With a high attributable mortality rate of 40-50%, Candida species represent the fourth leading cause of hospital-acquired bloodstream infections in the United States. These fungal pathogens are normally found as commensals in mammalian mucosal niches, especially the oral cavity. In immunocompromised patients, Candida overgrowth leads to the formation of biofilms, which play an important role in the development of infection. Biofilms are complex microbial communities that adhere to a surface and are enclosed within an extracellular matrix.

An adverse intrauterine environment, seen in pregnancies complicated by preeclampsia, obesity or intrauterine growth restriction (IUGR), programs the offspring for disease in later life. Placental function regulates fetal growth and development, transducing the maternal and uterine environment to the fetus, and mediating fetal programming. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through translational repression or mRNA degradation.

Environmental exposures such as maternal adiposity mark the placental epigenome which modulates placental function. Pregnancies in obese mothers generate an adverse intrauterine environment, via their inflammatory milieu and metabolic derangements that programs the offspring in a sexually dimorphic manner for obesity, diabetes and metabolic disease in adult life. Understanding the role of the intrauterine environment on epigenetic regulation of placental function is needed to prevent the intergenerational transmission of disease.

Depression is a severe and common mental disorder and often coexists with metabolic disorders such as diabetes. Therefore, the identification and characterization of therapeutic targets that are potentially beneficial for the treatment of both depression and diabetes would be of great clinical significance. Adiponectin, a hormone secreted almost exclusively by white adipose tissue, is well recognized as an anti-diabetic adipokine. We have demonstrated that adiponectin insufficiency increases susceptibility to depression-like symptoms.

Periodontal infection has been shown to increase the incidence and severity of atherosclerosis, which is now the number one cause of morbidity and mortality in the United States. Furthermore there is increasing evidence linking obesity, which is a major risk factor of atherosclerosis, to periodontal disease. In atherosclerosis, the earliest lesions contain macrophages that have phagocytized and accumulated modified lipoproteins. The continued monocyte recruitment and cholesterol accumulation in the vessel wall facilitates chronic disease progression.

The prevalence of diabetes and its complications has increased among older adults, and new models of care are needed to combat this trend among vulnerable populations. According to the Chronic Care Model (CCM), optimal chronic illness care requires linkages with community-based resources. Research based upon the CCM suggests that self-management support for older adults with diabetes may be bolstered by linkages between primary care providers and senior centers, but studies of such linkages are rare.

Sub-optimal glycemic control remains a major barrier to dental implant therapy for diabetes patients. With over 25 million individuals affected in the US, understanding the relationship between glycemic control and implant-related outcomes becomes critical to the development of clinical guidelines for the care of these patients. While emerging evidence demonstrates promise for implant osseointegration independent of glycemic levels, there remains no clear evidence of the effects of glycemic control for implant-related complications under long-term function.

Metabolic disorders including obesity, dyslipidemia and diabetes appear to be associated with monocyte dysfunction, yet the molecular mechanisms underlying monocyte dysfunction in vivo are only poorly understood. Our recent studies showed that metabolic stress promotes the dysregulation and hyper-activation of monocyte responses to chemokines and that monocyte dysfunction is a critical and rate-limiting step in the development and progression of atherosclerosis.

Schistosomes are the most important of the helminth parasites that infect humans. Larval stages infect aquatic snails, so the transmission cycle can be broken by interfering with this stage in the parasite lifecycle. We will use genetic crosses of schistosomes in the laboratory to identify the parasite genes that underlie recognition of snail vectors and development of parasites within host snails.

Subjects with impaired fasting glucose have increased risk of progression to T2DM. The metabolic defects responsible for the increase in FPG within the nondiabetic range have been poorly studied. A clearer understanding of the mechanisms of these defects will help to develop improved strategies to treat and prevent T2DM. We previously have shown that basal glucose clearance is decreased in IFG subjects.