Dr. Nitai C. Hait joined the faculty in 2016 as an Assistant Professor of Oncology in the Division of Breast Surgery, Department of Surgical Oncology, and Department of Molecular and Cellular Biology at Roswell Park Comprehensive Cancer Center.
Dr. Hait trained as a molecular biologist at the Bose Institute in Calcutta, India and earned his doctoral degree in the field of Biochemistry and Molecular Biology at the Jadavpur University in Calcutta, India. Dr. Hait did his postdoctoral trainings at the University of Kentucky College Of Medicine in Lexington, Kentucky and at the Virginia Commonwealth University School of Medicine, and the Massey Cancer Center in Richmond, Virginia, where he became an Assistant Professor at the Department of Biochemistry and Molecular Biology.
Dr. Hait’s laboratory focuses on following areas:
1) Understanding the role and underlying molecular mechanism of bioactive sphingolipids in cancer progression
2) The role of nuclear receptors signaling in cancer progression
3) The role and underlying molecular mechanism of epigenetic signaling in cancer progression
Dr. Hait’s research in the past several years was focused on sphingolipids signaling in pathophysiology. During his research career he demonstrated many functions of sphingosine-1-phosphate (S1P), which is crucial for pathophysiology. His scientific efforts directed towards understanding the intracellular function of S1P via direct targets independent of its cell surface receptors. He showed that nuclear S1P binds to histone deacetylases (HDACs) and modulates their activity, thus linking S1P and sphingolipid metabolism in the nucleus to gene expression and epigenetic regulation (Science 2009). He also demonstrated that nuclear S1P generated from SphK2 epigenetically regulates genes important for memory functions in mice (Nat Neurosci 2014). In continuation of the research, Dr Hait showed that intracellular S1P generated from SphK1 play a direct role in TNF-α signaling and the canonical NF-kB activation pathway which is important in inflammation and cancer (Nature 2010). Dr. Hait’s collaboration further showed that bile acid signaling via S1PR2 and SphK2 generates nuclear S1P epigenetically regulates lipid metabolism related genes in hepatocytes, important for non-alcoholic fatty liver disease progression (Hepatology 2015). Another avenue of his research focuses that intracellular S1P production worsens high fat diet mediated breast cancer progression. (Oncogenesis 2015). Long term goal of his research program is to explore the role of sphingolipids, nuclear receptors, and epigenetic factors in cancer progression and target them for effective cancer therapy.
Hait NC, Allegood J, Maceyka M, Strub GM, Harikumar KB, Singh SK, Luo C, Marmorstein R, Kordula T, Milstien S, Spiegel S. Regulation of Histone Acetylation in the Nucleus by Sphingosine-1-Phosphate. Science, 2009, 325(5945):1254-7. PMID: 19729656.
Alvarez SE, Harikumar KB, Hait NC, Allegood J, Strub GM, Kim E, Maceyka M, Jiang H, Luo C, Kordula T, Milstien, Spiegel S. Sphingosine-1-phosphate: a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature, 2010, 465(7301):1084-8. PMID: 20577214.
Liang J, Nagahashi M, Kim EY, Harikumar KB, Yamada A, Huang WC, Hait NC, Allegood JC, Price MM, Avni D, Takabe K, Kordula T, Milstien S, Spiegel S. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell, 2013, 14; 23(1):107-20. PMID: 23273921.
Harikumar KB, Yester JW, Surace MJ, Oyeniran C, Price MM, Huang WC, Hait NC, Allegood JC, Yamada A, Kong X, Lazear HM, Bhardwaj R, Takabe K, Diamond MS, Luo C, Milstien S, Spiegel S, Kordula T. K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5. Nat Immunol, 2014, 15(3):231-8. PMID: 24464131.
Hait NC, Wise LE, Allegood JC, O’Brien M, Avni D, Reeves TM, Knapp PE, Lu J, Luo C, Miles MF, Milstien S, Lichtman A, Spiegel S. The active phosphorylated form of Fingolimod inhibits histone deacetylases and facilitates fear extinction memory. Nat Neurosci, 2014, 17(7):971-80. PMID: 24859201.
Donoviel MS, Hait NC, Ramachandran S, Maceyka M, Takabe K, Milstien S, Oravecz T, Spiegel S. Spinster 2, a sphingosine-1-phosphate transporter, plays a critical role in inflammatory and autoimmune diseases. FASEB J. 2015, 29(12):5018-28. PMID: 26324848.
Hait NC#, Avni D, Yamada A, Nagahashi M, Aoyagi T, Aoki H, Dumur CI, Zelenko Z, Gallagher EJ, Leroith D, Milstien S, Takabe K, Spiegel S#. The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer. Oncogenesis, 2015, 4:e156. PMID: 26053034. [#corresponding author]