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Debananda Pati, PhD
Professor Debananda 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 cohesin complex proteins and 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 laboratory 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 the 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. The long-term goal of the Pati laboratory is to further advance the understanding of the underlying biology of cohesin and separase in human malignancies, and to translate their discoveries from basic research into clinical applications. Towards that goal, his laboratory has identified five small molecular inhibitors of separase enzymatic activity (called Sepins) to treat separase-overexpressed refractory breast tumors, and several compounds targeting cohesin STAG2 mutant Ewing sarcoma and Down syndrome acute myeloid leukemia (AML) in children. Pati and his colleagues have initiated IND-enabling studies to test these compounds in preclinical studies. This work has funded by the Cancer Prevention and Research Institute of Texas (CPRIT), the Department of Defense and Kate Amato Foundation. A start-up company called Sepin Biotech has been formed by the Baylor College of Medicine to commercialize this product.
Professor Pati has authored 58 primary, peer-reviewed research articles, six book chapters, two peer reviewed commentaries, one patent and numerous abstracts presented at prestigious conferences.
Professor Pati’s laboratory is part of the Cancer Genetics and Genomics Program and the Solid Tumor Program’s sarcoma research laboratories.
Zhang N, Ge G, Meyer, R, Basu, D., Sethi, S., Pradhan, S., Zhao Yi-Jue, Li X-N, Cai WW, El-NaggarAK, Baladandayuthapani V, Kittrell FS, Rao P, Medina D, Pati D. (2008) Overexpression of Separase induces aneuploidy and mammary tumorigenesis Proc Natl Acad Sci U S A 105(35):13033-8. (With highlights in SciBX 2008, 1(30):11 and Cell Cycle). PMC2529090.
Zhang, N., Kuznetsov S., Sharan, SK., Li, K., Rao, PH., and Pati, D. (2008). A Handcuff Model for the Cohesin Complex. Journal of Cell Biology 183(6):1019-31. Faculty of 1000 recommended
Mukherjee M, Ge G., Zhang N, Edwards D, Sumazin, P., Sharan, S, Rao PH, Medina D, Pati D. (2014). MMTV-Espl1 Transgenic Mice Develop Aneuploid, Estrogen Receptor Alpha (ERα)-Positive Mammary Adenocarcinomas. Oncogene 48(33):5511-22. PMC4032816
Zhang N, Scorsone K, Ge G, Kaffes CC, Dobrolecki LE, Mukherjee M, Lewis MT, Berg S, Stephan CC and Pati D. (2014). Identification and characterization of Separase Inhibitors (Sepins) for Cancer Therapy. J. Biomolecular Screening 19(6):878-889. PMID: 24525869
Kumar P, Cheng H, Paudyal S, Nakamura LV, Zhang N, Li JT, Sasidharan R, Jeong M, Pati D. (2020). Haploinsufficiency of cohesin protease, Separase, promotes regeneration of hematopoietic stem cells in mice. Stem Cells. 2020 Sep 30;. doi: 10.1002/stem.3280, PMID: 32997844
Zhang N, Lin K-F, Yang C, Peruski S, Pati D*, Gilbertson SR* (2022). Synthesis and Evaluation of a Class of Compounds Inhibiting the Growth of Stromal Antigen 2 (STAG2)-Mutant Ewing Sarcoma Cells. ChemMedChem, In Press. (*corresponding authors)
2019 Research Award for Cancer in Children and Adolescents, CPRIT
2016 Research Award for Cancer in Children and Adolescents, CPRIT
2014 CPRIT Bridging the Gap Early Translational Award
2010 Faculty Recognition Award (mentoring), Texas Children's Cancer and Hematology Center, Baylor College of Medicine
2008 Virginia & L.E. Simmons Family Foundation Collaborative Research Award
2006 Distinguished Alumni Award, Orissa University of Agriculture & Technology
2001 US Army Medical Research & Material Comm. Career Development Award
1999 The Leukemia and Lymphoma Society Special Fellowship
1998 LI-COR Biotechnology Long Read Sequencing Contest Prize
1996-1999 US Army Breast Cancer Research Program Postdoctoral Fellowship
1993-1994 Minister of Advanced Education International Education Award, Canada
1993 Bettina Bahlsen Memorial Graduate Scholarship
1986-1988 British Overseas Development Administration Shared Scholarship
1986 Best Graduate Gold medal, Orissa University of Agriculture & Technology
US Patent: Pati D. and Zhang N. Separase Inhibitors and Uses Thereof (Id# 61892911, filed on October 18, 2013. Patent issued on August 21, 2018.
Invited Guest Editor Special Issue entitled "Role of Chromosomal Cohesion and Separation in Health and Disease", in collaboration with "International Journal of Molecular Sciences" (IJMS; 2021)
* Texas Children's Hospital physicians' licenses and credentials are reviewed prior to practicing at any of our facilities. Sections titled From the Doctor, Professional Organizations and Publications were provided by the physician's office and were not verified by Texas Children's Hospital.