Dr. Little's research interests include immunology and chronic infection associated with diseases of aging, specifically the role of the immune system in modulating disease severity. One research focus includes the identification of elements of the immune system critical in the prevention of dissemination of the respiratory pathogen, Chlamydia pneumoniae, to extra-respiratory sites. He has published articles pertaining to the forementioned topic as well as investigating the role of Chlamydia pneumoniae infection in the induction of Alzheimer-like pathology in a non-transgenic mouse model of experimentally induced AD-like pathology. The experimental induction of Alzheimer-like pathology in non-transgenic mice serves as a model to study early developments and inducing factors that may lead to symptomatic illness for the sporadic/late onset form of Alzheimer's disease.

Additionally, Dr. Little’s research interests include the study of severe/life-threatening food allergy, particularly life-threatening allergic reactions following consumption to peanuts. These studies involve identifying key immune cells responsible for immune-modulation of the allergic response to peanut and then reprogramming these cells to ameliorate this condition. Dr. Little is a member of The New York Academy of the Sciences, The Alzheimer’s Association, The Microscopy Society of America and Sigma Xi Scientific Research Society.