“Better Health through Discovery, De Novo Design and Targeted Delivery of Novel Drugs!"
Apolipoprotein E (ApoE) is one of the most significant risk factors for late-onset or sporadic Alzheimer's disease. ApoE has been shown to be critical in Aβ clearance from the brain and its ability to do that depends upon its lipidation status. Therefore, there is a growing interest in understanding the underlying mechanisms involved in ApoE lipidation and using these mechanistic understandings to discover drugs to enhance ApoE lipidation status.
Our laboratory is investigating potential involvement of abnormal glucose metabolism in poor ApoE lipidation, leading to decreased Aβ clearance from the Alzheimer's brain.
The p53 protein plays a central role in protecting cells against carcinogenesis. It is inhibited in ~ 50% of human tumors, however, by interaction with the oncogenic Murine Double Minute 2 (MDM2) protein. Therefore, blocking the p53-binding pocket on MDM2 protein by small-molecule drugs, leading to activation of the tumor suppressor p53 protein presents a fundamentally novel strategy against variety of cancers related to different tissue types.
Our laboratory is involved in discovery and design of novel molecules that can mimic the p53 structural features involved in binding to the MDM2 pocket, with the ultimate aim of blocking p53-MDM2 interaction.
Fluspirilene docked into MDM2 binding pocket
MD simulation of fluspirilene-MDM2 complex
Our Research is supported by »
The Alzheimer's Association
W.W. Smith Charitable Trust
Gordon Charter Foundation
National Cancer Institute (NCI)
The School of Engineering, Widener University
George I. Alden Trust
Clinton Global Initiative University Network