Faculty Profile

Dr. Bogos Agianian, Ph.D.

Bogos Agianian, Ph.D.

Research Assistant Professor, Department of Biochemistry

Areas of Research: Structural biology, drug discovery, molecular biophysics, structure-function, kinases, cancer

Professional Interests

My current research focuses on the understanding of regulation of kinases and phosphatases that mediate aberrant signaling in melanoma, colorectal and other cancers.  A main goal is to design and validate novel small molecule inhibitors and modulators of these oncogenic enzymes, which have therapeutic potential. Moreover, I work on other disease targets and on the structural basis of activation of pro-apoptotic protein BAX. To answer research questions, I apply a combinatorial approach using X-ray crystallography, computational drug design and a battery of biochemical and biophysical techniques. 


Novel BRAF targeting 

Oncogenic mutation V600E in BRAF is found in almost 50% of melanoma tumors. BRAFV600E usually acts as an active monomer in melanoma, however, constitutively active BRAF dimers mediate aberrant signaling and aquired resistance to current BRAF-targeted drug treatment in approximately one in five refractory melanoma cases.    

In light of the key clinical importance of BRAF dimerization in tumors, we initiated a systematic quest for novel small molecule inhibitors that specifically recognize BRAF dimers.  Our BRAF-inhibitor co-crystal structures and rational drug design efforts have produced potent next-generation BRAF inhibitors.  Currently, we vigorously validate and optimize the potency and specificity of these inhibitors in biochemical, biophysical and cellular experiments and work towards obtaining leads with desirable pharmacological targeting of resistant melanoma in vivo.

 

 

Selected Publications

Agianian B*, Gavathiotis E*. Current Insights of BRAF Inhibitors in Cancer. J. Med. Chem. 2018. 

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Albert Einstein College of Medicine
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Research Information