Bharat Aggarwal

Bharat B. Aggarwal is an Indian-American biochemist. His research has been in the areas of cytokines, the role of inflammation in cancer, and the anti-cancer effects of spices and herbs, particularly curcumin (a chemical constituent of the spice turmeric). He was a professor in the Department of Clinical Immunology, Bioimmunotherapy, and Experimental Therapeutics at University of Texas MD Anderson Cancer Center in Houston, Texas.[1]

Bharat B. Aggarwal
Alma materUniversity of Delhi
Banares Hindu University
University of California, Berkeley
Scientific career
FieldsBiochemistry
InstitutionsMD Anderson Cancer Center
Genentech

In 2012, MD Anderson launched a review of Aggarwal's research after the federal government notified them of allegations of fraud by academic whistleblowers in as many as 65 of Aggarwal's published papers, with the allegations involving images that had been reused and manipulated to represent different results.[2][3][4] He retired at the end of 2015; his departure was not made public until February 2016.[1][5]

As of 2020, 29 papers published by Aggarwal have been retracted, ten others have received an expression of concern, and 17 others have been corrected.[6][7]

Career

Aggarwal holds a Bachelor of Science degree from the University of Delhi (1970), a Master of Science degree from Banares Hindu University (1972) and a Doctor of Philosophy degree from the University of California, Berkeley (1977), all in biochemistry. He completed a postdoctoral fellowship at the University of California, San Francisco and was employed as a scientist at Genentech from 1980 to 1989, where his team characterized the cytokines TNF-alpha and TNF-beta. Aggarwal was Chief of the Cytokine Research Section, Department of Clinical Immunology, Bioimmunotherapy, Experimental Therapeutics at MD Anderson Cancer Center of the University of Texas in Houston from 1989 to 2015.[8][9]

Aggarwal's research has focused on potential anti-cancer properties of herbs and spices, particularly curcumin, which is found in the spice turmeric.[8][10] In 2004 Aggarwal co-founded the company Curry Pharmaceuticals, based in Research Triangle Park, N.C., which was seeking to develop drugs based on synthetic analogs of curcumin.[8][11] SignPath Pharma, a company seeking to develop liposomal formulations of curcumin, in 2013 licensed three patents from Aggarwal related to that approach.[12]

Scientific misconduct

In 2012, MD Anderson initiated a review of Aggarwal's research after the U.S. Department of Health and Human Services' Office of Research Integrity notified the institution that academic whistleblowers had found evidence of image manipulation in 65 published papers by Aggarwal.[2][13]

Aggarwal's lawyer proposed in 2013 legal action against the blog Retraction Watch after they reported several of Aggarwal's article corrections and retractions;[14] no such lawsuit was ever realized. In February 2016, the journal Biochemical Pharmacology retracted seven of Aggarwal's research articles, six of which had Aggarwal as senior or first author,[4] because "the data integrity has become questionable."[3] Also in February 2016, MD Anderson Cancer Center confirmed that Aggarwal had retired from the Center on December 31, 2015.[5][1]

In June 2016, following an investigation by MD Anderson Cancer Center, the journal Molecular Pharmacology retracted two of Aggarwal's papers, citing “inappropriate” or “unacceptable” image manipulation.[15] By April 2018, 19 of Aggarwal's articles, published in 7 research journals, had been retracted.[16][3][17][1] In September 2018, an additional nine articles by Aggarwal were retracted in journals published by the American Association for Cancer Research.[18]

In February 2018, a cancer conference in Chennai, India co-organized by Aggarwal was promoted with the false claim that it was co-sponsored by MD Anderson Cancer Center.[19][20][21]

Retracted articles

As of  2020, 29 of Aggarwal's research papers have been retracted, including:

  1. Aggarwal, BB; et al. (1 April 2007). "Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines". Biochemical Pharmacology. 73 (7): 1024–32. doi:10.1016/j.bcp.2006.12.010. PMID 17240359. (Retracted, see doi:10.1016/j.bcp.2015.11.012, PMID 26985469)
  2. Tharakan, ST; et al. (15 January 2010). "Curcumin potentiates the antitumor effects of gemcitabine in an orthotopic model of human bladder cancer through suppression of proliferative and angiogenic biomarkers". Biochemical Pharmacology. 79 (2): 218–28. doi:10.1016/j.bcp.2009.08.007. PMC 3181149. PMID 19682434. (Retracted, see doi:10.1016/j.bcp.2015.11.010, PMC 4801035, PMID 26985467)
  3. Anand, P; et al. (1 February 2010). "Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo". Biochemical Pharmacology. 79 (3): 330–8. doi:10.1016/j.bcp.2009.09.003. PMC 3181156. PMID 19735646. (Retracted, see doi:10.1016/j.bcp.2015.11.008, PMC 4809038, PMID 26985465)
  4. Ravindran, J; et al. (1 June 2010). "Thymoquinone poly (lactide-co-glycolide) nanoparticles exhibit enhanced anti-proliferative, anti-inflammatory, and chemosensitization potential". Biochemical Pharmacology. 79 (11): 1640–7. doi:10.1016/j.bcp.2010.01.023. PMC 2846982. PMID 20105430. (Retracted, see doi:10.1016/j.bcp.2015.11.011, PMC 4809052, PMID 26985468)
  5. Yadav, VR; et al. (1 October 2010). "Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake". Biochemical Pharmacology. 80 (7): 1021–32. doi:10.1016/j.bcp.2010.06.022. PMC 2923254. PMID 20599780. (Retracted, see doi:10.1016/j.bcp.2015.11.007, PMC 4801114, PMID 26985464)
  6. Park, B; et al. (1 November 2011). "Triptolide, histone acetyltransferase inhibitor, suppresses growth and chemosensitizes leukemic cells through inhibition of gene expression regulated by TNF-TNFR1-TRADD-TRAF2-NIK-TAK1-IKK pathway". Biochemical Pharmacology. 82 (9): 1134–44. doi:10.1016/j.bcp.2011.07.062. PMC 3191321. PMID 21820422. (Retracted, see doi:10.1016/j.bcp.2015.11.006, PMC 4801115, PMID 26985463)
  7. Anand, P; et al. (15 December 2011). "Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors". Biochemical Pharmacology. 82 (12): 1901–9. doi:10.1016/j.bcp.2011.09.001. PMC 3216474. PMID 21924245. (Retracted, see doi:10.1016/j.bcp.2015.11.009, PMC 4801119, PMID 26985466)
  8. Anand, P; et al. (15 December 2011). "Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors". Biochemical Pharmacology. 82 (12): 1901–9. doi:10.1016/j.bcp.2011.09.001. PMC 3216474. PMID 21924245. (Retracted, see doi:10.1016/j.bcp.2015.11.009, PMC 4801119, PMID 26985466)
  9. Yadav, VR; et al. (17 December 2011). "WITHDRAWN: Cardamonin Inhibits Osteoclastogenesis Induced by Tumor Cells Through Interruption of the Signaling Pathway Activated by Receptor Activator of NF-κB Ligand". Cancer Letters. doi:10.1016/j.canlet.2011.12.011. PMC 3769506. PMID 22182452.
  10. Sung, B; et al. (9 April 2010). "Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and up-regulation of death receptors". The Journal of Biological Chemistry. 285 (15): 11498–507. doi:10.1074/jbc.M109.090209. PMC 2857028. PMID 20154087. (Retracted, see doi:10.1074/jbc.A109.090209, PMC 4974403, PMID 27496961)
  11. Prasad, S; et al. (27 August 2010). "Crotepoxide chemosensitizes tumor cells through inhibition of expression of proliferation, invasion, and angiogenic proteins linked to proinflammatory pathway". The Journal of Biological Chemistry. 285 (35): 26987–97. doi:10.1074/jbc.M110.121061. PMC 2930698. PMID 20576605. (Retracted, see doi:10.1074/jbc.A110.121061, PMC 4974404, PMID 27496962)
  12. Sung, B; et al. (12 November 2010). "Gossypol induces death receptor-5 through activation of the ROS-ERK-CHOP pathway and sensitizes colon cancer cells to TRAIL". The Journal of Biological Chemistry. 285 (46): 35418–27. doi:10.1074/jbc.M110.172767. PMC 2975165. PMID 20837473. (Retracted, see doi:10.1074/jbc.A110.172767, PMC 4974406, PMID 27496964)
  13. Kannappan, R; et al. (22 October 2010). "γ-Tocotrienol but not γ-tocopherol blocks STAT3 cell signaling pathway through induction of protein-tyrosine phosphatase SHP-1 and sensitizes tumor cells to chemotherapeutic agents". The Journal of Biological Chemistry. 285 (43): 33520–8. doi:10.1074/jbc.M110.158378. PMC 2963373. PMID 20720018. (Retracted, see doi:10.1074/jbc.A110.158378, PMC 4974405, PMID 27496963)
  14. Gupta, SC; et al. (14 January 2011). "Nimbolide sensitizes human colon cancer cells to TRAIL through reactive oxygen species- and ERK-dependent up-regulation of death receptors, p53, and Bax". The Journal of Biological Chemistry. 286 (2): 1134–46. doi:10.1074/jbc.M110.191379. PMC 3020720. PMID 21078664. (Retracted, see doi:10.1074/jbc.A110.191379, PMC 4974408, PMID 27496966)
  15. Prasad, S; et al. (18 February 2011). "Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors: evidence for the role of reactive oxygen species and JNK". The Journal of Biological Chemistry. 286 (7): 5546–57. doi:10.1074/jbc.M110.183699. PMC 3037668. PMID 21156789. (Retracted, see doi:10.1074/jbc.A110.183699, PMC 4974407, PMID 27496965)
  16. Yadav, VR; et al. (2 January 2012). "3-Formylchromone interacts with cysteine 38 in p65 protein and with cysteine 179 in IκBα kinase, leading to down-regulation of nuclear factor-κB (NF-κB)-regulated gene products and sensitization of tumor cells". The Journal of Biological Chemistry. 287 (1): 245–56. doi:10.1074/jbc.M111.274613. PMC 3249075. PMID 22065587. (Retracted, see doi:10.1074/jbc.A111.274613, PMC 4974409, PMID 27496967)
  17. Takada, Y; et al. (May 2008). "Flavopiridol suppresses tumor necrosis factor-induced activation of activator protein-1, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), p44/p42 MAPK, and Akt, inhibits expression of antiapoptotic gene products, and enhances apoptosis through cytochrome c release and caspase activation in human myeloid cells". Molecular Pharmacology. 73 (5): 1549–57. doi:10.1124/mol.107.041350. PMID 18287248. (Retracted, see doi:10.1124/mol.115.041350retraction, PMC 4931863, PMID 27301881)
  18. Phromnoi, K; et al. (February 2011). "A novel pentamethoxyflavone down-regulates tumor cell survival and proliferative and angiogenic gene products through inhibition of IκB kinase activation and sensitizes tumor cells to apoptosis by cytokines and chemotherapeutic agents". Molecular Pharmacology. 79 (2): 279–89. doi:10.1124/mol.110.067512. PMC 3033709. PMID 20930110. (Retracted, see doi:10.1124/mol.115.067512retraction, PMC 4931867, PMID 27301882)
  19. Prasad, S; et al. (2017). "Curcumin-Free Turmeric Exhibits Activity against Human HCT-116 Colon Tumor Xenograft: Comparison with Curcumin and Whole Turmeric". Frontiers in Pharmacology. 8: 871. doi:10.3389/fphar.2017.00871. PMC 5732987. PMID 29311914. (Retracted, see doi:10.3389/fphar.2018.00400, PMC 5912071, PMID 29697698)

Books

See also

References
  1. Ackerman, Todd (March 4, 2016). "M.D. Anderson scientist, accused of manipulating data, retires". Houston Chronicle. Archived from the original on October 10, 2016. Retrieved October 6, 2016.
  2. Ackerman, Todd (February 24, 2012). "M.D. Anderson professor under fraud probe". Houston Chronicle. Retrieved March 24, 2015.
  3. Grens, Kerry (February 22, 2016). "Author Nets Seven Retractions". The Scientist. Retrieved October 6, 2016.
  4. Nybo, Kristie (February 24, 2016). "Seven Papers Retracted for Lack of Data Integrity". BioTechniques. Archived from the original on October 12, 2016. Retrieved October 11, 2016.
  5. Oransky, Ivan (2016-02-22). "Journal retracts 7 papers by MD Anderson cancer researcher long under investigation". Retraction Watch. Retrieved 2016-02-24.
  6. "Cancer journals retract 10 papers, flag 8 more, and apologize for the delay". Retraction Watch. 2018-09-04. Retrieved 2018-09-04.
  7. "Retraction Watch Database – Bharat Aggarwal". Retraction Watch. Center for Scientific Integrity. Retrieved 2020-09-21.
  8. Stix, Gary (February 2007). "Spice Healer". Scientific American. 296 (2): 66–9. Bibcode:2007SciAm.296b..66S. doi:10.1038/scientificamerican0207-66. PMID 17367023.
  9. Gazella, Karolyn A. (December 2009). "Pioneering Biochemist Bharat B. Aggarwal, PhD, of the M.D. Anderson Cancer Center, on Discovering Novel and Effective Cancer Treatments". Natural Medicine Journal. Retrieved March 25, 2015.
  10. Ackerman, Todd (July 11, 2005). "In cancer fight, a spice brings hope to the table". Houston Chronicle. Retrieved March 24, 2015.
  11. Singh, Seema (September 7, 2007). "From Exotic Spice to Modern Drug?". Cell. 130 (5): 765–768. doi:10.1016/j.cell.2007.08.024. PMID 17803897. S2CID 16044143.
  12. Baum, Stephanie (March 26, 2013). "Biotech startup raises $1M for lung cancer treatment using component of tumeric [sic]". Med City News.
  13. "Prominent Indian-American researcher under probe". Deccan Herald. February 25, 2012. Retrieved October 10, 2016.
  14. Heisel, William (April 19, 2013). "Doctor Goes After Retraction Watch, Unleashes Streisand Effect". USC Annenberg School for Communication and Journalism – Center for Health Journalism. Retrieved October 6, 2016.
  15. Lewis, Tanya (June 22, 2016). "More Retractions for Cancer Researcher". The Scientist. Retrieved October 10, 2016.
  16. "Caught Our Notice: Researcher who once threatened to sue Retraction Watch now up to 19 retractions". Retraction Watch. 10 April 2018.
  17. "Seven retractions for prominent cancer researcher brings total to 18". Retraction Watch. Retrieved October 6, 2016.
  18. "Publisher's Note". Cancer Research. AACR Publications. 78 (17): 5178. 2018. doi:10.1158/0008-5472.CAN-18-2438. Retrieved 4 September 2018.
  19. Oransky, Ivan (February 5, 2018). "MD Anderson: No, we did not co-sponsor this cancer conference". Retraction Watch. Retrieved January 9, 2019.
  20. Unni, Anagha (February 4, 2018). "After 'cancer is karma' remark, Baba Ramdev to inaugurate research conference at IIT Madras". Indian Express. Retrieved January 9, 2019.
  21. Chu, Will (April 13, 2018). "Curcumin trial retraction latest in long line for retired researcher". NutraIngredients. Retrieved January 9, 2019.
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