Cells frequently face adverse conditions such as toxic substances or a lack of nutrients, and they respond by altering protein synthesis and the expression of their genes in order to ensure their survival. The research in this proposal will reveal how this occurs by studying the regulation of the protein synthesis machinery in response to cellular stresses. Misregulation of these cellular processes is common in both cancer and aging.

Arsenic is an environmental carcinogen the effects 200 million people worldwide. Yet, the underlying cause of arsenic mediated carcinogenesis remains without a molecular explanation. These studies will explore the relationship between redox and protein homeostasis and how this can lead to arsenic-derived tumors.

In adults living with HIV (ALHIV), cigarette smoking is the single largest reversible risk factor for cardiovascular disease (CVD), which is a major cause of morbidity and mortality in this population. Poor sleep is also independently associated with CVD risk and linked to decreased success with smoking cessation. The purpose of our award is to evaluate whether a sleep training approach combined with standard smoking cessation therapy (varenicline) will improve smoking cessation in ALHIV smokers who would like to quit smoking. Our study will compare the supplementary sleep training intervention to a general health training intervention in effectiveness in smoking cessation in 200 ALHIV smokers. Implementing a sleep training approach to existing smoking cessation treatments could potentially improve success rates for smoking cessation, thus creating a new avenue to reduce CVD risk in ALHIV. We are being recognized for this award for our unique approach to improving the health of ALHIV through collaboration with multiple disciplines of health.

There is widespread consensus that lesions to the human medial temporal lobes result in a profound loss of long-term verbal memory, termed "amnesia." A growing body of research, however, challenges this modular view of brain function, suggesting that damage to the human medial temporal lobes also results in deficits in perception, working memory, attention, language, and navigation. Yet how such deficits might arise cannot be accounted for by most contemporary models of medial temporal lobe function. Here, we propose a new model of medial temporal lobe function that relies on two independent dimensions: representational precision and binding. We will test this model with patients who have lesions to their medial temporal lobes as a result of stroke and hypoxia and with patients who are scheduled to undergo surgeries to treat epilepsy. The expected outcomes of this grant will provide a more complete account of the effects of damage to the human medial temporal lobes on cognitive function. Our work with patients scheduled to undergo surgery to treat epilepsy can also help predict and potentially address any accompanying cognitive deficits following medial temporal lobe excisions.