Professor Pati is a highly accomplished cancer biologist who is an internationally recognized leader in the field of chromosomal cohesion and Separation and its role in carcinogenesis. He has a highly impressive track record not only in basic biology of chromosomal cohesion and separation, but devising novel and innovative approaches to target the cohesin pathway for treating refractory human cancers. He is widely recognized nationally and internationally as a creative and innovative scientist and is specifically recognized for his identification and targeting of the cohesin-protease, Separase for cancer therapy. Separase, an enzyme important for resolving chromosomal cohesion, is a novel oncogene and promoter of aneuploidy and tumorigenesis that Professor Pati demonstrated is an ideal target for cancer therapy. His lab was first to show that Separase is an oncogene and aneuploidy promoter. In a series of publications in high impact journals, Professor Pati and his colleagues demonstrated that overexpression of Separase in mouse models not only induces aneuploidy but also results in tumorigenesis. The physiological relevance of these mouse studies was underscored by Pati laboratory's subsequent findings that Separase protein is overexpressed in multiple human tumors including breast, bone, brain and prostate. Greater than 60% of human breast cancers, 50% of triple-negative and 83% of luminal B tumors overexpress Separase. Separase overexpression strongly correlates with a high incidence of relapse and metastasis and a lower 5-year overall survival rate. Professor Pati's studies provide new perspective on aneuploidy and indicate that misexpression of chromosomal segregation proteins represents a mechanism of aneuploidy development, and that aneuploidy may constitute a precursor to tumorigenesis. These results strengthened his hypothesis that tumor cell aneuploidy can be targeted for therapy by inhibiting Separase enzyme activity, which is a major current focus in his laboratory. Towards that goal, his laboratory has identified five small molecular inhibitors of Separase enzymatic activity (called Sepins) and have initiated IND-enabling studies to test these compounds in preclinical studies.
Publications/Creative Works
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