Research integrity University Affairs

The Hupp and Ball Game

"Ted Hupp and Kathryn Ball may very well feel like kissing David Argyle on both cheeks."

Clare Francis said:

“Ted Hupp and Kathryn Ball may very well feel like kissing David Argyle on both cheeks.”

That’s because when the pseudonymous image integrity sleuth heard of David Argyle’s bullying and the cover-up by the University of Edinburgh in Scotland, UK, Clare Francis started to screen Argyle’s papers for image irregularities. And soon stumbled over Argyle’s postdoc Lisa Pang, who did her PhD at the Cancer Research UK (CRUK) Edinburg Centre and MRC Institute of Genetics & Molecular Medicine under Ted Hupp, the US-born Edinburgh professor, who proved to be Argyle’s collaborator.

Right away, Clare Francis found a treasure trove of questionable research papers from Hupp’s lab. From Hupp’s papers, the sleuth stumbled upon another Edinburgh professor, Kathryn Ball, and her lab’s papers proved a treasure trove as well!

Hupp and Ball are in fact a husband-and-wife team, they both started together as PhD students at the Michigan State University in USA, moved together as postdocs to Scotland, both to the University of Dundee lab of Sir David Lane (who is now at Karolinska Institutet in Stockholm, Sweden, and not replying to emails). Hupp and Ball then both became professors at the same Institute of Genetics and Cancer by CRUK and MRC in Edinburgh. Both work on cell cycle regulation, he on p53, she on the p21 protein. Both sit on the scientific advisory board of the Scottish biotech startup ILC Therapeutics which seeks to cure with interferon drugs various diseases including COVID-19. Both published, together and separately, Photoshopped stuff they should be deeply ashamed for, and both remained silent when I contacted them.

I want to celebrate this power couple.

Here is how Clare Francis was led to playing the Hupp and Ball game. From Argyle to Pang to Hupp to Ball.

Lisa Y. Pang, Mary Scott , Richard L. Hayward , Hisham Mohammed , C. Bruce A. Whitelaw, Graeme C.M. Smith , Ted R. Hupp p21(WAF1) is component of a positive feedback loop that maintains the p53 transcriptional program Cell Cycle (2011) doi: 10.4161/cc.10.6.15012

A Ponseau S blot image, “accidentally” reused, once in colour, once black-and-white, for two unrelated experiments. Why couldn’t the correct loading control be used? A mystery.

Here a paper by Hupp and Ball, rather old, raw data unavailable, but even Hupp agrees the gel is falsified:

Ashley Craig , Mary Scott , Lindsay Burch , Graeme Smith , Kathryn Ball, Ted Hupp Allosteric effects mediate CHK2 phosphorylation of the p53 transactivation domain EMBO reports (2003) doi: 10.1038/sj.embor.embor901

Hupp declared on PubPeer in June 2021:

The authors think that the apparent similarity resulted from image crop/paste from different gels to condense key data from Fig 1d of the same paper, but the original data are no longer available for analysis. This particular image does not affect the overall data interpretation or the conclusions from the study; regarding stimulation of the chk2 kinase using synthetic peptides (named 5 and 18) that are the best binders to chk2 (fig 1d) so that there is a correlation between binding of peptides to chk2 and chk2 stimulation; the same chk2 stimulatory peptides were also reproduced in other data throughout the paper in question and these same peptides were also used as kinase stimulators reproduced in a follow up study (10.1128/MCB.01595-06) and towards another regulatory protein (10.1016/j.molcel.2006.05.029 ).

Right-ho. It’s OK to fabricate results if you can reproduce them in your later papers. The first referenced study from Hupp’s lab has a blot duplication and a digitally assembled Chk1 gel, maybe the authors disapproved of the original results.

Ashley L. Craig , Jennifer A. Chrystal , Jennifer A. Fraser , Nathalie Sphyris , Yao Lin , Ben J. Harrison , Mary T. Scott , Irena Dornreiter , Ted R. Hupp The MDM2 ubiquitination signal in the DNA-binding domain of p53 forms a docking site for calcium calmodulin kinase superfamily members Molecular and Cellular Biology (2007) doi: 10.1128/mcb.01595-06

The second referenced paper by Hupp and Ball (Wallace et al 2006) hasn’t been yet commented upon on PubPeer, which under the circumstances of this story is no proof the paper is kosher.

What to make of the next paper though? Does any of this, uhm, reproducibility, affect the conclusions?

David Dornan , Mirjam Eckert , Maura Wallace, Harumi Shimizu, Eleanor Ramsay , Ted R. Hupp, Kathryn L. Ball Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53 Molecular and Cellular Biology (2004) doi: 10.1128/mcb.24.22.10083-10098.2004

The first author David Dornan is Hupp’s former PhD student and now Chief Scientific Officer of Bolt Therapeutics, where he “is working to harness the exciting technologies at Bolt to discover and develop therapeutics that may exploit myeloid cell biology to generate a robust anti-tumor immune response.” He also didn’t reply to my email, and neither did Bolt.

Here is another example of what Dornan learned in the Hupp lab:

David Dornan , Harumi Shimizu , Lindsay Burch , Amanda J. Smith , Ted R. Hupp The proline repeat domain of p53 binds directly to the transcriptional coactivator p300 and allosterically controls DNA-dependent acetylation of p53 Molecular and Cellular Biology (2003) doi: 10.1128/mcb.23.23.8846-8861.2003

Hupp replied to this finding in June 2021 on PubPeer that yes, the gel is digitally falsified, but it was just a control:

The authors feel that the apparent similarity likely resulted from mixing images cropped from different gels to assemble the final figure, but the original data could not be retrieved for analysis. This particular image was a negative control and does not affect the overall data interpretation or the conclusions from the study regarding interaction of p300 to proline-derived peptides, including deletion of the proline motifs of p53 that attenuate p300 functions (fig 5/6/7) and proline repeat domain protein promoter recruitment by chromatin ip (fig 8/9). The ability of proline repeat peptides to bind to p300 was also established by other studies (doi; 10.1074/jbc.M210696200; DOI; 10.1074/jbc.275.3.2115; DOI; 10.1016/j.jmb.2005.12.026; 10.1038/onc.2009.71).

Basically, controls are also there to prove that you didn’t fudge up your experiment to get the result you wanted. Hupp and his mentee Dornan failed the test.

In any case, more was found in the Dornan et al 2003 study:

There, Hupp didn’t reply anymore. Also, that Dornan et al 2003 paper shares western blots bands with another Dornan et al 2003 paper:

David Dornan , Harumi Shimizu , Neil D. Perkins , Ted R. Hupp DNA-dependent acetylation of p53 by the transcription coactivator p300 Journal of Biological Chemistry (2003) doi: 10.1074/jbc.m211460200 

Neil Perkins, now that name rings a bell. Alarm bells, actually. In 2014, Perkins, then with the Wellcome Centre of University of Dundee, retracted 4 papers, and explained in this regard to Retraction Watch that a) his postdoc Benjamin Barré did it and b) he, Perkins, exposed this fraud all by himself (OK, together with Barre’s PhD mentor). However, Perkins had already at that time several other papers flagged on PubPeer, and those were not co-authored by Barré.

Perkins’ academic career trajectory is interesting. Having spent 12 years as Dundee professor, he suddenly had enough and went to University of Bristol in 2008, but stopped being professor there after less than 2 years. Since 2010, Perkins is with University of Newcastle, where he is now deputy dean of biosciences. Meaning, all misconduct allegations in the faculty go through Perkins’ desk.

Between Hupp and Ball, the husband is the bigger academic heavyweight. In 2017, Hupp (together with a French colleague) received €9.5 Million from the Foundation for Polish Science to set up the International Centre for Cancer Vaccine Science at the University of Gdansk. Hupp runs the Centre’s Twitter account, here is his dear collaborator, the bully Argyle, visiting (right):

Any moment now will Dr Hupp’s Photoshop technology produce a cancer vaccine. Now let’s have a look at what Dr Ball’s lab enriched the science with.

Mary T Scott , Angela Ingram , Kathryn L Ball PDK1-dependent activation of atypical PKC leads to degradation of the p21 tumour modifier protein The EMBO Journal (2002) doi: 10.1093/emboj/cdf684

Maura Wallace used to head a unit at University of Edinburgh, a local newspaper once celebrated her receiving a charity donation for her cancer research. The charity money was put to good use.

Maura Wallace, Kathryn L. Ball Docking-dependent regulation of the Rb tumor suppressor protein by Cdk4 Molecular and Cellular Biology (2004) doi: 10.1128/mcb.24.12.5606-5619.2004

Well, at least we were spared Ball explaining on PubPeer that none of that data fabrication affected any conclusions, as her husband used to. Here a bit more of the Hupp and Ball game, courtesy of Clare Francis:

Jessica Pamment , Eleanor Ramsay , Michael Kelleher , David Dornan , Kathryn L Ball Regulation of the IRF-1 tumour modifier during the response to genotoxic stress involves an ATM-dependent signalling pathway Oncogene (2002) doi: 10.1038/sj.onc.1205981 
Ben Harrison , Michaela Kraus , Lindsay Burch , Craig Stevens , Ashley Craig , Phillip Gordon-Weeks , Ted R. Hupp DAPK-1 binding to a linear peptide motif in MAP1B stimulates autophagy and membrane blebbing Journal of Biological Chemistry (2008) doi: 10.1074/jbc.m706040200
Craig Stevens , Yao Lin , Ben Harrison , Lindsay Burch , Rachel A. Ridgway , Owen Sansom , Ted Hupp Peptide combinatorial libraries identify TSC2 as a death-associated protein kinase (DAPK) death domain-binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling Journal of Biological Chemistry (2009) doi: 10.1074/jbc.m805165200 
M Wallace , P J Coates , E G Wright , K L Ball Differential post-translational modification of the tumour suppressor proteins Rb and p53 modulate the rates of radiation-induced apoptosis in vivo Oncogene (2001) doi: 10.1038/sj.onc.1204496 
Nicola J. MacLaine , Bodil Oster , Bettina Bundgaard , Jennifer A. Fraser , Carolyn Buckner , Pedro A. Lazo , David W. Meek , Per Höllsberg , Ted R. Hupp A central role for CK1 in catalyzing phosphorylation of the p53 transactivation domain at serine 20 after HHV-6B viral infection Journal of Biological Chemistry (2008) doi: 10.1074/jbc.m804433200

Now, you might say, well this all looks very serious. The University of Edinburgh sure won’t like it, a research misconduct investigation is probably already under way in full steam.

What are you, born yesterday and living the Moon? University of Edinburgh is not investigating anyone, in fact they refuse to admit any notifications of suspected research misconduct so they won’t have to open any investigations. Not on the dean of the veterinary faculty, the bully Argyle, and most certainly not on Hupp and Ball. Although, Edinburgh did investigate someone once, because the external pressure got too high and because the main perpetrator was a Bulgarian woman.

The senior lecturer Irina Stancheva was dismissed. All her partners in data forgery were absolved in full and enjoy their prestigious professorships at prestigious British universities on the virtue of being British males. Even Stancheva’s retractions were coordinated as not to hurt these important gentlemen.

The research integrity guidelines at Edinburgh state:

Professor Jonathan Seckl, Vice-Principal Planning, Resources and Research Policy, is the main responsible contact for Research Misconduct. Professor Seckl  delegates responsibility for research misconduct for each College.”

Seckl never replied to my notifications of course which bureaucratically means I never submitted anything. It is worth mentioning that Seckl is a collaborator of Moshe Szyf (here a questionable paper Weaver et al 2004), and also, the Edinburgh Vice-Principal can sympathise: his brother and Imperial College London professor Michael Seckl has a nice PubPeer record, including a retraction.

That retraction Michael Seckl earned together with Julian Downward, a somewhat controversial professor at The Crick. On the occasion of his other retraction, Downward explained to Retraction Watch that, let me check, yes, “Following a series of exhaustive London Research Institute (LRI) internal and external investigations, it was concluded” that also Dr Downward became a victim of a fraudulent foreigner he nourished at his bosom. A sad and tragic fate befalling many white British men of science.

There are no dirty foreigners to blame in our Hupp and Ball game (except yours truly), so you must understand why Michael Seckl’s brother Jonathan and his Edinburgh colleagues keep disregarding my email notifications. Plus, the Institute of Genetics and Molecular Medicine where Hupp and Ball work is part of College of Medicine and Veterinary Medicine, and its head Moira Whyte has vigorously defended Argyle from bullying complaints, including from a faculty member dying of cancer.

So you see, we up some hardened and ruthless opposition in Edinburgh. Don’t get fooled by the pictures of cuddly animals they deploy. These people will bite your head off if you get too close.

But evil as I am, I found a way in.

Edinburgh may refuse to admit my notification of suspected research misconduct, but I also contacted the University of Dundee, where the Hupp and Ball game originally began in the lab of Sir David Lane. I did this recalling how in 2016 Dundee cracked down on the science fraud by their former lecturer Robert Ryan. Ryan was made to resign, his funding withdrawn, and that despite Ryan’s alma mater University College Cork in Ireland aggressively defending his research, determined to protect at all costs their professor and Ryan’s mentor (and co-author) Maxwell Dow.

So I sent the PubPeer evidence to the University of Dundee, Right away, my notification was acknowledged with this message from Paul Davies, one of university’s research integrity leads:

Thank you very much for raising this with the School of Life Sciences Research Integrity Group. As an Institution, we are proactively engaged in Research Integrity matters: we deal with the underlying causes of reproducibility issues in research and thoroughly evaluate all concerns and allegations of research misconduct involving our current and former researchers. We subscribe to PubPeer alerts (in fact we worked with PubPeer to enable searching by institution) and react to each one involving the University of Dundee.  We are aware of the published comments you highlight and we are currently looking at these and will evaluate them thoroughly.

Davies then announced to inform “all stakeholders, including the Journals, to establish the facts.” Which will first and foremost include the University of Edinburgh. Maybe Jonathan Seckl will have to grudgingly allow an investigation after all. Expect no misconduct findings though!

Photos: T. Hupp/Twitter, University of Edinburgh

Nobody in Edinburgh is answering emails, and neither does Hupp’s and Ball’s mentor Sir David Lane in Stockholm. He should though, even one of his own papers is affected.

Kathryn L. Ball, David P. Lane Human and plant proliferating-cell nuclear antigen have a highly conserved binding site for the p53-inducible gene product p21WAF1 European Journal of Biochemistry (1996) doi: 10.1111/j.1432-1033.1996.0854p.x


114 comments on “The Hupp and Ball Game

  1. Zebedee

    05 July 2022 Editor’s Note.
    https://aacrjournals.org/cancerres/article/82/13/2500/705030/Editor-s-Note-Identification-of-Src-Specific

    The editors are publishing this note to alert readers to concerns about this article (1). We were informed by the authors that in Fig. 6A, the same image showing phospho-FAK tyr-925 staining was used in error in both Fig. 6M (Vector) and Fig. 6P (SrcMF).

    Reference
    1. Brunton VG , Avizienyte E , Fincham VJ , Serrels B , Metcalf CA , Sawyer TK , et al . Identification of Src-specific phosphorylation site on Focal Adhesion Kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res 2005;65:1335–42.

    Cancer Res. 2005 Feb 15;65(4):1335-42. doi: 10.1158/0008-5472.CAN-04-1949.

    Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior
    Valerie G Brunton 1, Egle Avizienyte, Valerie J Fincham, Bryan Serrels, Chester A Metcalf 3rd, Tomi K Sawyer, Margaret C Frame

    Affiliation
    1Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow, United Kingdom. v.brunton@beaston.gla.ac.uk
    PMID: 15735019
    DOI: 10.1158/0008-5472.CAN-04-1949

    Like

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