Infection from Mycobacterium tuberculosis is the second leading infectious cause of death worldwide after COVID-19, with rates of tuberculosis infection greatest in low and middle-income countries (LMICs). Tuberculous meningitis (TBM) is one of the most severe forms of M. tuberculosis disease with over half of all cases resulting in death or neurological consequences. Recent studies in our lab have found that single-nucleotide polymorphisms (SNPs) in MUC5AC, a secretory lung mucin, are associated with increased TBM susceptibility, morbidity, and mortality. The purpose of my study is to identify the functional MUC5AC SNP. Four candidate SNPs were selected within the MUC5AC promoter region based on high linkage-disequilibrium scores across multiple global populations with a SNP in the MUC5AC promoter, rs28737416. I utilized molecular cloning techniques to combine a luciferase-expressing plasmid with isolated regions of the human MUC5AC promoter containing the SNPs of interest, and subsequently transformed this recombinant plasmid into competent cells. Next, I am performing in-vitro, site-directed mutagenesis to investigate how genotypic variation in each candidate SNP influences promoter function by measuring luciferase expression. I anticipate variants in at least one SNP of interest will reduce gene expression (measured by luciferase expression), indicating functionality. Characterization of this genetic mutation will provide insight into TBM susceptibility across populations and could inform studies of novel therapeutics to treat TBM.


HIV-2 represents approximately 1-2 million of the 38.4 million people living with HIV (PLHIV) worldwide. Existing guidelines and recommendations for the treatment of HIV-2 infection are largely derived from in vitro data and small-scale clinical studies, and are often extrapolated from studies of people living with HIV-1. Furthermore, of the two most common HIV-2 groups (A and B), only a few examples of drug resistance in group B have been reported in literature. As a result, in-depth knowledge about the mutations that arise in group B HIV-2 isolates and the roles that these mutations play in antiretroviral drug resistance is lacking. The aims of my project are (1) to develop a novel approach for creating full-length, infectious HIV-2 group B clones that encode patient-derived integrase sequences, and (2) to demonstrate that this approach can be used to characterize resistance to Integrase Inhibitors (INI), which are an important class of antiretroviral drugs. Specifically, the parental plasmid for cloning and virus expression is 7312A-JK; this plasmid contains a full-length HIV-2 genome with group B gag and pol gene sequences. To facilitate downstream steps, I have replaced the integrase-encoding portion of p7312A-JK pol with a short, synthetic linker. This cassette clone will serve as the acceptor for longer, synthetic DNA fragments that encode patient-derived group B HIV-2 integrases. My ultimate goal is to generate a panel of 10 replication-competent group B clones that can be given to members of the Gottlieb lab for culture-based drug susceptibility testing. This work is an essential step toward a more comprehensive knowledge of drug resistance in HIV-2 which, in turn, is important for evidence-based treatment of all HIV-2–infected individuals, including those infected with group B strains.

The main objective of HIV treatment is reducing mortality and morbidity for people living with HIV and preventing new infections. Accessing and maintaining chronic HIV care is critical for patient wellness and preventing new infections. A normal and healthy quality of life with a reduced chance of transmission can be achieved by maintaining a clinically undetectable viral load, which is directly dependent on regular medical appointments with a primary care provider and adherence to antiretroviral therapy. For patients experiencing significant socioeconomic barriers, maintaining an undetectable viral load is difficult. To help overcome these barriers, our clinic provides patients with higher needs interventions to help them regularly attend medical appointments and obtain medications. This descriptive study examines the effectiveness of offering low threshold healthcare by examining viral loads, socioeconomic factors, and experiences of a group of 100 patients with varying levels of need who are receiving treatment at the MAX clinic in Tacoma, WA since August of 2021. We selected consenting participants who met eligibility by being currently enrolled with a detectable viral load within a year of the study start date. One group, designated as having lower levels of need, consists of those with a history of adhering to care and with no significant socioeconomic or circumstantial barriers for accessing treatment. The second group consists of those with higher needs who have a history of non-adherence to care due to socioeconomic factors, substance use, or circumstantial crisis. We are collecting quantitative and qualitative data from regular HIV test results and interviews conducted every six months. Interviews focus on participants’ experiences with HIV healthcare, situational developments, and patient-centered outcomes. Preliminary results of this study support a low-barrier care model contributes to undetectable viral loads by helping patients with higher needs regularly attend medical appointments and adhere to antiretroviral therapy.

In recent years the field of global health has been plagued by accusations of “neocolonialism.” Rather than genuine involvement in health research, physicians and public health researchers in Global South countries are relegated to menial positions in the research pipeline, and local priorities are not reflected in the research that receives the bulk of international funding. The multilateral donors which fund and manage this research are said to devalue the contributions of Southern researchers, who, many studies of global health journals have shown, are not allowed to take on leadership roles in public health research “collaborations” with Western institutions. Moreover, a large critical literature has characterized the field of global health as taking a narrowly conceived, “vertical” view of health in developing countries. This biomedical/technological bias leads donor-funded research to neglect the social determinants of health and illness. The current project contributes to our understanding of the origins and practical manifestations of these institutional biases of health research in Uganda. A historical analysis of colonial medicine in Uganda was conducted and it was found that medical research in Uganda indeed has historically neglected to address the social determinants of health such as poverty, labor conditions, and the presence or absence of social infrastructure (e.g., roads and sanitation systems). In addition, a review of recent COVID-19, Ebola, and HIV/AIDS research confirms the hypothesis of other scholars that donor-driven public health research tends to treat health in isolation from the larger political economy of development, and is biased toward a highly biomedicalized view of health. I conclude by offering an interpretation of these biases and how they vary by individual donor, as well as some suggestions as to what can be done to make Ugandan health science genuinely equitable and responsive to local, rather than Western, needs.

Oral tolerance to antigens is a mechanism by which immune responses are inhibited to prevent chronic inflammation and tissue damage in response to common exposures, such as dietary antigens or commensal bacteria. Regulatory T cells (Tregs) are an important cell type in such regulation of immune responses, especially in the intestines. There is, however, heterogeneity within Tregs, including a subset that expresses the transcription factor RORgt. However, the mechanisms by which RORgt+ Tregs carry out their suppressive function are currently unknown. Intestinal Tregs are induced in the mesenteric lymph nodes (MLNs) by antigen-presenting dendritic cells (DCs) that migrate from the gut. Antigen transfer from DCs to Tregs is crucial for the development of oral tolerance and DCs are largely regarded as being upstream of Tregs. However, it has also been shown that Tregs play a role in DC migration via a CTLA-4-mediated mechanism. Because this DC-Treg relationship is not fully understood with regard to Treg heterogeneity, I have examined the changes in DC populations in a mouse model where the RORgt+ Treg population alone has been ablated. To do this, I developed a new panel of antibodies to use in flow cytometry in order to characterize the subpopulations of DCs in the intestines and related organs. I harvested and processed murine spleens, MLNs, Peyer's Patches, and small intestine lamina propria in order to compare the populations systemically and locally. I anticipate seeing fewer DCs in the mice lacking RORgt+ Tregs and more DCs in the small intestine and Peyer's patches. This work furthers our understanding of the intricacies of the intestinal immune system. This knowledge can be applied to vaccine research, as RORgt+ Tregs have been implicated as suppressors of immune response to oral vaccines. Intestinal immunity is also of interest in allergy and gut inflammation research.