Assistant Professor, Biochemistry and Molecular Biology
Phone: 402-559-7754 (Office)
M.V.Sc., Tamilnadu Veterinary and Animal Sciences University
B.V.Sc (DVM)., Acharya NG Ranga Agricultural University
- Identification of miRNA signature for diagnosis and prognosis of pancreatic cancer
- Genetically engineered mouse models with/without mucins to study pancreatic and colorectal cancer pathogenesis.
- Chemoprevention and novel combination therapies for pancreatic and colorectal cancer.
My lab is focused to study pathogenesis and targeting strategies for pancreatic and colorectal cancers through miRNA, natural agents and other novel combination therapies using human and mouse derived cell lines and GEM models. We observed that several microRNAs (miRNAs) are differentially expressed in mouse pancreatic cancer (PC) using KC mouse model. Further, expression of miR-216/217, miR-96, miR-345 and let-7b significantly down regulated during the progression of mouse PC from 10 weeks to 50 weeks of age. Specifically, restoration of miR-345 in PC cells resulted in inhibition of PC cell growth, motility, invasion in vitro and tumor growth and metastasis in vivo. In addition, re-introduction of miR-345 in PC cells resulted in down regulation of SHH, Kras, MUC4, and their downstream signaling pathways. We continue working on this miR-345 to simultaneously target Stroma and to downregulate Kras, and MUC4 mediated signaling to counter the barrier imposed by tumor stroma (desmoplasia) for improved delivery of chemotherapy. Chemotherapeutic agents, commonly used for PC treatment are not effective in inhibiting PC progression and metastasis due to an extensive dense stromal reaction (i.e. desmoplasia) that hinders the drug from reaching the tumor cells. Shh-signaling drives the desmoplasia and metastasis, but deletion of SHH alone in mouse PC resulted in aggressive tumors with reduced stroma and increased proliferation and vascularity. Further, in collaboration with University of IOWA, we developed an innovative nanotechnology with multifunctional nano-carrier formulation of combined delivery of miR-345 with the clinically approved drug GEM. Additionally, lab research also focused to study the role of mucins in cancer pathogenesis and their targeting strategies using cell lines, organoids and genetically engineered mouse models.
Research Opportunities in my laboratory:
Research opportunities are available for highly motivated students. Contact Dr. Rachagani for additional information Email.