Research integrity

Claudio and Giannino evaluate and analyze

"together with my colleagues we are actively analyzing the points raised on pubpeer." - Claudio Schneider "we will evaluate Pubpeer comments" - Giannino Del Sal

Giannino Del Sal and Claudio Schneider (no relation to me) are two great Italian cancer researchers, the former is a mentee of the latter.

Both men are EMBO members, Schneider is professor of at the University of Udine, Del Sal is professor at University of Trieste, both located in the same northern Italy province Friuli-Venezia Giulia. Del Sal is additionally since recently affiliated with the IFOM Institute of Molecular Oncology in Milan (Disclaimer: I worked there as postdoc, 2008-2012). There are also other mentees of Schneider who made impressive academic careers with bad science.

Clare Francis had a look at some old papers, the ones that established Schneider’s and Del Sal’s reputations as titans of cancer research.

Here are their often overlapping PubPeer records now, for Schneider and for Del Sal. With rotten stuff like this:

R Benetti , G Del Sal, M Monte , G Paroni , C Brancolini , C Schneider The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis The EMBO Journal (2001) doi: 10.1093/emboj/20.11.2702 

There is more in that paper, duplicated bands, inappropriate gel splicing, etc. And how can this duplication happen unintentionally:

Francesca Demarchi , Cosetta Bertoli , Peter Sandy , Claudio Schneider Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability Journal of Biological Chemistry (2003) doi: 10.1074/jbc.m305676200

Or the next study, featuring the University of Milan professor Roberto Mantovani, who has his own PubPeer record and is the nephew of the Milanese bigwig Alberto Mantovani, about whom I briefly wrote here:

The first author and Del Sal’s mentee is a Fiamma Mantovani (certainly related to Alberto and Roberto) who is presently an associate professor at the University of Trieste. She did her PhD in the lab of a certain Trieste virologist named Lawrence Banks, whom you’ll meet in the Coda of this article.

Fiamma Mantovani , Silvano Piazza , Monica Gostissa , Sabrina Strano , Paola Zacchi , Roberto Mantovani , Giovanni Blandino , Giannino Del Sal Pin1 links the activities of c-Abl and p300 in regulating p73 function Molecular Cell (2004) doi: 10.1016/j.molcel.2004.05.007 

Here, again with the same Mantovani clan member, another joint effort by Del Sal and the IRCSS Regina Elena National Cancer Institute Rome professor Giovanni Blandino:

Sabrina Strano , Olimpia Monti , Natalia Pediconi , Alessia Baccarini , Giulia Fontemaggi , Eleonora Lapi , Fiamma Mantovani , Alexander Damalas , Gennaro Citro , Ada Sacchi , Giannino Del Sal, Massimo Levrero , Giovanni Blandino The transcriptional coactivator Yes-associated protein drives p73 gene-target specificity in response to DNA Damage Molecular Cell (2005) doi: 10.1016/j.molcel.2005.04.008 

From Bufale.net

Now a paper from Schneider’s lab, featuring Roberta Benetti, a mentee of Schneider and associate professor at his University of Udine, where she collaborates with another mentee of Schneider, Claudio Brancolini (more on him later). You met Benetti at the very beginning, as the first author of another manipulated paper. Also be informed that she is being celebrated in Italy for discovering a magic cancer cure with the microRNA miR-335, which is said to replace chemotherapy. It was based on her paper Scarola et al 2010, co-authored with Schneider and Benetti’s husband, the Udine professor Stefan Schoeftner.

Roberta Benetti, Tamara Copetti , Stefania Dell’Orso , Edon Melloni , Claudio Brancolini, Martin Monte , Claudio Schneider The calpain system is involved in the constitutive regulation of beta-catenin signaling functions Journal of Biological Chemistry (2005) doi: 10.1074/jbc.m501810200

Schneider explained on PubPeer that the duplicated data was irrelevant anyway:

Thus excluding the replicate both control and experimental time courses remain intrinsically consistent We would like to remark that the graphical bug introduced in the Fig.5A does not alter the essence of the result.”

Here, I am not sure if Benetti can be blamed for the graphical bug, because Spain’s infamous super-fraudster Susana Gonzalez is on the paper! 

Roberta Benetti, Susana Gonzalo , Isabel Jaco , Purificación Muñoz , Susana Gonzalez , Stefan Schoeftner, Elizabeth Murchison , Thomas Andl , Taiping Chen , Peter Klatt , En Li , Manuel Serrano, Sarah Millar , Gregory Hannon , Maria A Blasco A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases Nature Structural & Molecular Biology (2008) doi: 10.1038/nsmb.1399

Also without Benetti, the “graphical bug” hit elsewhere, and the first author admitted intentional duplication:

Martin Monte , Marta Simonatto, Leticia Y Peche , Debora R Bublik , Stefania Gobessi , Marco A Pierotti , Monica Rodolfo , Claudio Schneider MAGE-A tumor antigens target p53 transactivation function through histone deacetylase recruitment and confer resistance to chemotherapeutic agents Proceedings of the National Academy of Sciences (2006) doi: 10.1073/pnas.0510834103 

Martin Monte and Claudio Schneider: “We see and agree we have replicated in Fig.4B the MAGE blot without specifying that it is the same blot corresponding to Fig4A. After more than 17 years, we think we introduced the MAGE panel in both Fig4A and Fig4B to render Fig4B more uniform in its capture by the reader side-by-side with Fig4A or, alternatively, it was an inadvertent error. […] this graphical bug does not alter in any way the essence of the result.”

I am sure this nasty duplication also was also meant to render the Figure 4 “more uniform”:

This one, in Nature no less, is indeed an insult. The first author Paola Zacchi spent her entire career in Trieste, and is now #opentowork on LinkedIn:

Paola Zacchi , Monica Gostissa , Takafumi Uchida , Clio Salvagno , Fabio Avolio , Stefano Volinia , Ze’ev Ronai , Giovanni Blandino , Claudio Schneider, Giannino Del Sal The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults Nature (2002) doi: 10.1038/nature01120

The upper (28S) bands in lanes 1 and 3 appear to be very similar.”

It is worth mentioning that Schneider’s and Del Sal’s Israeli collaborator Ze’ev Ronai, Chief Scientific Advisor at the Prebys Medical Discovery Institute in La Jolla, USA, has his own PubPeer record of fake science. Like this:

Pablo López-Bergami , Hasem Habelhah , Anindita Bhoumik , Weizhou Zhang , Lu-Hai Wang , Ze’ev Ronai Receptor for RACK1 mediates activation of JNK by protein kinase C Molecular Cell (2005) doi: 10.1016/j.molcel.2005.06.025

There was even more, but that fraud won’t be retracted, because the paper already received an Erratum in 2005:

“There was an error in the article title by Lopez-Bergami et al. The correct title is “RACK1 Mediates Activation of JNK by Protein Kinase C.””

Maybe the Receptor for RACK1 was the guilty party for the photoshop fraud, hence the Erratum to the title? One of Ronai lab’s papers, Buschmann et al Cell 2000, was retracted in 2002 because the authors could not reproduce their own results, the first author got the whole blame by his colleagues Ronai and Serge Fuchs (now professor at University of Pennsylvania). Well, maybe Thomas Buschmann was framed, because look:

Serge Y. Fuchs , Ze’ev Ronai Ubiquitination and degradation of ATF2 are dimerization dependent Molecular and Cellular Biology (1999) doi: 10.1128/mcb.19.5.3289 

Or maybe Buschmann was guilty, but still, this was not retracted or even corrected:

Thomas Buschmann , Dimitri Lerner , Chee-Gun Lee , Ze’ev Ronai The Mdm-2 amino terminus is required for Mdm2 binding and SUMO-1 conjugation by the E2 SUMO-1 conjugating enzyme Ubc9 Journal of Biological Chemistry (2001) doi: 10.1074/jbc.m103786200

But I digress and must return back to Friuli, Italy. Even without PubPeer, Schneider knew there were problems with some of his papers – half a year ago he issued a correction for a study not flagged on PubPeer before:

Tamara Copetti , Cosetta Bertoli , Emiliano Dalla , Francesca Demarchi, Claudio Schneider p65/RelA Modulates BECN1 Transcription and Autophagy Molecular and Cellular Biology (2009) doi: 10.1128/mcb.01396-08

Correction March 2023: “Page 2598, Fig. 2B, right: The published actin blot was taken from a different experiment and inserted by mistake. The corrected blot should appear as shown below. This change does not alter the results or conclusions of the study.”

Also Del Sal knew of problems in his papers. He had to correct a collaborative study already in 2014:

Maura Sonego , Monica Schiappacassi , Sara Lovisa , Alessandra Dall’Acqua , Marina Bagnoli , Francesca Lovat , Massimo Libra , Sara D’Andrea , Vincenzo Canzonieri , Loredana Militello , Marco Napoli , Giorgio Giorda , Barbara Pivetta , Delia Mezzanzanica , Mattia Barbareschi , Barbara Valeri , Silvana Canevari , Alfonso Colombatti , Barbara Belletti , Giannino Del Sal , Gustavo Baldassarre Stathmin regulates mutant p53 stability and transcriptional activity in ovarian cancer EMBO Molecular Medicine (2013) doi: 10.1002/emmm.201201504 

Corrigendum from 2014: “The authors of the above research article have informed the journal that an error occurred during assembly of the graphs shown in Figure 8G. The new Figure 8G below contains the correct graphs and replaces panel G of the original figure. The original statistical analyses and the P-values obtained remain valid. In any case, this mistake does not affect the results and conclusions of the paper.

The authors forgot to inform the journal that a gel was forged also, which still does not affect the results and conclusions:

I wrote to Schneider and Del Sal on 24 August 2023. The next day, on 25 August 2023, Schneider replied to me:

Dear dr. Schneider,
thanks for your email, together with my colleagues we are actively analyzing the points raised on pubpeer
.

Just minutes later, Del Sal replied also:

Dear Dr. Schneider,
thank you for your note, we will evaluate Pubpeer comments.

Some responses on PubPeer followed, but neither has ever replied to my emails again. Especially when their mentees started to post fake raw data. Look at this beauty by Schneider’s mentees Benetti and a certain Argentinian called Martin Monte whose name you keep encountering.

Martin Monte , Roberta Benetti, Giacomo Buscemi, Peter Sandy , Giannino Del Sal , Claudio Schneider The Cell Cycle-regulated Protein Human GTSE-1 Controls DNA Damage-induced Apoptosis by Affecting p53 Function Journal of Biological Chemistry (2003) doi: 10.1074/jbc.m302902200

“Figure 4E. Much more similar than expected.”

In September 2023, Monte, now back in Argentina as CONICET-funded group leader at University of Buenos Aires, posted the following reply on PubPeer. It was co-signed by Schneider, “in behalf of all authors“:

I fully support efforts towards enhancing the quality of the images that are being published, but in this case I have to disagree. The pattern indicated in the figure does not follow the logical geometry of the performed experiment. Probably, the software used to scan and analyze the image did not take into account the lines where an electrophoresis runs. If this is considered, the implied similarity does not exist (see the highlighted ovals). However, we do observe the presence of repeated pairs of points in the background of the image (see the highlighted rectangle), which could be artifacts from the image acquisition process or something that we cannot verify 20 years later. I extend my gratitude for your dedication to maintaining data accuracy and integrity.

The image posted by Monte was fraudulent. This is how bad it was:

There was more wrong with that paper. But Monte, Schneider and Del Sal remained silent. Another paper by same team, and look, the cancer miracle healer St Roberta of Udine is there as well:

Martin Monte , Roberta Benetti, Licio Collavin , Luigi Marchionni , Giannino Del Sal, Claudio Schneider hGTSE-1 expression stimulates cytoplasmic localization of p53 Journal of Biological Chemistry (2004) doi: 10.1074/jbc.m311123200

How can one half of a loading control gel be identical to the other half, just mirrored? Does this affect any conclusions? Silence.

But don’t blame Benetti alone. Monte continued publishing forged data in Argentina, I mentioned his collaboration with his colleague in Buenos Aires, Mario Galigniana, in last Friday Shorts. Here an example:

Mario D Galigniana , Alejandra G Erlejman , Martín Monte , Celso Gomez-Sanchez , Graciela Piwien-Pilipuk The hsp90-FKBP52 complex links the mineralocorticoid receptor to motor proteins and persists bound to the receptor in early nuclear events Molecular and Cellular Biology (2010) doi: 10.1128/mcb.01190-09

And now, another successful mentee of Schneider you already encountered above – Claudio Brancolini, who progressed under Schneider’s tutelage to a full professor at the same University of Udine. Based on faux science like this:

G Paroni , C Henderson , C Schneider , C Brancolini Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3 Journal of Biological Chemistry (2001) doi: 10.1074/jbc.m011565200

Bands often have vertical, straight ends between minus and plus UV treatments. Upper Jukat bands are much more similar than expected after a horizontal stretch of the rightmost band.”

Brancolini explained on PubPeer (highlights mine):

Dear Anonymus

As you can imagine, going back more than 20 years is not easy. I will try to remember. The picture shows a rapid validation screen of the antibody against caspase-2 that we developed towards the end of the last century. As you can see, there is no loading control, and the reviewers did not ask for it at that time, given the nature of the experiment. At that time, these validations were done with immunoblot strips, which were then hybridized with antibodies or different fractions of the purification cycle, also to evaluate the titer. As far as I remember, the figure in question is a compilation of these strips. It shows that the antibody we made recognizes caspase-2 and its processed form. The same result is found in other figures confirming the goodness of the antibody, and we have used this antibody in many other publications. This antibody also benefited the scientific community, as we sent aliquots of it to various colleagues upon request. I cannot rule out the problem of double banding. It is possible that a mistake was made in scanning and assembling of figure. For this I deeply apologize to the entire community. I think you will agree that this has no bearing on the scientific outcome of the work in question. If it is really necessary for the future of science, since we no longer have access to these very old data, we can repeat the experiment with Jurkat cells.”

The man just admitted data forgery but insists it doesn’t affect the conclusions because the scientific community is already greatly indebted to him. And here, same first author Gabriela Paroni, now researcher at Mario Negri Institute in Milan:

Gabriela Paroni, Michela Mizzau , Clare Henderson , Giannino Del Sal, Claudio Schneider , Claudio Brancolini Caspase-dependent regulation of histone deacetylase 4 nuclear-cytoplasmic shuttling promotes apoptosis Molecular Biology of the Cell (2004) doi: 10.1091/mbc.e03-08-0624

This is at least just as bad, shall we blame the first author maybe? Or the last?

C Brancolini, P Edomi , S Marzinotto , C Schneider Exposure at the cell surface is required for gas3/PMP22 To regulate both cell death and cell spreading: implication for the Charcot-Marie-Tooth type 1A and Dejerine-Sottas diseases Molecular Biology of the Cell (2000) doi: 10.1091/mbc.11.9.2901 

No comment there, from anyone. And this is how Brancolini continued to bless science as independent group leader:

Alessandra Fontanini , Romina Chies , Erik L Snapp , Moreno Ferrarini , Gian Maria Fabrizi , Claudio Brancolini Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-tooth 1A Gas3/PMP22 mutants Journal of Biological Chemistry (2005) -doi: 10.1074/jbc.m405104200

Brancolini and others remained silent. What is there to say indeed.

Original photos: Il Piccolo , ResearchGate

Coda

Now let’s meet Del Sal’s colleague in Trieste and an Englishman in Italy, Lawrence Banks. This virologist is Director-General of the International Centre for Genetic Engineering and Biotechnology (ICGEB) there. Banks studied and did PhD in Leeds and then went to London, where he made it to independent researcher at the Ludwig Institute for Cancer Research. Yet since 1990, he is at ICGEB, Trieste.

Banks also has a PubPeer record one should be worried about, except that he isn’t. Here a simple, but shifty example:

Ketaki Ganti , Paola Massimi , Joaquin Manzo-Merino , Vjekoslav Tomaić , David Pim , Martin P Playford , Marcela Lizano , Sally Roberts , Christian Kranjec , John Doorbar , Lawrence Banks Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 Modulates Endocytic Cargo Transport Pathways PLoS Pathogens (2016) doi: 10.1371/journal.ppat.1005854

This is how gels are done in Banks’ lab:

David Pim, Vjekoslav Tomaić , Lawrence Banks The human papillomavirus (HPV) E6* proteins from high-risk, mucosal HPVs can direct degradation of cellular proteins in the absence of full-length E6 protein Journal of Virology (2009) doi: 10.1128/jvi.00539-09

Here another nice paper by Banks:

David Pim, Justyna Broniarczyk , Martina Bergant , Martin P. Playford , Lawrence Banks A Novel PDZ Domain Interaction Mediates the Binding between Human Papillomavirus 16 L2 and Sorting Nexin 27 and Modulates Virion Trafficking Journal of Virology (2015) doi: 10.1128/jvi.01499-15  

Elisabeth Bik:Concerns about Figure 1B. The bottom panel appears to contain many repetitive features in the left two lanes.”
Bik: “Concern about Figure 3. The two Ponceau membranes look remarkably similar, with water-color-like features in the parts where they might appear different.

Banks never replied to my emails. But he does reply to journal editors:

P Massimi , L Banks Repression of p53 transcriptional activity by the HPV E7 proteins Virology (1997) doi: 10.1006/viro.1996.8315 

The lead editor of Virology shared this reply by Banks with Clare Francis and decided the case closed:

It is an old fashioned CAT assay – having run many of these around that time if several are run in the same tank there can be very similar patterns of migration. Looking closely at the image in question I feel very confident that the spots highlighted are in fact not the same.

One must take an Englishman by his word, no?

Banks also collaborated with Alan Storey, a former professor at Queen Mary University London and University of Oxford, who left academia in 2013 and works since as medical writer for changing businesses. Storey’s many forgeries are recorded on PubPeer, and his paper with Banks (Jackson et al 2020) was discussed in the following article about editorial inaction:

Now, we don’t know if Lawrence Banks had to go to Italy because he was that dishonest, or if going to Italy made his dishonesty worse, or maybe both. We also can only speculate why Claudio Schneider happened for years to be blind to the shenanigans by his mentees, while heaving them into professorships in Italy and abroad.

But really, maybe something is wrong in a country where even the minister of health is caught with fake science, where university rectors like Giorgio Zauli of Ferrara engage in massive research fraud and then abuse power and politics to defame, threaten and silence critics, and where entire universities turn into steaming fraud factories to match Chinese and Iranian papermills. As rector magnificus Salvatore Cuzzocrea did to University of Messina:

La Piovra Ferrarese di Giorgio Zauli

Giorgio Zauli’s rectorship term ends. Will research fraud, media harassment and whistleblower persecution be a thing of the past at the University of Ferrara? Ma dai, basta cazzate.


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50 comments on “Claudio and Giannino evaluate and analyze

  1. Zebedee's avatar

    Lawrence Banks (amongst others), Trieste,
    Retraction in PLoS One.

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0298249

    Like

  2. Zebedee's avatar

    It’s always lovely to see Giannino Del Sal’s work.

    PubPeer – Mutant p53 potentiates the oncogenic effects of insulin by i…

    Like

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