Shantaram S Joshi, Ph.D.

PROFESSOR

Shantaram S Joshi, Ph.D.University of Bombay, India
1979

Phone: 402-559-4165
Fax: 402-559-3400
Email

Teaching Philosophy: As a teacher for professional and graduate students I believe that I must provide:  the main concepts, appropriate levels of content and credible main resources. In addition, to provide active learning flat form, I believe in using self-paced and self-directed tools like e-Modules, team based, case based and/or problem based learning.

Teaching Activities:

I am involved in teaching both medical and graduate students. For medical students, I teach cell and molecular biology, histology including hematopoiesis & immunology and problem-based learning. For graduate students, I teach cell biology, molecular cell biology, and cell cycle/division and cancer biology.

Core/Course Directorship:

Research Activities/Interests:

Overall goals: The long-term goal of our laboratory is to improve therapy for human B lymphocytic malignancies and pediatric cancers by means of translational research involving molecular characterization of progressive/therapy resistant malignant cells.

Tumor Microenvironment in chronic lymphocytic leukemia (CLL). CLL is the most common leukemia of the older population in the United States and rest of Western countries. Resistance to therapy due to CLL cell –favorable alterations in apoptosis and cell cycle regulation is a major problem in clinical management of CLL. Therefore, improvements in existing therapy and/or new effective therapies are essential. Emerging evidence suggest that tumor microenvironment such as lymph nodes play a major role in promoting CLL progression. Using DNA microarray analysis, the differentially-expressed genes in CLL cells from patients or from patients' peripheral blood, bone marrow and lymph nodes were identified. Our results demonstrate that CLL cell in the lymph node promotes CLL progression by inducing CLL proliferation/survival and inhibiting immune response to CLL. Selected differentially-expressed genes were targeted to revert their resistant behavior. Gene-targeted CLL cells (targeting BCR-, MAPK-Erk-signaling) resulted in significantly more effective therapy. Ongoing studies are focusing on the other differentially-expressed genes associated with poor clinical outcome.

Multi-pronged therapy for Mantle Cell Lymphoma (MCL). Mantle cell lymphoma is a very aggressive malignancy of B-cells expressing CD5 and CD20 molecules and characterized by a t(11:14) translocation causing overexpression of Cyclin-C1 and cell cycle dysregulation. MCL is rarely cured with standard-dose chemotherapy. HDT followed by autologous stem cell therapy (ASCT) has been shown to induce long-term remission in MCL. However, relapse occurs due to residual lymphoma cells. Because these residual lymphoma cells are resistant to conventional therapies and tumor burden in the patients is low after HDT, a gene targeting approach followed by an immune-based therapy, such as MCC-specific cytotoxic T cell (CTL) based immunotherapy, might be effective and needs to be evaluated. The main objective of this project is to stimulate DCs in patients against their own tumor cells using autologous dendritic cell-MCL cell hybrid for in vivo immune stimulation to initiate antitumor response via MCL specific CTLs.  We have published our results on the preclinical studies. As a logical next step we are in the process of taking this approach to the clinic with additional molecular studies to characterize therapy-resistant MCL.

Improve Therapy For Pediatric Cancer:  In order to provide better treatment options for the pediatric cancer patients in Nebraska, with the funds from the State of Nebraska, UNMC has initiated Pediatric Cancer Research Program. The main focus of this program is to improve therapy for children with cancer. As a part of this program, relatively recently we have started working on developing improved therapy for Neuroblastoma and Medulolastoma using state of the art gene targeting approach. In this effort we are also investigating the roles of exosomes in regulating Ewing’s sarcoma (EWS) and other aggressive pediatric cancer. While we are attempting to understanding molecular basis of this process, we expect to identify viable therapeutic targets to improve therapy from EWS. 

Publications listed in PubMed

Significant and Selected  Recent Publications

  1. Shukla V, Shukla A, Joshi SS, Lu R. IRF4 functions as an attenuator of Notch signaling during CLL development. Oncotarget, Published on line May 25th, 2016.
  2. Haney SL, Upchurch GM, Opavska J, Klinkebiel D, Hlady RA, Suresh A, Pirruccello SJ, Shukla V, Lu R, Costinean S, Angie Rizzino, Karpf AR, Joshi SS, Swanson P, Opavsky R. "Promoter hypomethylation and expression is conserved in mouse chronic lymphocytic leukemia induced by decreased or inactivated Dnmt3a" Cell Reports, 2016.
  3. Hassan HM, Varney ML, Joshi SS, Weisenburger DD, Singh RK, Dave BJ, Diclofenac induces anti-proliferative and pro-apoptotic activity in Mantle cell lymphoma independent of p53 status, Leukemia and Lymphoma , DOI: 10.3109/10428194.20161165814. 2016.
  4. Chaturvedi NK, McGuire T, Coulter D, McIntire E, Shukla A, Sharp JG , Joshi SS. Optimizing Therapy for Neuroblastoma: A Combination Approach with Targeted Therapy. Oncotarget, Published online February 2016
  5. Shukla A, Rai K, Shukla V, Chaturvedi NK, Bociek RG, Pirruccello SJ, Band, H Lu Rand Joshi SS. Sprouty2: A Novel Regulator of BCR and MAPK signaling in CLL Pathogenesis. Blood, First Edition paper, January 25, 2016; DOI 10.1182/blood-2015-09-669317.
  6. Shukla A, Cutucache CG, Sutton GL, Rai K, Rai S, Opavsky R, Swanson PC, Joshi SS. Absence of Caveloin-1 Leads to Delayed Development of Chronic Lymphocytic Leukemia in Eµ-TCL1 Mouse Model. Experimental Hematology 2016, (Published As Cover Story in the January 2016 issue)
  7. Chaturvedi NK, Mir RA, Band V, Joshi SS, Guda C. Experimental validation of predicted subcellular localizations of human proteins. BMC Research Notes 7: 912, 2014.
  8. Mittal AK, Chaturvedi NK, Rai KJ, Gilling-Cutsucache GE, Nordgren TM, Moragues M, Lu R, Opavsky R, Bociek RG, Wesienburger DD, Iqbal J and Joshi SS. Chronic lymphocytic leukemia cells in lymph node microenvironment depict molecular signature associated with an aggressive disease. Molecular Medicine, 20: 290-301, 2014, doi:10.2119/molmed.2012.00303. PMID
  9. Chaturvedi NK, Rajule RN, Shukla A, Radhakrishnan P, Todd GL, Natarajan A, Vose JM, Joshi SS. Novel treatment for mantle cell lymphoma including therapy-resistant tumor by NF-?B and mTOR dual-targeting approach. Mol Cancer Ther. 2013 Oct;12(10):2006-17. doi: 10.1158/1535-7163.MCT-13-0239. Epub 2013 Aug 20. PMID: 23963361
  10. Mittal AK, Chaturvedi NK, Rohlfsen RA, Gupta P, Joshi AD, Hegde GV, Bociek RG, Joshi SS. Role of CTLA4 in the proliferation and survival of chronic lymphocytic leukemia. PLoS One. 2013 Aug 1;8(8):e70352. doi: 10.1371/journal.pone.0070352. Print 2013. PubMed PMID: 23936412; PubMed Central PMCID: PMC3731360.
  11. Shukla A, Chaturvedi NK, Ahrens AK, Cutucache CE, Mittal AK, Bierman P, Weisenburger D, Lu R, Joshi SS. (2013) Stromal Tumor Microenvironment in Chronic Lymphocytic Leukemia: Regulation of Leukemic
  12. Ahrens, AK, Chaturvedi NK, Shukla A, Nordgren TM, Hedge GV, Vose JM, Joshi SS. Polo-Like Kinase 1: A novel Target for the Treatment of Therapy-Resistant Mantle Cell Lymphoma. Lymphoma. Volume: 2013, Article ID 782903, 10 pages.
  13. Christine E. Cutucache, Javeed Iqbal, Philip J. Bierman, Robert Gregory Bociek, Dennis D. Weisenburger, Shantaram S. Joshi, Polycomb response element-binding sites in the MDR of CLL: Potential tumor suppressor regulation. Advances in Bioscience and Biotechnology, 4, 129-135, 2013.
  14. Ahrens AK, Chaturvedi NK, Nordgren TM, Dave BJ, Joshi SS. Establishment and characterization of therapy-resistant mantle cell lymphoma cell lines derived from different tissue sites. Leuk Lymphoma. 2012 Nov;53(11):2269-78. doi:10.3109/ 10428194.2012.691481. Epub 2012 Jun 13. PubMed PMID: 22568512.
  15. Nordgren TM, Hegde GV, Joshi SS (2012) Ritonavir Exhibits Limited Efficacy as a Single Agent in Treating Aggressive Mantle Cell Lymphoma. J Cancer Sci Ther 4: 061-068. doi:10.4172/1948-5956.1000112.
  16. Gilling CE, Mittal AK, Chaturvedi NK, Iqbal J, Aoun P, Bierman PJ, Bociek RG, Weisenburger DD, Joshi SS. Lymph node-induced immune tolerance in chronic lymphocytic leukaemia: a role for caveolin-1. Br J Haematol. 2012 Jul;158(2):216-31. doi: 10.1111/j.1365-2141.2012.09148.x. Epub 2012 May 10. PMID: 22571278.
  17. Munger CM, Hegde GV, Weisenburger DD, Vose JM, Joshi SS. Optimized adoptive T-cell therapy for the treatment of residual mantle cell lymphoma. Cancer Immunol Immunother. 2012 Oct;61(10):1819-32. Epub 2012 Mar 23. PMID: 22441656.
  18. Hegde GV, Nordgren TM, Munger CM, Mittal AK, Bierman PJ, Weisenburger DD, Vose JM, Sharp JG, Joshi SS. Novel therapy for therapy-resistant mantle cell lymphoma: multipronged approach with targeting of hedgehog signaling. Int J Cancer. 2012 Dec 15;131(12):2951-60. doi: 10.1002/ijc.27602. Epub 2012 May 21. PMID: 22511234.
  19. Hlady RA, Novakova S, Opavska J, Klinkebiel D, Peters SL, Bies J, Hannah J, Iqbal J, , Smith LM, Greiner TC, Bastola D, Joshi S, Lockridge O, Simpson MA, Felsher DW, Wagner KU, Chan WC, Christman JK, Opavsky R. Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis. J Clin Invest. 2012 Jan 3;122(1):163-77. doi: 10.1172/JCI57292. Epub 2011 Dec 1. PMID: 22133874
  20. Pathak S, Ma Shibin, Trinh L, Eudy J, Wagner KU, Joshi SS, Lu R. IRF4 is a suppressor of c-myc induced B cell leukemia. PLOS One 6: e22628, 2011.
  21. Kollessery GJ, Nordgren TM, Mittal AK, Joshi SS, Sanderson S. Tumor-Specific Peptide-Based Vaccines Containing the Conformationally Biased, Response-Selective C5a Agonists EP54 and EP67 Protect Against Aggressive Large B Cell Lymphoma in a Syngeneic Murine Model. Vaccine 29: 5904-5910, 2011 .
  22. Trickler WJ, Daniel J. Munt1 DJ, Jain N, Joshi SS, Dash AK, Antitumor Efficacy, Tumor Distribution and Blood Pharmacokinetics of Chitosan/Glycerol-monooleate Nanostructures containing Paclitaxel Compared to a Conventional Paclitaxel Formulation. Nanomedicine 3: 437-448, 2011.
  23. Nordgren TM and Joshi SS. The etiology of chronic lymphocytic leukemia: another look at the relationship between B1 cells and CLL. (Review) The Open Leukemia Journal, 3:69-74, 2010.
  24. Myers-Clark EM, Joshi DS, Wang P, Joshi AD, Grimm AP, Joshi SS. Ultrastructural comparative analyses of dendritic cells derived from cord blood, peripheral blood and bone marrow. International J. Oncology, 37: 645-653, 2010.
  25. Hegde GV, Peterson KJ, Emanuel K, Mittal AK, Joshi AD, Dickson JD, Kollessery GJ, Bociek RG, Bierman PJ, Vose JM, Weisenburger DD, Joshi SS. Hedgehog-induced survival of B-CLL in a stromal cell microenvironment. Molecular Cancer Research 6:1928- 1936, 2008.
  26. Joshi SS, Mittal AK, Joshi AD, Vue E, Xioung W. Differential gene expression in murine large B-cell lymphoma metastatic variants. Int. Immunopharmacology 8:1257-63, 2008.
  27. Hegde GV, Munger CM, Emanuel K, Joshi AD, Weisenburger DD, Vose JM, Joshi SS. Targeting GLI for the treatment of mantle cell lymphoma. Molecular Cancer Therapeutics, 7:1450-60, 2008 (PUBLISHED AS JOURNAL COVER STORY).