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Office: (859) 323-4705
Fax: (859) 257-9608
Lab: (859) 257-5101
Email: bondada@uky.edu
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Subbarao Bondada, Ph.D.
Professor
Doctoral Studies: Tata Institute of Fundamental Research, Bombay.
Postdoctoral: National Institute of Health, Bethesda, MD and Institute for Cancer Research, Philadelphia, PA.
Research Statement:
- Cellular Immunology: Role of dendritic cells in B cell tolerance - Elimination of self-reactive B cells is important to prevent autoimmune disease in the host. This takes place in the bone marrow for most mammals and to some extent in the spleen. Soluble self- protein antigens generally induce anergy while membrane bound self-antigens induce clonal deletion in self-reactive B cells. We found that immature dendritic cells from the bone marrow can present self-antigens to induced clonal deletion in B cells. Present studies are to understand the nature of dendritic cells and the negative signal provided by the dendritic cells to induced clonal deletion of self-reactive B cells.
- B- cell Lymphoma and B-cell chronic lymphocytic leukemia (B-CLL) : Non-Hodgkin’s lymphoma (NHL) is the fifth most common cancer for both males and females in the United States. The age adjusted incidence of non-Hodgkin lymphoma rose by 84% during the period 1975-2004, one of the very few cancers to show an increase in incidence. About 90% NHLs are of B-cell origin, with diffuse large B-cell lymphoma (30-40%) and follicular lymphoma (20%) being the two most common NHLs. Almost 90% of lymphomas are B-cell in origin. We have demonstrated that tonic B cell receptor (BCR) signaling is important for survival of B lymphoma cells and that interfering with BCR signaling at the stage of spleen tyrosine kinase with synthetic small molecules or natural products such as curcumin and withaferin A can inhibit growth of B lymphoma cells. Current efforts are to determine the specific proximal protein tyrosine kinases, especially of the Src family that are important for B lymphoma survival. B-CLL is a leukemia primarily seen in adults. CLL cells are unlike most cancers in that they exhibit very little proliferation but survive for long time in vitro and in vivo. We are determining if the tonic BCR signaling is also important for B-CLL using murine and human models.
- Myeloid Dysplastic Syndrome (MDS) and the role of early growth response -1 (Egr-1): MDS is a disease that appears at late stages of life either as de novo or secondary to treatment of cancer patients with radiation and chemotherapy. The latter group is called therapy related MDS (t-MDS) and is associated with a deletion of small segment of chromosome 5q. This region contains genes for Egr-1 and the micro-RNA, MiR-146 both of which have distinct roles in differentiation of hematopoietic stem cells and progenitor cells. Our goals are to develop animal models to determine the impact of these two genes and other genes present in the 5q deletion on the development of MDS with a long-term goal to identify early biomarkers of the disease and drug targets.
Selected Recent Publications:
Role of phosphoinositide 3-kinase-Akt signaling pathway in the age-related cytokine dysregulation in splenic macrophages stimulated via TLR-2 or TLR-4 receptors.
Fallah MP, Chelvarajan RL, Garvy BA, Bondada S.
Mech Ageing Dev. 2011 Jun-Jul;132(6-7):274-86. doi: 10.1016/j.mad.2011.05.003. Epub 2011 May 27.
PMID:21645538
Systemic Par-4 inhibits non-autochthonous tumor growth.
Zhao Y, Burikhanov R, Brandon J, Qiu S, Shelton BJ, Spear B, Bondada S, Bryson S, Rangnekar VM.
Cancer Biol Ther. 2011 Jul 15;12(2):152-7. Epub 2011 Jul 15.
PMID: 21613819
A shared gene expression signature in mouse models of EBV-associated and non-EBV-associated Burkitt lymphoma.
Bieging KT, Fish K, Bondada S, Longnecker R.
Blood. 2011 Dec 22;118(26):6849-59. doi: 10.1182/blood-2011-02-338434. Epub 2011 Oct 28.
PMID: 22039254
Multifactorial patterns of gene expression in colonic epithelial cells predict disease phenotypes in experimental colitis.
Frantz AL, Bruno ME, Rogier EW, Tuna H, Cohen DA, Bondada S, Chelvarajan RL, Brandon JA, Jennings CD, Kaetzel CS.
Inflamm Bowel Dis. 2012 Nov;18(11):2138-48. doi: 10.1002/ibd.22923. Epub 2012 Feb 22.
PMID: 23070952
Bone marrow dendritic cell-mediated regulation of TLR and B cell receptor signaling in B cells.
Sindhava VJ, Tuna H, Gachuki BW, DiLillo DJ, Avdiushko MG, Onami TM, Tedder TF, Cohen DA, Bondada S.
J Immunol. 2012 Oct 1;189(7):3355-67. Epub 2012 Aug 31.
PMID: 22942427
Latexin is down-regulated in hematopoietic malignancies and restoration of expression inhibits lymphoma growth.
Liu Y, Howard D, Rector K, Swiderski C, Brandon J, Schook L, Mehta J, Bryson JS, Bondada S, Liang Y.
PLoS One. 2012;7(9):e44979. doi: 10.1371/journal.pone.0044979. Epub 2012 Sep 27.
PMID: 23028717
Multiple regulatory mechanisms control B-1 B cell activation.
Sindhava VJ, Bondada S.
Front Immunol. 2012;3:372. doi: 10.3389/fimmu.2012.00372. Epub 2012 Dec 17.
PMID: 23251136 [PubMed]
Sultana, R. , F. Di Domenico, M Tseng, J. Cai , T. Noel , R. L. Chelvarajan, W. D. Pierce, C. Cini , S. Bondada , D. K. St Clair, and D. A. Butterfield. Doxorubicin-Induced Thymus Senescence. J Proteome Res. 2010 Dec 3;9(12):6232-6241. Epub 2010 Nov 9.PMID: 20945937.
Brandon, J., J. Jennings CD, Cohen DA, Sindhava VJ, Bondada S, Kaplan AM, Bryson JS. Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease. Am J Physiol Gastrointest Liver Physiol. 2010 Sep;299(3):G602-13. Epub 2010 Jul 15.PMID: 20634434
Sindhava, V., M. Woodman, B. Stevenson and S. Bondada Interleukin-10 mediated autoregulation of murine B-1 B-cells and its role in Borrelia hermsii infection. PLOS One 2010 Jul 6;5(7):e11445.PMID: 20625435
Ke, J., Chelvarajan, L., Sindhava, V., Lekakis, L., Jennings, D.J. and S. Bondada (2009) Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth. Molec. Cancer Dec 31;8:132-147. PMID: 20043832.
Dasu, T., V. Sindhava, S. G. Clarke and S. Bondada. CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes. Molecular Immunology 46: 2655-2665 (2009).
Wu,H.-S. and S. Bondada CD72, a coreceptor with both positive and negative effects on B lymphocyte development and function. J. Clin. Immunol. 29:12-21 (2009) DOI: 10.1007/s10875-008-9264-6
Gururajan, M., A. Simmons, T. Dasu, B. T. Spear, C. Calulot, D. Robertson, D. Wiest, J. Monroe and S. Bondada. Early growth response gene-1 is required for B cell development, proliferation and immune response. J. Immunol 181(7):4590-602 (2008)
Bondada, S. and M. Gururajan. Importance of B cell receptor signaling for B lymphoma growth.
PLOS Biol. (2008) Comment on The B Cell Antigen Receptor and Overexpression of MYC Can Cooperate in the Genesis of B Cell Lymphomas Refaeli Y, Young RM, Turner BC, Duda J, Field KA, et al. PLoS Biology Vol. 6, No. 6, e152 doi:10.1371/journal.pbio.0060152
Dasu, T., J. E. Qualls, C. Raman, D. A. Cohen and S. Bondada. CD5 plays an inhibitory role in the suppressive function of T-regulatory cells Immunol. Lett. 2008;119(1-2):103-13 .
Yanming Zhao, R. Burikhanov, S. Qiu, S. M. Lele, S. Bondada, B. Spear, and V. M. Rangnekar. Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Res 67:9276-9285 (2007).
Chelvarajan, R. L., D. Popa, Y. Liu, T.V. Getchell, A.J. Stromberg and S. Bondada. Molecular mechanisms underlying anti-inflammatory phenotype of neonatal macrophages. J. Leuk. Bol. 82:403-16. (2007)
Gururajan, M., T. Dasu, S. Shahidain, C. D. Jennings, D. A. Robertson, V. M. Rangnekar and S. Bondada. Curcumin inhibits B lymphoma growth by suppressing Syk, a novel target. J. Immunol. 178: 111-121(2007).
Ke, J., M. Gururajan, A. Kumar, A. Simmons, L. Turcios, Ralph L. Chelvarajan, D. M. Cohen, D. Wiest, J. Monroe and S. Bondada. The role of MAP Kinases in BCR induced down‑regulation of Egr-1 in immature B lymphoma cells. J. Biol. Chem. 281(52):39806-18 (2006).
Landers, C.D. and Subbarao Bondada What insights into human cord blood lymphocyte function can be gleaned from studying newborn mice Questions and Controversies in Neonatology Series, Hematology, Immunology, and Infectious Diseases Volume; Editors: Robin Ohls, and Mervin C. Yoder, (2006).
Gururajan, M., C. D. Jennings, and S. Bondada. Cutting Edge: Constitutive B cell receptor signaling is critical for basal growth of B lymphoma. J. Immunol. 176: 5715-5719 (2006).
S. Bondada and H-S. Wu Molecule Page, A000582, CD72, AfCS-Nature Molecule Pages (2006) (peer reviewed like any journal manuscript).
Chelvarajan, R. L., Y. Liu, D. Popa, M.L. Getchell, T.V. Getchell, A.J. Stromberg and S. Bondada. Molecular basis of age associated cytokine dysregulation in macrophages. J. Leuk. Bol. 79: 1314-1327 (2006).
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