The immune system is the body’s beautifully complex defense mechanism. With so many cell types, cytokines, and signaling molecules, it is inevitable that these parts working in harmony will sometimes get their job wrong and harm the body instead of protecting it. The Nicholas Lab studies the origins and impact of chronic inflammation in type 2 diabetes and polcystic ovary syndrome. The long-term research goals of the Nicholas Lab are to understand how the immune system integrates with endocrine organs to promote health or cause disease with the ultimate outcome of identifying druggable targets to improve disease. We use a combination of molecular and cellular biology, transgenic mouse models, cytokine profiling, and flow cytometry to address our research questions.

Antigen Presentation in Type 2 Diabetes

The immune system operates like elite troops in a special military force. Upon invasion from unwanted intruders, immune cells mount a coordinated response to eliminate the threat, usually directed by “presentation” of proteins called antigens. However, these antigens are not always proteins, but can be lipids! The molecules that “present” the majority of lipid antigens to specialized immune cells in humans do not exist in mice, an immunologist’s favorite animal model. In the Nicholas lab, we leverage human samples and transgenic mice expressing human lipid presentation molecules (CD1a, CD1b, and CD1c) to further the world’s knowledge of lipid antigen processing and presentation. Our ambition is to understand how lipid antigen presentation contributes to type 2 diabetes.

Immune Regulation of Reproduction and Polycystic Ovary Syndrome

Gonadotropins are the hormones from the gonadotrope, a cell type in the pituitary, that regulate reproduction and sex steroids. The Nicholas lab has discovered a novel population of immune cells in the pituitary that impact gonadotrope function. The identities and functions of these immune cells remain unknown. Using transcriptomics, multiplexing, and systems biology approaches, our goal is to solve the puzzle of these immune cells. What immune cells are in the pituitary and why? Specifically, how do they regulate reproduction?