Jagadananda Ghosh, PhD

Member of the Henry Ford Cancer Institute

Biographical Statement

Dr. Ghosh is a senior scientist at the Henry Ford Vattikuti Urology Institute. He directs research on cancer cell biology, target based anticancer drug development, and in vivo drug testing using cell lines, xenografts and PDX models. He analyzes specific roles of genes by generating transgenic mice.

In addition, he is responsible for hiring, training and supervising post-doctoral fellows. He writes, reviews and manages grants for research funding, and edits manuscripts for peer reviewed publications. He reviews grants and papers and serves as Editorial Board Member for several journals.

Dr. Ghosh has patents on anticancer drugs and has secured several significant federal and non-federal research grants.

Research Interests

• How MK591 (Quiflapon), a 5-lipoxygenase inhibitor, kills pancreatic cancer cells and downregulates protein kinase C-epsilon: Pancreatic tumors and cell lines derived from them exhibit elevated expression of 5-lipoxygenase (5-Lox), whereas non-tumor glands or normal cells do not exhibit this overexpression. Arachidonic acid stimulates pancreatic cancer cell growth via metabolic conversion through the 5-Lox pathway, and inhibition of 5-Lox activity decreases the viability of pancreatic cancer cells. However, the downstream signaling mechanisms through which 5-Lox exerts its effects on the survival of pancreatic cancer cells remain to be elucidated. Dr. Ghosh's laboratory findings indicate that inhibition of 5-Lox interrupts an Akt-independent, PKCε-dependent survival mechanism in pancreatic cancer cells and suggest that metabolism of arachidonic acid through the 5-Lox pathway plays an integral part in the survival of pancreatic cancer cells via signaling through PKCε, an oncogenic, pro-survival serine/threonine kinase.
• Daclatasvir, an antiviral drug, downregulates Tribbles 2 pseudokinase and resensitizes enzalutamide-resistant prostate cancer cells: FDA-approved enzalutamide is commonly prescribed to reduce the growth of advanced prostate cancer by blocking androgen receptor function. However, enzalutamide-resistant prostate cancer (ERPC) invariably develops and progresses to metastatic, lethal disease. Management of ERPC poses a special problem not only because available therapeutic regimens cannot effectively kill ERPC cells but also due to their propensity to invade large bones. Moreover, molecular mechanism(s) behind enzalutamide resistance is not properly understood, which is delaying development of newer agents. Dr. Ghosh's team found that the pseudokinase, Tribbles 2 (TRIB2), is overexpressed in ERPC cells and plays a critical role in their survival. 
• Tribbles 2 pseudokinase confers enzalutamide resistance in prostate cancer by promoting lineage plasticity: Enzalutamide, a second-generation antiandrogen, is commonly prescribed for therapy of advanced prostate cancer, but enzalutamide-resistant, incurable, lethal, disease invariably develops. To better understand the molecular mechanism(s) behind enzalutamide resistance Dr. Ghosh's team comprehensively analyzed a range of prostate tumors and clinically relevant cell models by gene expression array, immunohistochemistry, and Western blot, which revealed that overexpression of Tribbles 2 (TRIB2) confers enzalutamide resistance in prostate cancer cells via lineage plasticity and cellular trans-differentiation. 

Email: jghosh1@hfhs.org