Department of Genetics, Cell Biology and Anatomy
PhD, University of Bombay, India, 1979
Block Director, COM Blood, Defenses and Invaders Block
Advisor, Masters in Medical Anatomy
Co-Course Director, IPBS 802: Molecular Cell Biology
Co-Course Director, MGCB 907: Teaching and Research Presentation Skills
Co-Course Director, GCBA 825: Human Histology
Course Director, GCBA 971: Professional Opportunities Seminar
Honors & Awards:
Inspirational Mentor of Educators Award, UNMC, 2017
Outstanding Teaching Award, UNMC, 2011
College of Medicine Class of 1962 Basic Science Outstanding Teacher Award, UNMC, 2005
Dr. Joshi is involved in teaching both medical and graduate students. For medical students, he teaches cell and molecular biology, histology including hematopoiesis & immunology, and problem-based learning. For graduate students, he teaches cell biology, molecular cell biology, cell cycle/division, and cancer biology.
As an educator of professional and graduate students, Dr. Joshi believes that he must provide the main concepts, appropriate levels of content, and credible main resources. To promote active learning, he uses self-paced and self-directed tools like e-Modules, team-based, case-based and/or problem-based learning.
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 the rest of Western countries. Resistance to therapy due to CLL cell –favorable alterations in apoptosis and cell cycle regulation is a major problem in the clinical management of CLL. Therefore, improvements in existing therapy and/or new effective therapies are essential. Emerging evidence suggests 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 the 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 D1 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 pediatric cancer patients in Nebraska, with the funds from the State of Nebraska, UNMC has initiated the 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 the molecular basis of this process, we expect to identify viable therapeutic targets to improve therapy from EWS.
- Kling MJ, Connor NG, McIntyre EM, Alexander G, Ray S, Challagundla KB, Joshi SS; Coulter DW, Chaturvedi NK. Synergistic efficacy of inhibiting MYCN and mTOR signaling against neuroblastoma. BMC cancer. 21: 2022.
- Kling MJ, Chaturvedi NK, Kesherwani V, Coulter DW, McGuire TR, J. Sharp JG, Joshi SS. Exosomes secreted under hypoxia enhance stemness in Ewing's sarcoma through miR-210 delivery. Oncotarget. 11: 3633-3645. 2020 (PUBLISHED AS COVER STORY).
- Shukla A, Shukla V, Joshi SS. Regulation of MAPK signaling and implications in chronic lymphocytic leukemia. Leuk. Lymphoma. 59 : 1565-1573. 2018 (Invited Review).
- Shukla A, Rai K, Shukla V, Chaturvedi NK, Bociek RG, Pirruccello SJ, Band H, Lu R, Joshi SS. Sprouty 2: A novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL. Blood. 127 : 2310-2321. 2016.
- Shukla V, Shukla A, Joshi SS, Lu R. Interferon regulatory factor 4 attenuates Notch signaling to suppress the development of chronic lymphocytic leukemia. Oncotarget. 7 : 41081-41094. 2016.
- Shukla A, Cutucache CE, Sutton GL, Pitner MA, Rai K, Rai S, Opavsky R, Swanson PC, Joshi SS. Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model. Experimental Hematology. 44: 30-37. 2016.
- Mittal AK, Chaturvedi NK, Rai KJ, Gilling-Cutucache CE, Nordgren TM, Moragues M, Lu R, Opavsky R, Bociek GR, Weisenburger DD, Iqbal J, Joshi SS. Chronic lymphocytic leukemia cells in a lymph node microenvironment depict molecular signature associated with an aggressive disease. Molecular Medicine. 20: 290-301. 2014.
- 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-κB and mTOR dual-targeting approach. Mol3cular Cancer Therapeutics.12: 2006-2017. 2013.
- Shukla V, Ma S, Hardy RR, Joshi SS, Lu R. A role for IRF4 in the development of CLL. Blood. 122: 2848-2855. 2013.
- 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. International Journal of Cancer. 131: 2951-2960. 2012.
- Munger CM, Hegde GV, Weisenburger DD, Vose JM, Joshi SS. Optimized adoptive T-cell therapy for the treatment of residual mantle cell lymphoma. Cancer Immunology, Immunotherapy. 61: 1819-1832. 2012.
- 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. British Journal of Haematology. 158 : 216-231. 2012.
- 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. Molecular Cancer Research. 6: 1928-1936. 2008 (PUBLISHED AS COVER STORY).
- 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 Genetics and Cytogenetics. 172 : 120-126. 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 leukaemia. British Journal of Haematology. 128: 460-471. 2005.