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Improvements in the detection and treatment of breast cancer have dramatically altered its clinical course and outcome. However, prevention of breast cancer remains an elusive goal. Parity, age of menarche, and age at menopause are major risk factors drawing attention to the important role of the endocrine system in determining the risk of breast cancer,(More)
Alzheimer’s disease (AD) is the leading cause of dementia among the elderly. Disease modifying therapies targeting Aβ that are in development have been proposed to be more effective if treatment was initiated prior to significant accumulation of Aβ in the brain, but optimal timing of treatment initiation has not been clearly established in the clinic. We(More)
Cleavage of the Notch receptor via a γ-secretase, results in the release of the active intra-cellular domain of Notch that migrates to the nucleus and interacts with RBP-Jκ, resulting in the activation of downstream target genes. This canonical Notch signaling pathway has been documented to influence T cell development and function. However, the mechanistic(More)
Severe aplastic anemia (AA) is a bone marrow (BM) failure (BMF) disease frequently caused by aberrant immune destruction of blood progenitors. Although a Th1-mediated pathology is well described for AA, molecular mechanisms driving disease progression remain ill defined. The NOTCH signaling pathway mediates Th1 cell differentiation in the presence of(More)
T cell stimulation requires the input and integration of external signals. Signaling through the T cell receptor (TCR) is known to induce formation of the membrane-tethered CBM complex, comprising CARMA1, BCL10, and MALT1, which is required for TCR-mediated NF-κB activation. TCR signaling has been shown to activate NOTCH proteins, transmembrane receptors(More)
Studies of notch signaling in immune cells have uncovered critical roles for this pathway both during the differentiation and effector function phases of immune responses. Cells of the myeloid lineage, including macrophages and dendritic cells, function as key components of innate immune defense against infection and, by acting as antigen presenting cells,(More)
Th1 and Th17 are subsets of CD4 + T cells or T helper cells (Th). Th cells are the major adaptive immune cells involved in inflammation during the development of Multiple Sclerosis (MS). MS is a neurodegenerative autoimmune disease and one mouse model of the disease is Experimental Autoimmune Encephalomyelitis (EAE). Development and differentiation of Th1(More)
  • Christina M Kuksin, Christina Arieta Kuksin, Lisa M, Barbara A Minter, Wilmore C Osborne, Juan Webley +4 others
  • 2015
DEDICATION To my loving and supportive family v ACKNOWLEDGEMENTS The writing of this dissertation has caused long periods of reflection of my time and accomplishments at UMass Amherst, and the phrase, " it takes a village " keeps flashing through my mind. I would like to take this time to thank my 'village,' without whom I would have never completed this(More)
An association between certain autoimmune conditions and increased risk of developing lymphoma is well documented. Recent evidence points to NOTCH signaling as a strong driver of autoimmunity. Furthermore, a role for NOTCH in various lymphomas, including classical Hodgkin lymphoma, non-Hodgkin lymphoma, and T cell lymphoma has also been described. In this(More)
  • Lisa M, Sandra L Minter, Wilmore C Petersen, Rafael A Webley, Fissore, Salem Ala 'a +4 others
  • 2014
DEDICATION " Bear in mind that the wonderful things you learn in your schools are the work of many generations. All this is put in your hands as your inheritance in order that you may receive it, honor it, add to it, and one day faithfully hand it on to your children. "-Albert Einstein Dedicated to my loving husband, Basel Assaf, for his everlasting support(More)