Medicine and Health Sciences Commons^™

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Accelerated Forgetting In People With Epilepsy: Pathologic Memory Loss, Its Neural Basis, And Potential Therapies, Sarah Ashley Steimel Phd

Dartmouth College Ph.D Dissertations

While forgetting is vital to human functioning, delineating between normative and disordered forgetting can become incredibly complex. This thesis characterizes a pathologic form of forgetting in epilepsy, identifies a neural basis, and investigates the potential of stimulation as a therapeutic tool. Chapter 2 presents a behavioral characterization of the time course of Accelerated Long-Term Forgetting (ALF) in people with epilepsy (PWE). This chapter shows evidence of ALF on a shorter time scale than previous studies, with a differential impact on recall and recognition. Chapter 3 builds upon the work in Chapter 2 by extending ALF time points and investigating the …

Relieving Immune Suppression In The Melanoma Tumor Microenvironment, Gretel Torres Santiesteban

Dartmouth College Ph.D Dissertations

The high immunogenicity of melanoma tumors makes these malignancies an attractive target for immunotherapeutic treatment, as evidenced by the success of ipilimumab and nivolumab. However, most immunotherapeutic approaches have had limited success, partly due to the suppression of innate and adaptive immune responses by tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). TAM redirection may relieve immunosuppression in the TME, directly inhibiting melanoma growth and potentially enhancing the efficacy of additional targeted and immuno-therapies.

We have shown that synthetic oleanane triterpenoid CDDO-Me (or C-Me) enhances immune activation in the melanoma TME by reprogramming TAMs from immunosuppressive to immunostimulatory. CDDO-Me is …

Impacts Of Population Level Environmental Contaminants, Sex Hormones, And Fibroblast Cell Subsets On Systemic Sclerosis (Ssc), Noelle N. Kosarek

Dartmouth College Ph.D Dissertations

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibrosis of the skin and internal organs, vascular abnormalities, and autoantibody formation. The etiology of SSc is unknown, though the disease is thought to arise in genetically predisposed individuals after exposure to an environmental factor. There are few FDA approved disease modifying medications available to treat SSc.

The express aims of this dissertation are tripart. First, we aimed to validate a 3D tissue model known as the self-assembled skin equivalent (saSE) model. Second, we sought to describe the geographic distribution of SSc in a US Medicare population to better understand …