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: ssjoshi@unmc.edu

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, cell cycle/division and cancer biology.

Core/Course Directorship:

  • Co-Core Director for Medical Cellular Processes Core
  • Laboratory Director for Cellular Processes Core
  • Co-Course Director for Graduate Course BRTP 822 (Molecular Cell Biology)
  • Course Director for Graduate Course GCBA 806 (Development of Teaching and Research Presentation Skills)

Research Activities/Interests:

Overall goals: The long-term goal of this laboratory is to improve therapy for human B lymphocytic malignancies by means of translational research involving molecular characterization of malignant B cells.

Tumor Microenvironment in chronic lymphocytic leukemia (CLL). CLL is the most common leukemia of the older population in Western countries. Resistance to therapy due to 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 bcl-2 or Cyclin-D3) became significantly more susceptible to 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. DCs are the most potent antigen-presenting cells which exhibit significant immunostimulatory properties. These immunostimulatory properties of DCs make them a potential source for improving immune-based therapy against cancer. 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. DCs generated from mononuclear cells from MCL patients are fused with autologous lymphoma cells. Such DCs primed with MCL antigens will then be used for the generation of CTLs against MCL. At present, these studies have been performed using NOD-SCID mice bearing human mMCL cells. We are in the process of taking this approach to the clinic with additional molecular studies to characterize therapy-resistant MCL.

Publications listed in PubMed

Recent Publications:

Publications from the last Five Years

  1. 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 leukemia: 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. PubMed PMID: 22571278.
  2. 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 Mar 23. [Epub ahead of print] PubMed PMID: 22441656.
  3. 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 Apr 17. doi: 10.1002/ijc.27602. [Epub ahead of print] PubMed PMID: 22511234.
  4. Nordgren TM, Hegde GV and Joshi SS. Limited Utility of the FDA-approved protease inhibitor ritonavir in treating aggressive mantle cell lymphoma. J. Cancer Science and Therapy, EPub 2012.
  5. 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 Jun 13. [Epub ahead of print] PubMed PMID: 22568512.
  6. Pathak S, Ma S, Trinh L, Eudy J, Wagner KU, Joshi SS, Lu R. IRF4 is a suppressor of c-Myc induced B cell leukemia. PLoS One. 2011;6(7):e22628. Epub 2011 Jul 27. PubMed PMID: 21818355; PubMed Central PMCID: PMC3144921.
  7. Nordgren TM and Joshi SS. The etiology of chronic lymphocytic leukemia: Another look at the relationship between B1 cells and CLL. The Open Leukemia Journal, 3: 69-73, 2010.
  8. Hegde GV, Munger CM, Emanuel K, Joshi AD, Greiner TC, Weisenburger DD, Vose JM, Joshi SS. Targeting of sonic hedgehog-GLI signaling: a potential strategy to improve therapy for mantle cell lymphoma. Mol Cancer Ther. 2008 Jun;7(6):1450-60. Epub 2008 Jun 4. PubMed PMID: 18524848. (COVER STORY)
  9. Hegde GV, Peterson KJ, Emanuel K, Mittal AK, Joshi AD, Dickinson JD, Kollessery GJ, Bociek RG, Bierman P, Vose JM, Weisenburger DD, Joshi SS. Hedgehog-induced survival of B-cell chronic lymphocytic leukemia cells in a stromal cell microenvironment: a potential new therapeutic target. Mol Cancer Res. 2008 Dec;6(12):1928-36. PubMed PMID: 19074837.
  10. Joshi AD, Hegde GV, Dickinson JD, Mittal AK, Lynch JC, Eudy JD, Armitage JO, Bierman PJ, Bociek RG, Devetten MP, Vose JM, Joshi SS. ATM, CTLA4, MNDA, and HEM 1in high versus low CD38 expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5295-304. PubMed PMID: 17875758. (COVER CITATION)
  11. Joshi AD, Dickinson JD, Hegde GV, Sanger WG, Armitage JO, Bierman PJ, Bociek RG, Devetten MP, Vose JM, Joshi SS. Bulky lymphadenopathy with poor clinical outcome is associated with ATM downregulation in B-cell chronic lymphocytic leukemia patients irrespective of 11q23 deletion. Cancer Genet Cytogenet. 2007 Jan 15;172(2):120-6. PubMed PMID: 17213020.
  12. Hlady RA, Novakova S, Opavska J, Klinkebiel D, Peters SL, Bies J, Hannah J, Iqbal J, Anderson KM, Siebler HM, Smith LM, Greiner TC, Bastola D, Joshi SS, 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. PubMed PMID: 22133874; PubMed Central PMCID: PMC3248285. 
  13. 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.
  14. 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.
  15. Hegde GV, Munger CM, Emanuel K, Joshi AD, Weisenburger DD, Vose JM, Joshi SS. Targeting GLI for the treatment of mantle cell lymphoma. Mol. Cancer Therapeutics, 7:1450-60, 2008 (cover story).
  16. Hegde GV, Clark DM, Joshi SS, Sanderson S. A conformationally-biased, response-selective agonist of C5a acts as a molecular adjuvant by modulating antigen processing and presentation activities of human dendritic cells. Int. Immunopharmacology, 8:819-827, 2008.
  17. Iqbal J, Joshi SS, Patel K, Javed S, Kucuk C, Aabida A, dAmore F, Fu K. clinical implication of genome-wide profiling in diffuse large B-cell lymphoma (review) Indian J. Cancer 44:72-86, 2007.
  18. Joshi, AD, Dickinson JD, Ganapati V. Hegde, GV, Sanger WG, James O. Armitage JO, Bierman PJ, Bociek RG, Devetten MP, Julie M. Vose JM, Joshi SS.  Bulky Lymphadenopathy with Poor Clinical Outcome is Associated with ATMDown Regulation in B-CLL Patients Irrespective of 11q23 Deletion, Cancer Genetics, and Cytogenetics, 172: 120-126, 2007.
  19. Joshi AD, Wang P, Munger CM, Joshi SS, Cellular immunotherapy for human neuroblastoma using umbilical cord blood derived effector cells. J. Neuroimmune Pharmacology, 2: 202-212, 2007.
  20. Reddy MK, Vasir JK, Hegde GV, Joshi SS, Labhasetwar V. Erythropoietin induces excessive neointima formation: A study in a rat carotid artery model of vascular injury. J. Cardiovascular Pharmacology and Therapeutics 12: 237-247, 2007.
  21. Mittal AK, Hegde GV, Aoun P, Bociek RG, Dave BJ, Joshi AD, Weisenburger DD, Joshi SS. Molecular basis of aggressive disease in chronic lymphocytic leukemia patients with 11q deletion and trisomy 12 chromosomal abnormalities. Int. J. Molecular Medicine 20: 461-469, 2007.
  22. Joshi AD, Hedge GV, Dickinson JD, Mittal AK, Lynch JC, Eudy JD, Armitage JO, Bierman, PH, Bociek RG, Devetten MP, Vose JM and Joshi SS. ATM, CTLA4, MNDA and HEM1 in high versus low CD38-expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res 13:(18) 5895-5304, 2007.

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