Subbarao Bondada, PhD
ConnectOffice: (859) 323-4705
- Markey Cancer Center
- Diversity Departmental Ambassadors
- Toxicology - Joint Faculty
Biography and Education
B. Sc. (Mathematics, Physics and Chemistry) Andhra Loyola College, Vijayawada, Andhra Pradesh, India M. Sc. (Chemistry) Indian Institute of Technology (IIT), Kanpur, India Ph.D. Tata Institute of Fundamental Research, Mumbai, India
Doctoral Studies: Tata Institute of Fundamental Research, Bombay. Postdoctoral: National Institute of Health, Bethesda, MD and Institute for Cancer Research, Philadelphia, PA.
- 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. In 2019 21000 new CLL cases are expected to be diagnosed, along with 400 deaths due to CLL. It is an incurable disease with an estimated cost of 5.1 billion dollars in medical care costs. We are determining if the tonic BCR signaling is also important for B-CLL using murine and human models. In CLL we are studying the role of the tumor suppressor gene, Par-4 on CLL growth. In addition, we are also investigating the role of CLL-derived IL-10 in cancer immunotherapy.
- Chemobrain is a condition experienced by cancer patients treated with chemotherapy, radiation, and immunotherapy. It consists in variable loss of executive function affecting the quality of life for cancer survivors. We are working with a group of researchers at UKMC, to test the hypothesis that circulating extracellular vesicles carrying oxidized proteins stimulate immune cells to produce cytokines that have neurotoxic effects in cancer patients undergoing or completing their therapies.
- 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.
Selected Recent Publications:
Yarana C, Thompson H, Chaiswing L, Butterfield DA, Weiss H, Bondada S, Alhakeem S, Sukati S, St Clair DK. Extracellular vesicle-mediated macrophage activation: An insight into the mechanism of thioredoxin-mediated immune activation. Redox Biol. 2019 Sep;26:101237. doi: 10.1016/j.redox.2019.101237. Epub 2019 Jun 5. PubMed PMID: 31276937; PubMed Central PMCID: PMC6612011.
Ren X, Boriero D, Chaiswing L, Bondada S, St Clair DK, Butterfield DA. Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment ("chemobrain"), a condition that significantly impairs the quality of life of many cancer survivors. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1088-1097. doi: 10.1016/j.bbadis.2019.02.007. Epub 2019 Feb 10. Review. PubMed PMID: 30759363; PubMed Central PMCID: PMC6502692.
Greene JT, Mani R, Ramaswamy R, Frissora F, Yano M, Zapolnik K, Harrington B, Wasmuth R, Tran M, Mo X, McKenna M, Rangnekar VM, Byrd JC, Bondada S, Muthusamy N. Par-4 overexpression impedes leukemogenesis in the Eµ-TCL1 leukemia model through downregulation of NF-κB signaling. Blood Adv. 2019 Apr 23;3(8):1255-1266. doi: 10.1182/bloodadvances.2018025973. PubMed PMID: 30987970; PubMed Central PMCID: PMC6482354.
Ren X, Keeney JTR, Miriyala S, Noel T, Powell DK, Chaiswing L, Bondada S, St Clair DK, Butterfield DA. The triangle of death of neurons: Oxidative damage, mitochondrial dysfunction, and loss of choline-containing biomolecules in brains of mice treated with doxorubicin. Advanced insights into mechanisms of chemotherapy induced cognitive impairment ("chemobrain") involving TNF-α. Free Radic Biol Med. 2019 Apr;134:1-8. doi: 10.1016/j.freeradbiomed.2018.12.029. Epub 2018 Dec 26. PubMed PMID: 30593843; PubMed Central PMCID: PMC6588453.
Alhakeem SS, McKenna MK, Oben KZ, Noothi SK, Rivas JR, Hildebrandt GC, Fleischman RA, Rangnekar VM, Muthusamy N, Bondada S.
J Immunol. 2018 Jun 15;200(12):4180-4189. doi: 10.4049/jimmunol.1800241. Epub 2018 Apr 30.
McKenna MK, Noothi SK, Alhakeem SS, Oben KZ, Greene JT, Mani R, Perry KL, Collard JP, Rivas JR, Hildebrandt GC, Fleischman RA, Durbin EB, Byrd JC, Wang C, Muthusamy N, Rangnekar VM, Bondada S. Novel role of prostate apoptosis response-4 tumor suppressor in B-cell chronic lymphocytic leukemia. Blood. 2018 Jun 28;131(26):2943-2954. doi: 10.1182/blood-2017-10-813931. Epub 2018 Apr 25. PubMed PMID: 29695515; PubMed Central PMCID: PMC6024641.
Oben KZ, Alhakeem SS, McKenna MK, Brandon JA, Mani R, Noothi SK, Jinpeng L, Akunuru S, Dhar SK, Singh IP, Liang Y, Wang C, Abdel-Latif A, Stills HF Jr, St Clair DK, Geiger H, Muthusamy N, Tohyama K, Gupta RC, Bondada S. Oxidative stress-induced JNK/AP-1 signaling is a major pathway involved in selective apoptosis of myelodysplastic syndrome cells by Withaferin-A. Oncotarget. 2017 Sep 29;8(44):77436-77452. doi: 10.18632/oncotarget.20497. eCollection 2017 Sep 29. PubMed PMID: 29100399; PubMed Central PMCID: PMC5652791. Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice.
Liu Y, Zhang C, Li Z, Wang C, Jia J, Gao T, Hildebrandt G, Zhou D, Bondada S, Ji P, St Clair D, Liu J, Zhan C, Geiger H, Wang S, Liang Y.
Stem Cell Reports. 2017 Apr 11;8(4):991-1004. doi: 10.1016/j.stemcr.2017.02.009. Epub 2017 Mar 16.
PMID:28330618 Free PMC Article
Agrawal AK, Aqil F, Jeyabalan J, Spencer WA, Beck J, Gachuki BW, Alhakeem SS, Oben K, Munagala R, Bondada S, Gupta RC.
Nanomedicine. 2017 Jul;13(5):1627-1636. doi: 10.1016/j.nano.2017.03.001. Epub 2017 Mar 11.
Zhao Y, Carroll DW, You Y, Chaiswing L, Wen R, Batinic-Haberle I, Bondada S, Liang Y, St Clair DK.
Redox Biol. 2017 Aug;12:129-138. doi: 10.1016/j.redox.2017.02.005. Epub 2017 Feb 10.
PMID:28231483Free PMC Article
Select item 280811765.
Oben KZ, Gachuki BW, Alhakeem SS, McKenna MK, Liang Y, St Clair DK, Rangnekar VM, Bondada S.
PLoS One. 2017 Jan 12;12(1):e0169767. doi: 10.1371/journal.pone.0169767. eCollection 2017.
Carroll D, Howard D, Zhu H, Paumi CM, Vore M, Bondada S, Liang Y, Wang C, St Clair DK. Simultaneous quantitation of oxidized and reduced glutathione via LC-MS/MS: An insight into the redox state of hematopoietic stem cells. Free Radic Biol Med. 2016 Aug;97:85-94. doi: 10.1016/j.freeradbiomed.2016.05.005. Epub 2016 May 19. PubMed PMID: 27212018; PubMed Central PMCID: PMC4996720.
Mckenna MK, B. W. Gachuki, S. S. Alhakeem, K. N. Oben, V. M. Rangnekaar, R. C. Gupta, S. Bondada Anti-cancer activity of withaferin A in B-cell lymphoma in Cancer Biol Thera. 2015 May 28:0
Alhakeem SS, Sindhava VJ, McKenna MK, Gachuki BW, Byrd JC, Muthusamy N, Bondada S.
Ann N Y Acad Sci. 2015 Dec;1362:239-249. doi: 10.1111/nyas.12802. Epub 2015 Jun 11.
PMID:26096907Free PMC Article
Gururajan, M. *, V. J. Sindhava* and S. Bondada. B cell tolerance in health and disease in Antibodies. 3, 116-129 (2014)
Tuna H, Avdiushko RG, Sindhava VJ, Wedlund L, Kaetzel CS, Kaplan AM, Bondada S, Cohen DA. Regulation of the mucosal phenotype in dendritic cells by PPARγ: role of tissue microenvironment. J Leukoc Biol. 2014 Mar;95(3):471-85. doi: 10.1189/jlb.0713408. Epub 2013 Dec 2. PubMed PMID: 24295831; PubMed Central PMCID: PMC3923081.
Sindhava, V. * and S. Bondada. Multiple regulatory mechanisms control B-1 B cell activation. Frontiers in Immunology 3: 372 (2012)
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 LymphomasRefaeli 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: ConstitutiveB 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).
Bikah, G. *, J. Carey*, J. Ciallella, A. Tarakhovsky and S. Bondada. CD5 Mediated Negative Regulation of Antigen Receptor-Induced Growth Signals in B-1 B cells. Science 274 (5294): 1906-1909 (1996). PMID: 8943203