Mayer-Rokitansky-Küster-Hauser (MRKH) is a rare Disorder of Sexual Development (DSD) that results in the lack of a uterus and vagina in women. Receiving this diagnosis during adolescence can cause various forms of psychological distress in patients and families.<br/>Specifically, this condition could affect a women’s gender identity, body image, romantic relationships, family relationships, and psychological wellbeing. Parents are also put in a stressful<br/>position as they now have to navigate the healthcare system, disclosure, and the relationship with their child. This study aims to expand the knowledge of psychosocial adjustment by studying body<br/>image, gender identity, and mental health in individuals living with MRKH as well as parental disclosure, parental support systems, and parental perceptions of their child’s mental health.
Alzheimer’s disease is a disease that can affect cognition, perception and behavior and is currently untreatable. It was discovered in the early 20th century and while significant scientific advancements have occurred, there is ambiguity that remains to be researched and understood. Latinos are the largest ethnic minority in the United States and while data still needs to be uncovered, possible risk factors for developing Alzheimer’s include heart issues, poverty and obesity, age and education level, to name a few. Poverty is linked to obesity, diabetes and a low education level, which in turn have been found to have an impact on Alzheimer’s and all factors impact cardiovascular and vascular health. Due to the collectivistic culture that is deeply rooted in Latinos, there is a strong sense of family that is upheld when caring for relatives who are afflicted and may be hesitant to receive the care that is needed. Other barriers include financial stability, linguistic and cultural barriers, underutilizing resources and health literacy. There are still research gaps that are yet to be filled like brain health and longitudinal studies for Latinos, but current treatments like diet and culturally competent professionals can help with the prognosis. Alzheimer’s is a complex disease, but with the numerous efforts made thus far, such as creating the LatinosAgainstAlzheimer’s Network, it will soon be able to be understood and hopefully eradicated.
Minocycline is a tetracycline class broad spectrum antibiotic commonly used to treat severe acne and other skin infections. Propranolol is a beta blocker type heart medication primarily used to treat high blood pressure and irregular heartbeat. Chlorpromazine is a phenothiazine antipsychotic usually used for schizophrenia. Metformin is the most widely used first-line oral treatment for type-2 diabetes. Based on a literature survey, minocycline is expected to prevent the phosphorylation of STAT3, a transcription factor downstream of EGFR; propranolol is expected to disrupt EGFR trafficking; chlorpromazine is expected to target the PI3K/mTOR/Akt signaling pathway; metformin is believed to exploit vulnerabilities in cancer cell metabolism, as well as upregulate AMPK against the PI3K/mTOR/Akt pathway.
Efficacy of minocycline in inhibiting EGFR-driven STAT3 activation was investigated using western blot analysis. Our results demonstrate that Minocycline effectively inhibits activation of EGFR-driven STAT3 in U373 glioma cells at 100μM. The ability of chlorpromazine to inhibit the PI3K/mTOR/Akt pathway was similarly tested via western blot, which showed inhibition of phosphorylated Akt and S6 at 10μM. Efficacy of propranolol in perturbing EGFR trafficking was evaluated using flow cytometry and immunofluorescence, which failed to depict altered membrane-associated EGFR abundance. Finally, concentration-dependent inhibition of colony formation was tested for all four drugs. Propranolol and minocycline showed potential biphasic stimulatory effects at 10μM, but all drugs inhibited cell growth at 50μM and higher. Efficacy of these drugs in the treatment of GBM is being further evaluated using in vitro neurosphere cultures from patients identified as having the cellular vulnerabilities potentially targeted by these drugs. Successful completion of this project will lead to in vivo efficacy testing of these four drugs in orthotopic GBM PDX models.
Vaccines are one of the most effective ways of combating infectious diseases and developing vaccine platforms that can be used to produce vaccines can greatly assist in combating global public health threats. This dissertation focuses on the development and pre-clinical testing of vaccine platforms that are highly immunogenic, easily modifiable, economically viable to produce, and stable. These criteria are met by the recombinant immune complex (RIC) universal vaccine platform when produced in plants. The RIC platform is modeled after naturally occurring immune complexes that form when an antibody, a component of the immune system that recognizes protein structures or sequences, binds to its specific antigen, a molecule that causes an immune response. In the RIC platform, a well-characterized antibody is linked via its heavy chain, to an antigen tagged with the antibody-specific epitope. The RIC antibody binds to the epitope tags on other RIC molecules and forms highly immunogenic complexes. My research has primarily focused on the optimization of the RIC platform. First, I altered the RIC platform to enable an N-terminal antigenic fusion instead of the previous C-terminal fusion strategy. This allowed the platform to be used with antigens that require an accessible N-terminus. A mouse immunization study with a model antigen showed that the fusion location, either N-terminal or C-terminal, did not impact the immune response. Next, I studied a synergistic response that was seen upon co-delivery of RIC with virus-like particles (VLP) and showed that the synergistic response could be produced with either N-terminal or C-terminal RIC co-delivered with VLP. Since RICs are inherently insoluble due to their ability to form complexes, I also examined ways to increase RIC solubility by characterizing a panel of modified RICs and antibody-fusions. The outcome was the identification of a modified RIC that had increased solubility while retaining high immunogenicity. Finally, I modified the RIC platform to contain multiple antigenic insertion sites and explored the use of bioinformatic tools to guide the design of a broadly protective vaccine.
