Shantaram S. Joshi, PhD
Shantaram S. Joshi, PhD is a member of the Lymphoma Research Foundation's (LRF) Mantle Cell Lymphoma Consortium (MCLC), is medical and graduate student professor in the Department of Genetics, Cell Biology and Anatomy in the College of Medicine at University of Nebraska Medical Center (UNMC), and is a 2005 LRF Mantle Cell Initiative (MCI) grant recipient.
Dr. Joshi received his BS and MSc from the University of Mysore, India and his PhD from the University of Bombay, India. He completed a post-doctoral fellowship in lymphoma biology and metastasis at the Indiana University School of Medicine. He was originally drawn to the field of lymphoma research because of the inspirational individuals he worked with in the leukemia and lymphoma ward at the Tata Memorial Center for Cancer Research and Treatment in Mumbai, India during his PhD studies. "I frequently saw sick children who were confined to the hospital, missing out on every child's prerogative to play outside," he said. "I never forget those kids' faces. For me, they highlight the reason why I have been so driven to pursue leukemia and lymphoma research." Dr. Joshi emphasized that despite current knowledge of the general mechanisms of these diseases, there are still many elusive aspects that impact those inflicted and their families, and further progress is still needed. "While lymphomas have been well studied overall, there are several molecular nuances that continue to make this a challenging field," he said.
Dr. Joshi's MCI grant project sought to optimize dendritic cell-based therapy for MCL and had promising results in eliminating residual MCL cells which regularly cause relapse. "The support from the LRF MCL grant contributed greatly to our group; it made it possible for our team to pioneer the investigation of the role of activated sonic hedgehog signaling in refractory lymphoma, which was found to increase resistance of MCL cells and promote their proliferation," he explained. "Upon understanding this, we used the grant to incorporate targeting of hedgehog signaling through inhibitors in multipronged therapeutic strategy for refractory MCL. This therapeutic approach will be significant since lymphoma relapse is due to therapy resistant cells, which is precisely what the multipronged therapy targets. Thus, thanks to the LRF grant, we were able to develop a method to destroy residual tumors." Dr. Joshi's research group is the pioneer in reporting a role for sonic hedgehog signaling in B-cell lymphoma and their findings were published as a cover story in a 2008 issue of Molecular Cancer Research.
His research is currently focused on trying to elucidate the molecular basis of therapy resistance in MCL. "For this purpose, we have developed seven different stable therapy-resistant MCL cell lines from the liver, kidney and lungs of the preclinical animals bearing parental Granta- 519 MCL," said Dr. Joshi. "These cell lines will be an extremely useful tool that will allow us to further understand the mechanism of therapy resistance in MCL, specifically to identify common molecular features of resistance in these cell lines and also to evaluate whether there are any molecular differences based on the tissue origin."
In the case of newly diagnosed patients, Dr. Joshi always imagines how difficult of a time it is for them and their families. "As a researcher in the field, I would assure them that my team and I will continue to work hard to try and deduce nuances of their disease so we can hopefully come up with therapies that will treat the most resistant forms of lymphoma," he said. "I would also suggest that newly diagnosed patients look into clinical trials where small molecule inhibitors are being used to target a cellular pathway and/or key gene(s) involved in lymphoma progression." Dr. Joshi pointed out that in addition to federal agencies, such as the National Institutes of Health, there are foundations such as LRF that are working to promote awareness of the disease and provide resources to patients and families. "This is a great service for those affected," he said.
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