Genetics, Cell Biology & Anatomy

Professor

University of Bombay, India
1979 

Phone: (402) 559-4165
Fax:    (402) 559-3400
Email:  ssjoshi@unmc.edu
www.unmc.edu/genetics

Teaching Activities:

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

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.

Functional genomics for improved therapy for chronic lymphocytic leukemia (CLL).  CLL is a 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. Using DNA microarray analysis, the differentially-expressed genes in therapy-resistant CLL cells from patients or from patients with poor prognosis are being identified. 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.

Dendritic cell-based therapy for Mantle Cell Lymphoma (MCL). Mantle cell lymphoma is a 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, an immune-based therapy, such as DC-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 dendritic cell immonotherapy against MCL. At present, these studies are being performed using NOD-SCID mice bearing human mMCL cells. Initial results are very promising in eliminating residual MCL cells.

Publications listed in PubMed

Recent Publications:

Publications from the last Three Years

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. 

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.

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).

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.

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.

Dickinson JD, Smith LM, Sanger WG, Zhou G, Townley P, Lynch JC, Pavletic ZS, Bierman PJ,  Joshi SS. Unique gene expression and clinical characteristics are associated with the 11q23 deletion in chronic lymphocytic leukemia British J. Haematology 128: 460-471, 2005.

Dickinson JD,  Gilmore J, Iqbal J, Sanger WG, Lynch JC, Chan WC, Bierman PJ, Joshi SS. 11q22.3 deletion in B-chronic lymphocytic leukemia is specifically associated with

bulky lymphadenopathy and ZAP-70 expression but not reduced expression of adhesion/cell surface receptor molecules. Leukemia Lymphoma 47: 231-244, 2006.

Dickinson JD, Joshi AD, Iqbal J, Sanger WG, Bierman PJ, Joshi SS. Genomic abnormalities in chronic lymphocytic leukemia influence gene expression by a dosage effect. International J. Molecular Medicine, 17: 769-778, 2006.

Munger CM, Vose JM and Joshi SS.  Optimizing dendritic cell based therapy for human mantle cell lymphoma. International J. Oncology, 28, 1337-1343, 2006.

Chakravarthi  D,  Zeed M, Bbackora M,  Myers EM, Weisenburger DD, Cavalieri EL, Rogan EG, Joshi SS. Quinones of benzene and estrogen induce hyperproliferation of human peripheral blood mononuclear cells.   Leukemia and Lymphoma. 47: 2635-2644, 2006.

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 ATM Down Regulation in B-CLL Patients Irrespective of 11q23 Deletion, Cancer Genetics, and Cytogenetics, 172: 120-126, 2007.

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.

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.

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 lversus low CD38-expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res 13:(18) 5895-5304, 2007.