Exciting news in Big Pharma, only from last year: in April 2018 the French multinational Sanofi recruited the former Roche executive John Reed as their new Head of Research & Development. As media reported, Reed previously left the Swiss pharma giant Roche “for personal reasons” in March 2018. The stint at Roche in Basel was relatively short, as Reed only switched there in 2013, having left his position as CEO of Sanford-Burnham Medical Research Institute in La Jolla, California. Prior to that, Reed had a career as academic, at University of California at San Diego (UCSD), he is also member of American Association for the Advancement of Science (AAAS).
Recently the data integrity sleuth Clare Francis pointed me towards some research papers on PubPeer, most of which are from Burnham Institute and signed by Reed as corresponding last author. I personally think Sanofi should distribute these Reed papers in all their research facilities worldwide to teach their employees how to science properly. Maybe complemented by the papers of Reed’s past collaborators Paul B Fisher and Paul Dent of Virginia Commonwealth University.
Reed’s scientific expertise lies in discovering new pharmacological targets for cancer research, a huge market in pharma business, and the following representative papers show how highly efficient cancer cures can be designed with the most minimal of technological investments. Quite some of them appeared at the Journal of Biological Chemistry (JBC) which is known to be needlessly mean to successful scientists (e.g., here and here). Let’s see how it works out for Dr Reed, Head of R&D at Sanofi, whose annual salary is probably higher that the entire budget of JBC‘s academic publisher, the American Society for Biochemistry and Molecular Biology.
Let’s start with an over 20 year old classic from Burnham.
Ryosuke Takahashi, Quinn Deveraux, Ingo Tamm, Kate Welsh, Nuria Assa-Munt, Guy S. Salvesen, John C. Reed
A single BIR domain of XIAP sufficient for inhibiting caspases The Journal of biological chemistry (1998) doi: 10.1074/jbc.273.14.7787
Here Reed and colleagues identified a novel caspase inhibitory domain which can become pharmacologically relevant when a cancerously-transformed gel lane divides while acquiring a metastatic invasive propensity in a gel-figure transgression assay.
Meral Guzey, Shinichi Takayama, John C. Reed
BAG1L enhances trans-activation function of the vitamin D receptor The Journal of biological chemistry (2000) doi: 10.1074/jbc.m004977200
The authors uncovered a mechanism with which Vitamin D receptor ligand BAG1L prevents proliferation of cancer cells by mirroring the metastatic invasion activity of dividing loading control bands:
More from exactly same authors, where another Vitamin D receptor ligand, D3, proved itself as potent apoptosis inducer in cancer cells by inducing a rotational tetramer formation of the loading control:
Meral Guzey , Shinichi Kitada, John C Reed
Apoptosis induction by 1alpha,25-dihydroxyvitamin D3 in prostate cancer Molecular cancer therapeutics (2002) Jul;1(9):667-77.
Ning Ke, Adam Godzik, John C. Reed
Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak The Journal of biological chemistry (2001) doi: 10.1074/jbc.c000871200
Here the authors discovered yet another novel protein, Bcl-B which proved a potent apoptosis suppressor, likely used by cancer cells undergoing clonal expansion due to oncogene-overexpressing gel bands.
Loredana Fiorentino, Christian Stehlik, Vasco Oliveira, Maria Eugenia Ariza, Adam Godzik, John C. Reed
A novel PAAD-containing protein that modulates NF-kappa B induction by cytokines tumor necrosis factor-alpha and interleukin-1beta The Journal of biological chemistry (2002) doi: 10.1074/jbc.m200446200
Here, a novel protein termed PAN2 was discovered which mediates inflammation by promoting high-rate mitotic division activity of bands and other usually non-dividing gel elements.
Christian Stehlik, Hideki Hayashi, Frederick Pio, Adam Godzik, John C. Reed
CARD6 is a modulator of NF-kappa B activation by Nod1- and Cardiak-mediated pathways The Journal of biological chemistry (2003) doi: 10.1074/jbc.m300009200
Here, another immunomodulatory protein was discovered, CARD6. Its proliferative effects on gel bands are even more impressive, the signalling happens following the splice-event induced tertamerisation of Cardiak protein from two identical heterodimeric gel band subunits.
Han-Jung Chae, Hyung-Ryong Kim, Chunyan Xu, Beatrice Bailly-Maitre, Maryla Krajewska, Stan Krajewski, Steven Banares, Janice Cui, Murat Digicaylioglu, Ning Ke, Shinichi Kitada, Edward Monosov, Michael Thomas, Christina L Kress, Jeremy R Babendure, Roger Y Tsien, Stuart A Lipton, John C Reed
BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress Molecular cell (2004) doi: 10.1016/j.molcel.2004.06.038
Here, an inhibitor of the apoptotic protein Bax was studied, the authors discovered that BI-1 protein can prevent cell death by stimulating gel band mitotic activity in a research-integrity-refractory Molecular Cell.
Yunfei Wen, Vladislav S. Golubkov, Alex Y. Strongin, Wei Jiang, John C. Reed
Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation The Journal of biological chemistry (2008) doi: 10.1074/jbc.m708419200
Here Dr Reed probably decided to follow-up in the mysterious mitotic activities of gel bands in his previous papers and found that these were caused by a chronic Hepatitis B infection of the western blot apparatus. The virus apparently can even cause band bleaching during oncogenic band-self-replication.
Obviously Burnham institute was tremendously successful in its drug discoveries under Reed’s leadership. This is a more recent paper it published, with the director as penultimate author:
Yoshito Nagano, Toru Fukushima, Kazuo Okemoto, Keiichiro Tanaka, David D.L. Bowtell, Ze’ev Ronai, John C. Reed, Shu-ichi Matsuzawa
The authors studied here the effect of glucose starvation on research integrity, and found that the effect is devastating, while mediated by an abnormally formed Siah1-homodimer.
In 2015, Dr Reed was already in charge of an oncology branch at Roche. His Burnham lab published this, while Dr Reed provided his new Roche affiliation:
Zhifen Yang, Rachel P. Wilkie-Grantham, Teruki Yanagi, Chih-Wen Shu, Shu-Ichi Matsuzawa, John C. Reed
ATG4B (Autophagin-1) phosphorylation modulates autophagy The Journal of biological chemistry (2015) doi: 10.1074/jbc.m115.658088
Here it turned out that phosphorylation of the autophagy-relevant protein ATG4B somehow leads to one loading control being eaten. It is then replaced by a de-novo synthesised clonal actin element undergoing lightness-induced rotational cropping activity.
The following 17-year-old collaborative study of Reed’s Burnham Institute with the University of Chicago provided some mechanistic insights into the gel image complex formation process induced by rigorous drug discovery research.
Alexander H. Stegh, Bryan C. Barnhart, Jorg Volkland, Alicia Algeciras-Schimnich, Ning Ke, John C. Reed, Marcus E. Peter
Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator protein The Journal of biological chemistry (2002) doi: 10.1074/jbc.m108947200
The journal JBC namely saves images in pdf as they were submitted, so if an image is a composite one, it can be disassembled into the individual images it was made of. Some gels proved to consist of several malfunctional subunits, assembled by a hitherto unknown novel mechanism. Reed’s Burnham Institute apparently decided more research was needed, see above and here on PubPeer, a total of 40 papers from between 1998 and 2015.
I think Sanofi made a genius choice with Dr Reed as their Head of R&D, every patient should flip from excitement and at least double or even four quadruplicate their trust into Sanofi’s research and novel therapies now. And as the high achiever Reed himself teaches, successful pharma research depends on sacking people who do not perform:
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