Gianfranco Alpini, in and out of Indiana?

Rumour reached me that the Italy-born liver researcher Gianfranco Alpini ceased working at the Indiana University in USA, after merely four years there. Also his long-year special personal associate Heather Francis is said to have departed. Alpini never replied to my emails despite reminders, also Francis and even the university remained silent.

If they don’t want to talk about the situation, there is a PubPeer record of almost 50 papers by Alpini which sure provides some clues!

Alpini, with Francis and others in tow, only arrived to Indiana University in 2019. Before that, he used to be Chair in Gastroenterology at Texas A&M College of Medicine, where he had been faculty member since 1994. They arrived to Indiana announcing “to develop an internationally recognized state-of-the-art liver center” and to develop “cures for end-stage liver disease“, as a university press release from February 2019 proclaimed:

“Already established as a national leader in liver disease research, Indiana University School of Medicine has further cemented that status with the recent recruitment of three leading scientists to join the Division of Gastroenterology and Hepatology.

Led by Gianfranco Alpini, PhD, the group also includes Heather Francis, PhD, and Fanyin Meng, PhD, who come to IU School of Medicine from Texas A&M College of Medicine. The researchers bring with them $7.5 million in grant funding from agencies including the National Institutes of Health and the U.S. Department of Veterans Affairs.

Their team includes more than a dozen post doctorate investigators and technicians to staff their labs at the Richard L. Roudebush Indianapolis VA Medical Center.”

Just last year, Alpini received yet another award and a juicy research grant from the American Association for the Study of Liver Diseases (AASLD):

I am sure there are some medicine professors out there believing you can be a great doctor saving patients’ lives despite being a research cheater who forges data. After all, that’s what US medical elites seem to (wrongly) think of the MD Anderson gynaecologist and newly elected Academy member Anil Sood:

But this article is about Alpini. I can’t tell you how successful the good doctor is in treating alcoholic liver disorders, but I can tell you if he can be trusted with producing reliable preclinical science. The answer: nope.

Let’s start with two cases of re-used microscopy images, which were shifted so that the readers won’t notice.

Alpini’s former faculty colleague, the Texas A&M Medicine professor Shannon Glaser will feature on other Alpini papers you’ll see below. Also on this one, again with reused and shifted images, plus cunningly cloned western blot bands:

In a number of cases, Alpini and his co-authors replied on PubPeer. Like here, where several immunohistochemistry images look as if some minor elements had to be digitally erased and replaced with patches from elsewhere.

Heather Francis , Antonio Franchitto , Yoshiyuki Ueno , Shannon Glaser , Sharon DeMorrow , Julie Venter , Eugenio Gaudio , Domenico Alvaro , Giammarco Fava , Marco Marzioni , Bradley Vaculin , Gianfranco Alpini H3 histamine receptor agonist inhibits biliary growth of BDL rats by downregulation of the cAMP-dependent PKA/ERK1/2/ELK-1 pathway Laboratory Investigation (2007) doi: 10.1038/labinvest.3700533

Heather Francis explained on PubPeer:

“We do not have these original files due to the length of time that has passed. Regarding the staining, I’m unsure what you are insinuating? That we purposefully copied and pasted the same image/staining? Without the original files or images and without high powered examination (not PDF online file), you cannot be certain that this is an error of any kind.

regarding the blots … there are 3 options here. 1. the bands are NOT the same, 2. the bands are the same but was due to human error since the process to make figures in 2007 was not like today – multiple people were involved […] or 3. the bands are the same and it was done with intent to improve the manuscript; however, I’m unsure why this would be something to be done intentionally since these bands are TOTAL erk and the pERK is the more critical band. The graphs are clearly different. Finally, this paper was proofed by all of the authors, peer-reviewed, revised and then thoroughly reviewed by the editors and publishers – no issues were raised. This is the only way I can answer you.“

I don’t understand the logic. Because they fooled the shop detectives the stolen booze is legally theirs now? And because we won’t give you the raw data, you must drop the case? How does that work, Dr Francis? Also, there seems to be a school of thought in biomedical science that it is totally OK to fake western blot controls. Alpini can be made the deputy principal of that school, because its head can only be the Brazilian diabetes fraudster Mario Saad (who, by the way, almost became rector of his Sao Paolo university recently).

Alpini will sure be able to impress Saad. Look at this, a blot used three times between two papers, both of them have even more problems recorded on PubPeer:

Marco Marzioni , Gene D. LeSage , Shannon Glaser , Tushar Patel , Carla Marienfeld , Yoshiyuki Ueno , Heather Francis , Domenico Alvaro , Laura Tadlock , Antonio Benedetti , Luca Marucci , Leonardo Baiocchi , Jo Lynne Phinizy , Gianfranco Alpini Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats AJP Gastrointestinal and Liver Physiology (2003) doi: 10.1152/ajpgi.00398.2002 

Marco Marzioni , Yoshiyuki Ueno , Shannon Glaser, Heather Francis , Antonio Benedetti , Domenico Alvaro , Juliet Venter , Giammarco Fava, Gianfranco Alpini Cytoprotective effects of taurocholic acid feeding on the biliary tree after adrenergic denervation of the liver Liver International (2007) doi: 10.1111/j.1478-3231.2007.01443.x 

Rats suffered pain and death for fraudulent experiments. We have seen this before. In Italy as it happens:

Here is one outrageous case, a loading control used SEVEN times in 3 publications, getting closer to Saad’s record of 15 times:

Giammarco Fava , Marco Marzioni , Heather Francis , Shannon Glaser , Sharon DeMorrrow , Yoshiyuki Ueno , Antonio Benedetti, Gianfranco Alpini Novel interaction of bile acid and neural signaling in the regulation of cholangiocyte function Hepatology Research (2007) doi: 10.1111/j.1872-034x.2007.00228.x 

Marco Marzioni , Gianfranco Alpini, Stefania Saccomanno , Cinzia Candelaresi , Juliet Venter , Chiara Rychlicki , Giammarco Fava , Heather Francis , Luciano Trozzi , Shannon Glaser , Antonio Benedetti Glucagon-Like Peptide-1 and Its Receptor Agonist Exendin-4 Modulate Cholangiocyte Adaptive Response to Cholestasis Gastroenterology (2007) doi: 10.1053/j.gastro.2007.04.007 

Marco Marzioni , Heather Francis , Antonio Benedetti , Yoshiyuki Ueno , Giammarco Fava , Juliet Venter , Ramona Reichenbach , Maria Grazia Mancino , Ryun Summers , Gianfranco Alpini, Shannon Glaser Ca2+-dependent cytoprotective effects of ursodeoxycholic and tauroursodeoxycholic acid on the biliary epithelium in a rat model of cholestasis and loss of bile ducts American Journal Of Pathology (2006) doi: 10.2353/ajpath.2006.050126 

There are many more fake western blots in those three papers, if you are interested, follow the PubPeer links.

Will there be any retractions? Certainly not in the society-owned American Journal Of Pathology, and you will soon know why.

Here Team Alpini succeeded to issue a correction and to replace the offending image:

A Correction was issued in May 2023 by the learned society behind the American Journal Of Pathology, namely the American Society for Investigative Pathology (ASIP):

“The authors […] have discovered an error in Figure 3B and are replacing the panels with the images provided below. Previously published staining in the normal rat liver GnRH image had post-editing issues leading to areas of overlapping hepatocyte nuclei. While these images were not quantified and the post-editing did not alter the published analysis, the authors have chosen to replace both the normal and bile duct–ligated rat liver images stained for GnRH to maintain consistency of the staining.”

“Post-editing issues”. Data as expendable illustrations to made-up bar diagrams. What an attitude, from a learned society no less. If you are appalled, allow me to reassure you. Alpini was appointed in 2022 as Associate Editor of American Journal Of Pathology. And ASIP’s freshly elected Publications Chair who approved this nasty correction is… Heather Francis.

So you see where the learned society ASIP has its values. A similar situation, in a journal by the American Physiological Society:

Shannon Glaser , Eugenio Gaudio , Anastasia Renzi , Romina Mancinelli , Yoshiyuki Ueno , Julie Venter , Mellanie White , Shelley Kopriva , Valorie Chiasson , Sharon DeMorrow , Heather Francis , Fanyin Meng , Marco Marzioni , Antonio Franchitto , Domenico Alvaro , Scott Supowit , Donald J. DiPette , Paolo Onori , Gianfranco Alpini Knockout of the neurokinin-1 receptor reduces cholangiocyte proliferation in bile duct-ligated mice AJP Gastrointestinal and Liver Physiology (2011) doi: 10.1152/ajpgi.00418.2010

Let’s try to solve the mystery who forged the microscopy images above. From Dr Alpini’s youth:

Gianfranco Alpini , Jo Lynne Phinizy , Shannon Glaser , Heather Francis , Antonio Benedetti, Luca Marucci , Gene LeSage Development and characterization of secretin-stimulated secretion of cultured rat cholangiocytes AJP Gastrointestinal and Liver Physiology (2003) doi: 10.1152/ajpgi.00260.2002 

You saw who the first author is. How about the next paper, almost a quarter of a century old, this time Alpini is last author and Gene LeSage (briefly faculty member at University of Texas, Houston) is first:

Gene D. LeSage , Shannon S. Glaser , Luca Marucci, Antonio Benedetti , Jo Lynne Phinizy , Rebecca Rodgers , Alessandra Caligiuri , Emanuela Papa , Ziga Tretjak , Anne-Marie Jezequel , Leigh A. Holcomb , Gianfranco Alpini Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver AJP Gastrointestinal and Liver Physiology (1999) – doi: 10.1152/ajpgi.1999.276.5.g1289 

Also this paper has more problematic gels, go to PubPeer to see. I am not sure the society journal AJP Gastrointestinal and Liver Physiology will do something about the above and the following papers, because Alpini is editorial board member there.

Yuyan Han , Sharon DeMorrow, Pietro Invernizzi , Qing Jing , Shannon Glaser , Anastasia Renzi , Fanyin Meng , Julie Venter , Francesca Bernuzzi , Mellanie White , Heather Francis , Ana Lleo , Marco Marzioni , Paolo Onori , Domenico Alvaro , Guido Torzilli , Eugenio Gaudio , Gianfranco Alpini Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma: its synthesis is reduced favoring cholangiocarcinoma growth AJP Gastrointestinal and Liver Physiology (2011) doi: 10.1152/ajpgi.00118.2011 

In November 2022, an unnamed author (likely Alpini) announced on PubPeer:

“We contacted the journal making the correction on the Figures.”

No correction so far. Also for these AJP Gastrointestinal and Liver Physiology papers, corrections were announced by Alpini or his lab members months ago, but none were published yet.

You will have noticed, despite Alpini being in USA for decades, his papers have many Italian coauthors: Domenico Alvaro, Eugenio Gaudio, Paolo Onori (all at La Sapienza University in Rome); Antonio Benedetti and Marco Marzioni (University of Marche in Ancona), and others I didn’t bother to look up.

Let’s then conclude with two fraudulent papers co-authored by Alpini with his Italian friends.

A. Di Sario , E. Bendia , A. Omenetti , S. De Minicis , M. Marzioni , H.W. Kleemann , C. Candelaresi , S. Saccomanno , G. Alpini , A. Benedetti Selective inhibition of ion transport mechanisms regulating intracellular pH reduces proliferation and induces apoptosis in cholangiocarcinoma cells Digestive and Liver Disease (2007) doi: 10.1016/j.dld.2006.07.013 

Many badly fake gels here also:

Domenico Alvaro , Barbara Barbaro , Antonio Franchitto , Paolo Onori , Shannon S. Glaser , Gianfranco Alpini , Heather Francis , Luca Marucci , Paola Sterpetti , Stefano Ginanni-Corradini , Andrea Onetti Muda , David E. Dostal , Adriano De Santis , Adolfo F. Attili , Antonio Benedetti , Eugenio Gaudio Estrogens and insulin-like growth factor 1 modulate neoplastic cell growth in human cholangiocarcinoma American Journal Of Pathology (2006) doi: 10.2353/ajpath.2006.050464

There is much more on fake western blots in this paper. Like in many others by Alpini. Currently 47 publications flagged on PubPeer.

Maybe this is why Alpini is silent when asked if he indeed stopped working at Indiana University, as rumours go.

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