Stephen Holly

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Stephen Holly

Associate Professor of Pharmaceutical Sciences

Personal profile

About

My research has progressed from a general interest in molecular signaling pathways that regulate important biological events such as cell adhesion and growth to a more focused analysis of signaling pathways that regulate human platelet and megakaryocyte activation during normal blood clotting (hemostasis) or pathological aggregate formation (thrombosis). Precise control of platelet function is crucial for vascular health since excessive activation can lead to ischemic events such as myocardial infarction and stroke, which are still the primary causes of death in the US. While current anti-platelet drugs are effective, they can cause significant bleeding and do not prevent thrombosis in all patient populations, which highlights a need for safer therapeutics that benefit more high-risk groups.

One of my goals has been to identify novel signaling molecules that positively regulate platelet aggregation, one of the primary events in thrombotic disease. In collaboration with others, we discovered an enzyme known as arylacetamide deacetylase-like 1 (AADACL1) in platelets and megakaryocytes using a combination of library screening and innovative chemoproteomic profiling. We found several novel inhibitors that blocked platelet aggregation and secretion and identified the endogenous target of one such inhibitor as AADACL1. We demonstrated that this enzyme is a lipid hydrolase that influences the human platelet lipidome thereby modulating important signal transduction pathways that control platelet activation and potentially thrombus formation. Even though its physiological role and its role in other cell types is not yet clear, AADACL1 represents an intriguing potential drug target for anti-platelet therapies.

Education/Academic qualification

Molecular Cell Biology and Biochemistry, Ph.D., Washington University in St. Louis

… → 1999

Biochemistry, B.S., Clemson University

… → 1992

Disciplines

  • Pharmacy and Pharmaceutical Sciences
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View all 41 Research outputs
  • 3 Other
  • 1 Membership of committee