Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb), kills nearly 2 million people a year and is a major cause of morbidity and mortality worldwide. The increasing prevalence of multi-drug resistant (MDR) strains that fail to respond to all currently available drugs underscores the critical need for new therapeutic strategies. DNA topoisomerases (topos) are a class of enzymes responsible for maintaining the correct topological state of DNA molecules by modulating the degree of supercoiling through the breakage and reforming of covalent phosphodiester bonds in the DNA backbone. With the precedent-setting success of several anticancer and antibacterial drugs that target topos, focus in TB research has increasingly turned to these enzymes as new potential targets for chemotherapy. In this study, we isolated Mtb topoisomerase type IA (MtbTOPA), a subclass that only acts on single-stranded DNA (ssDNA), as our target of interest. At least one type IA topo activity must be present in every organism for resolving topological obstacles that require ssDNA cleavage, and fortuitously, Mtb happens to only encode one type IA, further validating MtbTOPA as a high-value drug target. We have cloned, expressed, and isolated highly purified recombinant MtbTOPA protein for enzymatic studies and work is currently underway to solve its crystal structure to aid in target-based approaches to drug development. In efforts to develop a high-throughput screen (HTS) for identification of small molecule inhibitors of MtbTOPA, we have collaborated with the Global Alliance for TB Drug Development (GATB) and leading structural genomics centers to gain access to large compound libraries as well as to accelerate the drug discovery process. We adopted a HTS method based on fluorescence resonance energy-transfer (FRET) and requisite MtbTOPA mutants were designed. It is our hope that the HTS will identify several hits that can be developed into novel TB drugs.

The prevalence of HIV cases in the African born national population versus the African American or national population in general is notably high. In Washington state, there are approximately four times more HIV cases for the foreign born black male versus the African American black male along with about eleven times more HIV cases for the foreign born black female compared to the African American female counterpart. Stigma can impact medication adherence, quality of treatment and undiagnosed contributing mental disorders that, when treated, can improve one’s HIV status. However, little is known about how HIV stigma impacts the treatment and intervention outcomes for the African-born population. My lab as well as my individual role in this research project aims to analyze the nature of HIV stigma among this population, which will provide fundamentals of an intervention that is most ideal for African born population. We conducted semi-structured qualitative interviews with African born patients receiving treatment at Harborview Medical Center Madison HIV Clinic and those receiving social service at BABES YWCA network, and then I as the primary coder analyzed the data through ATLAS.ti, analytic software. Preliminary results indicate that stress due to community paranoia and disturbances due to family history of HIV are common obstacles faced by this population. These findings have important implications for focusing on treatment and other interventions for this understudied population.

The 21st century has seen the emergence and re-emergence of novel infectious diseases. Following in the footsteps of its communicable predecessors, the recent emergence in Saudi Arabia of a SARS-like novel coronavirus, or Middle East respiratory syndrome (MERS-CoV), since 2012 has weaved narratives of globally interdependent economic, political, and social intimacies. I will examine the contrasting narratives that reflect investigations and responses to this novel threat from Middle Eastern, European, and North American media networks, the WHO, the global biomedical community, and the Saudi Arabian Ministry of Health through several intersecting discourses: intellectual property rights and viral sovereignty; the deliberation on the taxonomy of the novel coronavirus; and geopolitical differences in information sharing and biosecurity in the context of emergent 21st century epidemics. Using Priscilla Wald’s concept of outbreak narratives and the imaginative hold of myths as a framework, I will explore how the stories on the global effort to investigate and respond to the MERS outbreaks continue to be revealed, repackaged, and transformed as experts around the world scramble to uncover its epidemiological pathways. I argue that the consideration of these counter-narratives are critical for rethinking underlying, potentially harmful, factors beyond dominant epidemiological and biomedical discourses surrounding the MERS epidemics. Such considerations may serve as a microcosm for biopolitical barriers in the response to past, present, and future emergent diseases. These counter-narratives should be regarded in light of uncertainties that still cloud the etiology and transmission of the virus which has since infected 243 people and claimed 93 lives in 11 countries in Europe, the Middle East, and Southeast Asia.

Recent developments in research on Human Papillomavirus (HPV) have allowed for an increase of strategies that prevent the onset of cervical cancer within communities of little economic privilege. This project will compare preventative measures taken in India and those currently called for within the U.S., primarily examining how cultural and economic limitations are taken into consideration. As a “space of negation and the socially dead, produced by expropriations and alienations in and outside European nation-states” necropolis or low and middle income countries have historically been perceived as a necessity in order to maintain the priorities set by biopolis. However, organizations such as PATH are beginning to look into more cooperative methods. I will analyze the onset of preventative practices that promote self sufficiency in a format that maintains economic functionality and decreases potential dependency for aid. One significant limitation however is that western corporations still hold much of the control regarding economic leeway of vaccination use and price on a global scale. In this project I explore alternative methods that advocate information as an alternative or supplemental method for prevention. This project will continue by examining how circumstances in low economic environments are taken into consideration through efforts of vaccination or treatment. This includes the incorporation of cultural awareness, provision of knowledge and communication within the community, and how this leads to a stronger awareness of what limitations remain.

This project examines the ethical and social frames which facilitate environmental conditions that fuel the rampage of tuberculosis in India. Three key components of the basic biomedical outbreak narrative that are often overlooked will be brought forth to attention: the tuberculosis outbreak as more than just a bacterial spread, social constructs which shape the bacteria’s accessibility to victims, and socioeconomic determinants of treatment (and lack thereof). India accounts for approximately one-fifth of global tuberculosis occurrences, and with over 2 million cases in the country, tuberculosis is a continuously growing health concern, posing a major threat to the well-being of the population. Due to India's developing health care system, pollution, and poverty, these conditions amplify the ease of transmissibility and rate of infection. As treatment regimens are abandoned due to social stigma, medical side effects, and overwhelming price tags, the bacterium which causes TB (mycobacterium tuberculosis), tends to mutate and become drug-resistant to varying degrees; increasing the difficulty of containment and scientific development of effective medicines. Furthermore, the capitalist structure of the pharmaceutical industry contributes to the financial challenges which prevent the eradication of tuberculosis. Drawing on the theory of biopolitics while using sources of statistical information and analytical discourse,  my presentation seeks to explore various properties of the disease and discover how the complex interconnectedness of these underlying issues attribute to forms of structural violence, perpetuating the growth of tuberculosis in India.