Dr. Edward (Ted) Sanders, who received his Ph.D. in organic chemistry in 1966, has worked in a large number of scientific disciplines, most recently epidemiology and molecular biology. After retirement from a long career at Philip Morris, both in the US and in Switzerland, he established his own consulting firm, ESScientificConsulting, during which time he has authored or co-authored five papers in these two fields. His principal current interest involves the role of metabolism in cancer, with particular emphasis on the well known Warburg effect.
To utilize published information in the area of molecular biology to provide understanding of experimental data, with a particular emphasis on the identification of druggable targets in cancer. An invaluable tool in the pursuit of this goal is his ability to use the open source bioinformatics software platform Cytoscape.
To evaluate epidemiological studies in a critical manner and to evaluate causal hypotheses using meta-analytical techniques to analyze published data.
At first glance it might appear that there is no close link between molecular biology and epidemiology. However epidemiological thinking in general and molecular biology in particular can be an invaluable tool in resolving molecular biological questions. A single example will suffice. Hoffmann-La Roche invested large sums of money into the development of dalcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor designed to increase blood levels of HDL-C, thus reducing risks of CVD.
A phase III clinical trial was started in the 1st quarter of 2011 but was terminated because of “futility” in May 2012 (Schwartz GG et al., 2012, PubMed 23126252). However, a meta-analysis published in 2008, covering studies dating back to 1970, showed a “moderate inhibition of CETP activity” and “modestly higher HDL-C levels” associated with three SNPs in the CETP gene, but little to no decrease in myocardial infarction or coronary stenosis (Thompson A et al., 2008, PubMed 18560005). Perhaps greater attention to these molecular epidemiological data could have saved considerable investment.
New Research - March 2015
There has been considerable interest in targeting gene/proteins involved in the metabolism of glucose in cancer. There is no question that many types of cancer exhibit the well-known Warburg effect, where glucose undergoes aerobic glycolysis to produce lactic acid as opposed to being metabolized to water and CO2 despite the presence of ample oxygen. We were interested in examining the Warburg effect in human cancer by comparing expression levels of the relevant genes in tumor tissue to their levels in adjacent normal tissues. In order to do this, a network was constructed using Cytoscape containing the glycolysis pathway, the gluconeogenesis pathway, the pentose phosphate pathway, the TCA cycle, the serine/glycine pathway and key steps in glutaminolysis. The expression levels of all genes in this network were then mapped onto the pathway using 10 patients with clear cell renal cell carcinoma. (CCRCC) taken from data deposited in the Gene Expression Omnibus (GSE3644). Nine of the 10 patients exhibited a classic Warburg effect. A manuscript describing this has recently been published (SandersE., S. Diehl, "Analysis and interpretation of transcriptomic data obtained from extended Warburg effect genes in patients with clear cell renal cell carcinoma," Oncoscience, 2:151-186, 2015. This manuscript details genes that are significantly over- or under-expressed in CCRCC. Perhaps the most interesting finding is that gluconeogenesis is strongly inhibited in CCRCC, which has implications with respect to pathways that branch from glycolysis, such as the serine/glycine pathway and the PPP.
Published papers by Dr. Sanders under the auspices of ESScientificConsulting:
1. Schwartz, L., M. Abolhassani, A. Guais, E. Sanders, J.M. Steyaert, F. Campion, and M. Israel, “A Combination of alpha Lipoic Acid and Calcium Hydroxycitrate Is Efficient against Mouse Cancer Models: Preliminary Results,” Onc. Rep., 23:1407-1416, 2010. PMID 20372858
2. Abolhassani, A., A. Guais, E. Sanders, F, Campion, I. Fichtner, J. Bonte, G. Baronzio, G. Fiorentini, M. Israael, and L. Schwartz, “Screening of well-established drugs targeting cancer metabolism: reproducibility of the efficacy of a highly effective drug combination in mice” Invest. New Drugs, 30:1331-42, 2012. PMID 21655919
3. Guais, A., G. Baronzio, E. Sanders, F. Campion, C. Mainini, F. Giammaria, F. Montagnani, M. Behzadi, L. Schwartz, and M. Abolhassani, “Adding a Combination of Hydroxycitrate and Lipoic Acid (METABLOC™) to Chemotherapy Improves Effectiveness against Tumor Development: Experimental Results and Case Report,” Invest. New Drugs, 30: 200-211, 2012. PMID 20931262
4. Sanders E., “Pseudohypoxia, mitochondrial mutations, the Warburg effect, and cancer,” Biomed. Res., 23:SI 109-31, 2012.
5. Sanders E., R. Weitkunat, R. Dempsey, and A. Utan, “Does the use of ingredients added to tobacco increase cigarette addictiveness? A detailed analysis,” Inhal. Tox., 24:227-245, 2012. PMID 22429143
6. sbv IMPROVER project team, Boue S., B. Fields, J.
Hoeng, J. Park, M.C. Peitsch, W.K. Schlage, M. Talikka; Challenge Best Performers (in alphabetical order), I. Binenbaum, V. Bondarenko, O.V.
Bulgakov, V. Cherkasova, N. Diaz-Diaz, L. Fedorova, S. Guryanova, J. Guzova, G. Igorevna Koroleva, E. Kozhemyakina, R. Kumar, N. Lavid, Q. Lu, S. Menon, Y. Ouliel, S.C. Peterson, A. Prokhorov, E. Sanders, S. Schrier, G.
Schwaitzer Neta, I. Shvydchenko, A. Tallam, G. Villa-Fombuena, J. Wu, I.
Yudkevich, M. Zelikman, "Enhancement of COPD biological networks using a web-based collaboration interface," F1000Res, 4:32, 2015. PMID 25767696
Top contributor in the International Crowdsourcing Network Verification Challenge, see Nature, 8 May 2014, 127, https://sbvimprover.com/challenge-3/challenge
( American Association for
Cancer Research )
(American Association for the Advancement of Science )
( American Chemical