Shantaram Joshi, PhD

Professor, Department of Genetics, Cell Biology and Anatomy at the University of Nebraska Medical Center

Shantaram Joshi, PhD, Mantle Cell Lymphoma (MCL) Consortium member and current recipient of a Lymphoma Research Foundation MCL Research Initiative grant, has recently made some intriguing discoveries in the field of MCL research.

His paper entitled “Targeting of Sonic Hedgehog-GLI Signaling: A Potential Strategy to Improve Therapy for Mantle Cell Lymphoma” has been published as a cover story in the June 2008 issue of Molecular Cancer Therapeutics, a monthly journal published by the American Association for Cancer Research.

“MCL is a very aggressive disease with an overall survival of three to four years following standard therapy,” said Dr. Joshi, Professor in the Department of Genetics, Cell Biology and Anatomy at the University of Nebraska Medical Center. “We need to come up with new treatment modalities for the resistant mantle cell lymphoma so that the patient can survive longer without disease.”

Dr. Joshi and his colleagues (Ganapti Hedge, PhD; Corey Munger, PhD; Timothy Greiner, MD; Dennis Wiesenburger, MD; and Julie Vose MD) set out to gain a better understanding of the underlying mechanisms that regulate MCL proliferation and survival by examining the role of sonic hedgehog (Shh)-GLI signaling, a biological pathway associated with cell division of stem cells. Shh-GLI signaling has been implicated in the development of several forms of cancer, but no such study has been published on its link with MCL development—until now.

In the laboratory, Dr. Joshi was able to show that molecules associated with Shh-GLI signaling were expressed in human MCL cells, and by altering the signaling pathway one could control cancer cell proliferation. Specifically, down-regulating GLI resulted in significantly decreased proliferation of the MCL cells and increased susceptibility to doxorubicin, a chemotherapeutic drug. These findings implicate the therapeutic potential of the Shh-GLI signaling pathway in treating MCL.

Dr. Joshi has initiated similar studies in mouse models and is awaiting publication of these results. A Phase I/II clinical trial targeting the Shh-GLI is expected to begin recruiting patients upon completion of the preclinical studies.