Samy Meroueh, PhD

Bio

I received a Ph.D. from the Department of Chemistry at Wayne State University in the laboratory of William L. Hase. There, I explored and developed methods to model intermolecular forces that drive molecular recognition and ensuing chemical reactions in peptides. As a postdoc, I joined the bioorganic laboratory of Dr. Shahriar Mobashery first at Wayne State University and then at the University of Notre Dame. I worked on understanding the mechanism by which β-lactamases hydrolyze β-lactam antibiotics. I also developed mechanism-based covalent small molecules using innovative strategies to inhibit matrix metalloproteinases and cathepsin proteases, which promote tumor invasion and metastasis. In my chemical biology and medicinal chemistry laboratory at Indiana University, we develop small molecules that modulate the function of proteins that are considered undruggable, such as members of the RAS and Rho GTPase superfamily, transcription factors and co-activators such as Hippo pathway TEAD and YAP, and proteins involved in tight protein-protein interactions like the urokinase receptor or the HPV E6 oncogene. To accomplish this, we use innovative strategies that includes developing compounds that engage specific hot spots at protein-protein interfaces, form a covalent bond to irreversibly inhibit the target protein, or degrade proteins using proteolysis targeting chimeras (PROTACs). Small molecules are developed primarily through a fragment-based drug design approach using covalent and non-covalent fragment libraries available in my laboratory, as well as structure-guided drug design strategies based on cocrystal structures that we solve in my laboratory. In addition to my continuous funding from the National Institutes of Health, I was the recipient of a Research Scholar Award from the American Cancer Society (ACS) and served as a reviewer at the ACS drug discovery review panel for 7 years. I also serve ad-hoc on several study sections at the NIH including the drug discovery and molecular pharmacology (DMP) study section. I am a recipient of a Merit Award from the Department of Veterans Affairs. I am a member of the Simon Comprehensive Cancer Center, and the Stark Neurosciences Institute.

Meroueh Lab website

Titles & Appointments

Professor of Biochemistry & Molecular Biology

Education

2001 PhD Wayne State University

1995 BS Wayne State University
Research

In the Meroueh lab we develop small molecules to inhibit the cellular function of well-established oncogenes such as members of the RAS superfamilies, transcription factors such as the TEAD-YAP complex, and protein-protein interactions such as HPV E6 oncogenes and urokinase receptor. We are also interested in targets that prevent recovering following spinal cord and traumatic brain injury, such as the Rho GTPases. To accomplish this, we use innovative strategies such developing small molecules that (i) engage hot spots at protein-protein interfaces, (ii) form a covalent bond with target nucleophiles such as cysteine and tyrosine to irreversibly inhibit the target protein, or (iii) degrade proteins using proteolysis targeting chimeras (PROTACs). Small molecules are developed primarily through a fragment-based drug design approach using covalent and non-covalent fragment libraries available in the Meroueh laboratory. Fragments are improved by structure-guided drug design strategies based on co-crystal structures that we solve in my laboratory. We use a range of biochemical and cell biological approaches to explore the potency and selectivity of small molecules that includes fluorescence-based methods, bioanalytical tools such as surface plasmon resonance, and cell-based assays using standard molecular biology methods, or more sophisticated methods like luciferase-based methods.

Research Labs

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Faculty Labs