Candidiasis has remained the most common opportunistic oral infection in HIV positive individuals and AIDSpatients. Even following the introduction of highly active antiretroviral therapy (HAART) approximately 30% ofAIDS patients acquire oropharyngeal candidiasis (OPC). Candida albicans, the main causative agent of OPC,forms complex aggregated microbial communities, known as biofilms, on host oral mucosal surfaces whichplay an important role in establishing infections called ?oral thrush?. C.

Infectious diseases pose a significant public health burden, accounting for nearly one-fifth of deaths globallyper annum. Most infections are initiated from a restricted mucosal tissue, such as the intestine. To fightintestinal infections, gut-resident immune cells are superior to circulating ones. There is a surge of recentinterest in tissue-resident memory T (TRM) cells that have been shown to be a critical adaptive immunecomponent of mucosal immunity. These cells have been flagged as an ideal cell population to be generated inT cell-based vaccines.

Numerous studies indicate that women and men differ in prevalence of pain disorders or pain intensity,possibly due to sexually dimorphic differences in detection, processing or responses to noxious stimuli. Here,we propose to study a peripheral sexually dimorphic pain mechanism that occurs in humans. The importanceof this complex problem has been emphasized by recent NIH policies (NOT OD 15-102).

Inhibition of the renal SGLT2 transporter has proven to be an effective therapeutic interventionto reduce plasma glucose levels and HbA1c in type 2 diabetic patients. The glycemic-loweringefficacy of the SGLT2 inhibitors results from two distinct mechanisms: (i) induction ofglucosuria, which amounts to ~70-90 grams per day and (ii) amelioration of glucotoxicity leadingto increased insulin sensitivity in muscle and improved beta cell function (JCI 124:509-514,2014).

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major contributors to overall morbidity andmortality in patients in the US. The overall objective of the proposed study is to establish untargeted andtargeted spatial metabolomics analysis of tissues from normal and diseased kidneys to assess cellularmetabolic states associated with healthy function, acute injury, chronic condition, and recovery.

We respond to PQ3 with our data showing that tumor PD-L1 (CD274, B7-H1) is a major regulator of tumorinflammatory infiltrates. Our preliminary data show that melanoma PD-L1 regulates TIL through severalpreviously unknown tumor-intrinsic and extrinsic mechanisms. We define novel effects of tumor intrinsic PD-L1signaling on tumor proliferation, sensitivity to immune killing, in vivo growth independent of anti-tumorimmunity, and regulation of mTOR signals.

Estrogen receptor (ER)? exhibits an antitumor activity in multiple cancer types in both tumor-intrinsicand -extrinsic manners. However, little is known as to how such activity can be harnessed with high efficacyand precision, nor is it clear which host cell type(s) mediates the tumor-extrinsic function of ER?. These majorknowledge gaps hamper efforts to unleash ER? antitumor activity for cancer therapies. We recently discovereda phosphotyrosine-dependent signaling axis that controls ER? antitumor activity.

Uterine fibroids (UFs; leiomyomas) are the most important benign neoplastic threat to women's healthworldwide, but disproportionately affect women of color, particularly African American (AA) women, who have athreefold higher incidence rate and relative risk of UFs than Caucasian (CC) women. While the underlyingcause for this risk disparity is not fully understood, recent studies implicate hypovitaminosis D as a majorcontributor.