MD Anderson Cancer Center in Houston, Texas, is a funny place. It seems that to be employed there one needs to prove an established record of fake research. Maybe they have entire recruitment teams who scan applicants’ papers for forgeries, and trash everyone where they find nothing. Maybe this is also how promotions and contract extensions are decided.

In any case, Professor Kapil Bhalla doesn’t need to worry – he is the perfect fit for MD Anderson, as Sholto David will easily convince you.

Bhalla holds an endowed chair at MD Anderson, his specialty is leading and founding cancer centres: he acted as director of the Cockrell Center at Houston Methodist Research Institute, deputy director of University of Kansas Cancer Center, and founding director of the Medical College of Georgia Cancer Center.

What he obviously can’t do, despite “more than 220 scholarly articles on cancer research“, is western blots.

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Capybara’s Adventures in Medicinal Chemistry

By Sholto David

Every now and again, it is a good idea to open the door of the clown car that is MD Anderson, and see who climbs out. Today is the turn of Kapil N. Bhalla. If you say his name quickly, it sounds a bit like “capybara” but with more syllables. A capybara is a kind of big rat. Kapil N. Bhalla is a Professor in the Leukemia Department of MD Anderson.

I think an informative way to look at Kapil’s work is to start with what is already retracted, and then work through what isn’t yet retracted.

Firstly Kapil was caught up in the mass retraction of papers by Moffit’s Jin Q. Cheng, who lost 19 papers in the Journal of Biological Chemistry (JBC) in 2016, back when they still cared about research integrity. Eight years later, Cheng received his 20th retraction to round up the number, this time in Oncogene.

Kapil was an author on just one of those papers, managing to escape further scrutiny at the time. Another coauthor is Richard Jove, co-founder of Moffitt Cancer Center and former Deputy Director of the NCI Comprehensive Cancer Center. The retraction notice acknowledges duplications and splicing in western blots as the reason for the retraction, some of which I have illustrated below.

Mei Sun, Lin Yang, Richard I. Feldman, Xia-meng Sun, Kapil N. Bhalla, Richard Jove, Santo V. Nicosia, Jin Q. Cheng Activation of phosphatidylinositol 3-kinase/Akt pathway by androgen through interaction of p85alpha, androgen receptor, and Src Journal of Biological Chemistry (2003) doi: 10.1074/jbc.m306295200

Subsequently, a 2012 paper in Cancer Cell accrued PubPeer comments in 2019, and was finally retracted in 2023, this paper was not related to the Jin Q. Cheng scandal. The retraction notice mentions fabrication, falsification, and duplication of western blots in Figures 1B, 5C, 6A, 6G, 7A, and 7B. I’ve included some examples from Figure 7 below.

Xinwei Zhang, Xiaohong Zhao, Warren Fiskus, Jianhong Lin, Tint Lwin, Rekha Rao, Yizhuo Zhang, John C. Chan, Kai Fu, Victor E. Marquez, Selina Chen-Kiang, Lynn C. Moscinski, Edward Seto, William S. Dalton, Kenneth L. Wright, Eduardo Sotomayor, Kapil Bhalla, Jianguo Tao Coordinated silencing of MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in aggressive B-Cell lymphomas Cancer Cell (2012) doi: 10.1016/j.ccr.2012.09.003

The last author Jianguo Tao is pathology professor at the University of Virginia. Also worth mentioning is that the Florida researchers Eduardo Sotomayor (director of a cancer institute at Tampa General Hospital) and Lynn Moscinski ( senior member at Moffit Cancer Center) are, like Kapil, coauthors of Tao on several problematic papers on PubPeer.

So now we have established that fabrication and duplication of western blots are good reasons to retract Kapil N. Bhalla’s papers, how much work is left to do? A lot!

Reign in Blood

Let’s start with papers in Blood, the flagship journal of the American Society of Hematology, under the leadership of Nancy Berliner at Brigand and Women’s Hospital (since 2020 published together with Elsevier). Blood is a safe haven for stupidity in haematology research. Even the worst excesses published by Dana-Farber remain unmolested, see here for example.

The lead author of this first Kapil paper here is no less than Prince George, I was able to obtain a photo of the work being carried out in the lab, I have been assured this photo was not edited in any way.

Prince George, Purva Bali, Srinivas Annavarapu, Anna Scuto, Warren Fiskus, Fei Guo, Celia Sigua, Gautam Sondarva, Lynn Moscinski, Peter Atadja, Kapil Bhalla Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3 Blood (2005) doi: 10.1182/blood-2004-09-3413

In the following paper problems were identified in Figure 2A, Figure 5A, Figure 3D, and Figure 6C. It is all made even funnier by the fact that the penultimate author, the NIH-NCI Scientist Emeritus Victor E. Marquez, whom you already met, not only has other dodgy gels on PubPeer, but he also authored a book, tongue-in-cheek-titled “The Ups and Downs in Drug Design: Adventures in Medicinal Chemistry“:

Warren Fiskus, Yongchao Wang, Arun Sreekumar, Kathleen M. Buckley, Huidong Shi, Anand Jillella, Celalettin Ustun, Rekha Rao, Pravina Fernandez, Jianguang Chen, Ramesh Balusu, Sanjay Koul, Peter Atadja, Victor E. Marquez, Kapil N. Bhalla Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells Blood (2009) doi: 10.1182/blood-2009-03-213496

We have been recently graced with a PubPeer response for the above paper by Kapil himself, you can read the full post here, but for the impatient I will include the most important quote:

“The inadvertent duplication of the cell image in the control panel does not change the conclusion…”

Kapil N. Bhalla

Conclusions not affected. A huge relief I’m sure. There are plenty more forgone conclusions written in Blood.

Warren Fiskus, Rekha Rao, Pravina Fernandez, Bryan Herger, Yonghua Yang, Jianguang Chen, Ravindra Kolhe, Aditya Mandawat, Yongchao Wang, Rajeshree Joshi, Kelly Eaton, Pearl Lee, Peter Atadja, Stephen Peiper, Kapil Bhalla Molecular and biologic characterization and drug sensitivity of pan-histone deacetylase inhibitor-resistant acute myeloid leukemia cells Blood (2008) doi: 10.1182/blood-2007-10-116319

Kapil’s collaborator Stephen Peiper is Senior Vice President of Enterprise Pathology at the Thomas Jefferson University. Like Kapil, Steve is a medical doctor and has no PhD, so maybe they are excused for not knowing how science is supposed to work?

Aditya Mandawat, Warren Fiskus, Kathleen M Buckley, Kelly Robbins, Rekha Rao, Ramesh Balusu, Jean-Marc Navenot, Zi-Xuan Wang, Celalettin Ustun, Daniel G Chong, Peter Atadja, Nobutaka Fujii, Stephen C Peiper, Kapil Bhalla Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and signaling and exerts synergistic antimyeloid activity in combination with CXCR4 antagonists Blood (2010) doi: 10.1182/blood-2010-05-284414

More of Professor Kapil’s attempts at sciencing, with MSKCC bigwig Ross Levine:

Yongchao Wang, Warren Fiskus, Daniel G Chong, Kathleen M Buckley, Kavita Natarajan, Rekha Rao, Atul Joshi, Ramesh Balusu, Sanjay Koul, Jianguang Chen, Andrew Savoie, Celalettin Ustun, Anand P Jillella, Peter Atadja, Ross L Levine, Kapil N Bhalla Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells Blood (2009) doi: 10.1182/blood-2009-05-222133

Here is Kapil with the Rush University professor Celalettin Ustun again:

Ramesh Balusu, Warren Fiskus, Rekha Rao, Daniel G Chong, Srilatha Nalluri, Uma Mudunuru, Hongwei Ma, Lei Chen, Sreedhar Venkannagari, Kyungsoo Ha, Sunil Abhyankar, Casey Williams, Joseph McGuirk, Hanna Jean Khoury, Celalettin Ustun, Kapil N Bhalla Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1 Blood (2011) doi: 10.1182/blood-2010-09-309674

As a final example from Blood (although there are more on PubPeer) here’s a collaboration with James E. Bradner, formerly a senior executive at Novartis and now the chief scientific officer of Amgen.

As I have mentioned previously, he really is caught in the crossfire rather too often, having authored papers with David Sabatini, Ned Sharpless and Bill Hahn, is he just unlucky or something else?

Rekha Rao, Warren Fiskus, Yonghua Yang, Pearl Lee, Rajeshree Joshi, Pravina Fernandez, Aditya Mandawat, Peter Atadja, James E Bradner, Kapil Bhalla HDAC6 inhibition enhances 17-AAG–mediated abrogation of hsp90 chaperone function in human leukemia cells Blood (2008) doi: 10.1182/blood-2008-03-143644

And this isn’t James E. Bradner’s only paper with Kapil, there’s another in JBC where something unfortunate appears to have happened to loading controls from different experiments.

Purva Bali, Michael Pranpat, James Bradner, Maria Balasis, Warren Fiskus, Fei Guo, Kathy Rocha, Sandhya Kumaraswamy, Sandhya Boyapalle, Peter Atadja, Edward Seto, Kapil Bhalla Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors Journal of Biological Chemistry (2005) doi: 10.1074/jbc.c500186200

AACR Joins the Fray

Guess which esteemed society publisher has accepted even more of Kapil’s papers than the American Society of Hematology? It’s the American Association for Cancer Research (AACR) of course! This should come as no surprise as AACR still employs Masimo Loda as an editor in chief. Also worth noting that as of the date of writing AACR have made no apparent effort to correct or retract Sam S. Yoon‘s well documented misdeeds.

The older AACR papers from Kapil Bhalla are full of unlikely looking western blot assemblies, presumably prepared with glue and scissors. Here’s an example where Pinna dolabrata picked out a particular band which must have been copied and pasted (blue rectangles), I’ve added the dashed red rectangles to a neighbouring suspect. Florida legend Richard Jove is again coauthor:

Ramadevi Nimmanapalli, Erica O’Bryan, Mei Huang, Purva Bali, Pearlie Kay Burnette, Thomas Loughran, James Tepperberg, Richard Jove, Kapil Bhalla Molecular characterization and sensitivity of STI-571 (imatinib mesylate, Gleevec)-resistant, Bcr-Abl-positive, human acute leukemia cells to SRC kinase inhibitor PD180970 and 17-allylamino-17-demethoxygeldanamycin Cancer Research (2002) pubmed: 12384536

Here is an impressive finding by the prolific Indigofera tanganyikensis from a paper published in 2014.

Warren Fiskus, Nakhle Saba, Min Shen, Mondana Ghias, Jinyun Liu, Soumyasri Das Gupta, Lata Chauhan, Rekha Rao, Sumedha Gunewardena, Kevin Schorno, Christopher P. Austin, Kami Maddocks, John Byrd, Ari Melnick, Peng Huang, Adrian Wiestner, Kapil N. Bhalla Auranofin induces lethal oxidative and endoplasmic reticulum stress and exerts potent preclinical activity against chronic lymphocytic leukemia Cancer Research (2014) doi: 10.1158/0008-5472.can-13-2033

Kapil’s collaborator, the Weill Cornell professor Ari Melnick was repeatedly mentioned in a story about cheaters from Argentina, because he hosts not one, not two, but three of them as postdocs and assistant professors, all trained in dark magic by Patricia Elizalde.

By 2016 the mirror tool was being deployed by Kapil and Ari, although the obfuscation was not effective here.

Warren Fiskus, Veena Coothankandaswamy, Jianguang Chen, Hongwei Ma, Kyungsoo Ha, Dyana T. Saenz, Stephanie S. Krieger, Christopher P. Mill, Baohua Sun, Peng Huang, Jeffrey S. Mumm, Ari M. Melnick, Kapil N. Bhalla SIRT2 Deacetylates and Inhibits the Peroxidase Activity of Peroxiredoxin-1 to Sensitize Breast Cancer Cells to Oxidant Stress-Inducing Agents Cancer Research (2016) doi: 10.1158/0008-5472.can-16-0126

Moving on to Clinical Cancer Research (AACR is not imaginative when it comes to journal titles, only the research is supposed to be imaginary).

Warren Fiskus, Srdan Verstovsek, Taghi Manshouri, Rekha Rao, Ramesh Balusu, Sreedhar Venkannagari, Nalabothula Narasimha Rao, Kyungsoo Ha, Jacqueline E Smith, Stacey L Hembruff, Sunil Abhyankar, Joseph McGuirk, Kapil N Bhalla Heat shock protein 90 inhibitor is synergistic with JAK2 inhibitor and overcomes resistance to JAK2-TKI in human myeloproliferative neoplasm cells Clinical Cancer Research (2011) doi: 10.1158/1078-0432.ccr-11-1541

Also another AACR journal, Molecular Cancer Therapeutics. With Moffit’s Associate Center Director for Clinical Science Eric Heura, who recently retracted a paper with the sacked JQ Cheng:

Arthur Edwards, Jiannong Li, Peter Atadja, Kapil Bhalla, Eric B. Haura Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor-dependent human lung cancer cells Molecular Cancer Therapeutics (2007) doi: 10.1158/1535-7163.mct-06-0761

Molecular Cancer Therapeutics again; The below two figures might have some kind of logical relationship between some (but not all) of the repeated bands.

Warren Fiskus, Srdan Verstovsek, Taghi Manshouri, Jacqueline E Smith, Karissa Peth, Sunil Abhyankar, Joseph McGuirk, Kapil N Bhalla Dual PI3K/AKT/mTOR inhibitor BEZ235 synergistically enhances the activity of JAK2 inhibitor against cultured and primary human myeloproliferative neoplasm cells Molecular Cancer Therapeutics (2013) doi: 10.1158/1535-7163.mct-12-0862

Springer Nature also accepted at least a couple of problematic figures. Here’s one from Leukemia.

W Fiskus, S Sharma, S Saha, B Shah, S G T Devaraj, B Sun, S Horrigan, C Leveque, Y Zu, S Iyer, K N Bhalla Pre-clinical efficacy of combined therapy with novel β-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells Leukemia (2015) doi: 10.1038/leu.2014.340

And another, from the problem child, Nature Medicine, Ari Melnick is at the helm. This one has now been corrected.

Leandro C Cerchietti, Eloisi C Lopes, Shao Ning Yang, Katerina Hatzi, Karen L Bunting, Lucas A Tsikitas, Alka Mallik, Ana I Robles, Jennifer Walling, Lyuba Varticovski, Rita Shaknovich, Kapil N Bhalla, Gabriela Chiosis, Ari Melnick A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas Nature Medicine (2009) doi: 10.1038/nm.2059 issn: 1546-170x

The astute observers have probably noticed already that another name is very frequently showing up along with Kapil: Warren Fiskus. Fiskus seems to be Kapil’s long-serving assistant, with a biography tracking the same institutions, and he is currently an assistant professor at MD Anderson in the same department. Fiskus mostly authors papers with Kapil, but I did find an interesting collaboration with two familiar names, the brothers dim: Nicholas and Constantine S. Mitsiades.

Costas is at Dana Farber in Boston, and Nikos moved to the opposite end of USA, to University of California Davis.

Bin He, Rainer B. Lanz, Warren Fiskus, Chuandong Geng, Ping Yi, Sean M. Hartig, Kimal Rajapakshe, John Shou, Liping Wei, Shrijal S. Shah, Christopher Foley, Sue Anne Chew, Vijay K. Eedunuri, Diego J. Bedoya, Qin Feng, Takashi Minami, Constantine S. Mitsiades, Anna Frolov, Nancy L. Weigel, Susan G. Hilsenbeck, Daniel G. Rosen, Timothy Palzkill, Michael M. Ittmann, Yongcheng Song, Cristian Coarfa, Bert W. O’Malley, Nicholas Mitsiades GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex PNAS (2014) doi: 10.1073/pnas.1421415111

A quick search for NIH grants to Kapil N. Bhalla shows that he has received over $22 million worth of funding from NIH alone. Meanwhile on PubPeer there are around 40 papers that have been tagged for errors (I have a spreadsheet if anyone is interested). We already know that Kapil and Fiskus are aware of these comments (since they occasionally respond), but so far seem to be uninterested in doing much of anything about the mistakes. It does make one wonder… What exactly was the point of spending so many millions on this research if the authors, journals, universities, and funders don’t seem to care if the final product is riddled with errors?

Note: The name “Kapil N. Bhalla” was whispered in my ear by Clare Francis. Most of the PubPeer findings presented in this post were not identified by me, so credit should be given to the anonymous and pseudonymous commentors, also to Leonid for his help in writing.

Note by LS: Bhalla didn’t reply to my email either.

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