids (oxycodone,...

Li Fem Anpil: The Lived Experience of Haitian Immigrant Women with Postpartum Depression

Colette Dieujuste
Purpose: The purpose of this interpretive phenomenological study is to explore the lived experience of Haitian immigrant women living in Massachusetts with PPD. Specific Aims: Aim 1: To explore the lived experience of PPD among Haitian immigrant women. Aim 2: To explore how the experience of being Haitian influences Haitian immigrant women in their response to PPD. Framework: Leininger's Theory of Cultural Care (1988) guided the phenomenological approach and data collection. The Transcultural Care Decision...

Maelstrom Represses Canonical RNA Polymerase II Transcription in Drosophila Dual-Strand piRNA Clusters

Timothy Chang
Transposons constitute much of the animal genome. While many transposons are ancient and inactivated, numerous others are intact and must be actively repressed. Uncontrolled transposons can cause genomic instability through DNA damage or mutations and must be carefully silenced in the germline or risk sterility or mutations that are passed on to offspring. In Drosophila melanogaster, 23–30 nt long piRNAs direct transposon silencing by serving as guides for Aubergine, Argonaute3, and Piwi, the three fly...

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