Interview with Dr. Samson T. Jacob, Retired Ohio State University Professor

Retired Ohio State University Professor

Below is a recent interview with Dr. Samson T. Jacob, Retired Ohio State University Professor

Please tell us a little more about yourself.

My name is Dr. Samson T. Jacob, and I am a retired Ohio State University Professor. I have many teaching, research, and leadership accomplishments under my belt.

What was your expertise? As a professional, what would you say was your unique value proposition?       

Here I will focus on my research accomplishments: 

My research interests include transcriptional and epigenetic regulation in cancer, particularly hepatocellular (liver) carcinogenesis. I have published extensively in this and related fields in well-established/high-impact journals. 

A book on Enzymes of Nucleic acid Synthesis and Modification (two volumes) was also edited by me.

In cancer, ribosomal RNA precursor processing and ribosomal RNA synthesis are significantly higher than in normal tissues. My research resulted in the characterization of transcription factors and RNA polymerase. I was involved in the ribosomal RNA gene expression and its role in tumorigenesis, particularly in hepatocellular carcinogenesis.

In my laboratory, a seminal discovery was the differential response of alpha amanitin (a toxin found in wild mushrooms) to mammalian RNA polymerases. This allowed me to selectively analyze the transcription of genes by three distinct RNA polymerases. Moreover, this study provides one of the earliest indications that eukaryotic RNA polymerases can exist in multiple forms.

It was also my laboratory that discovered the first mitochondrial Poly (A) polymerase that was subsequently linked to mitochondrial polyadenylation. 

My laboratory demonstrated coupled cleavage and polyadenylation of pre-mRNA, an important concept in the field of mRNA processing. A large part of our research also involved the characterization of nuclear poly (A) polymerases from normal liver cells and human liver tumor cells.

We have done pioneering work in the epigenetic silencing of tumor suppressor genes. This study led to the discovery that the protein tyrosine phosphatase is a bona fide tumor suppressor that is silenced in chronic lymphocytic leukemia (cell lines, mouse models, and primary human CLL), hepatocellular carcinoma (cell lines, rodent models, and primary human HCC) and breast (cell lines and primary human breast cancer). We also demonstrated the role of the truncated form of this enzyme (PTPROt) in the negative regulation of Bcr-Abl signaling in chronic myeloid leukemia (CML). Our lab identified many novel substrates of this enzyme. This included the tyrosine kinases Lyn and ZAP70. The altered phosphorylation of these substrates contributed to CLL tumorigenesis. 

Our laboratory studied extensively the role of metallothionein (MT) in hepatocellular carcinoma. Our study demonstrated the protective role of MT in the DEN- (Diethyl nitrosamine) induced model of HCC using MT knockout (MT KO) mice.

We established microRNA signature at early stages of hepatocarcinogenesis (HCC) using mouse models of diet-induced liver cancer. We also showed drastic suppression of gluconeogenesis in liver cancer that potentially contributed to very high levels of glycolysis called the Warburg effect. We also elucidated the mechanism of altered metabolism in liver cancer.

We demonstrated that the miRNA (miR-1) gene can also be epigenetically silenced by promoter methylation (like protein-coding genes) and can be re-activated by DNA hypomethylating agent in hepatocellular carcinoma. This study provided a novel molecular target for HCC therapy.

We characterized novel nonnucleoside quinoline compounds that can function as DNA hypomethylating agents with minimal incorporation into DNA that may probably reduce their toxicity. This study offers a novel approach to treat some types of cancer. 

We established the role of miR221/222 in tamoxifen resistance and elucidated its mechanism (published in J.Biol. Chem. This paper was selected as the paper of the week). This was the first demonstration of the role of a miRNA in drug resistance. Overexpression of miR221/222 has now been attributed to the resistance of different human cancers to other potent anticancer drugs.

Another fundamentally significant finding in my laboratory was the inhibition of hepatoma cell proliferation and growth by Zerombone, an active ingredient of the ginger plant. We also elucidated the molecular mechanism by which it inhibits cancer cell growth. A key observation was that it inhibited glucose consumption which is essential for tumor growth. These findings reveal a novel and potentially effective therapeutic strategy for liver cancer using a natural product. 

What did a typical day look like for you? How did you stay productive and efficient consistently?

I am up quite early in the morning. I meditate for a while, have a cup of coffee, review the world and national news briefly, and spend considerable time reviewing the latest trends in science, particularly in the cancer field, the field of my interest for more than five decades until I retired in 2021. 

What was it about the field that held your interest and motivated you to continue in it? 

The field of cancer has come a long way. I have personally seen the sufferings of cancer patients and was always keen to find the best possible ways to address a therapeutic regimen based on solid research data. The early diagnosis of many types of cancer and discoveries of new chemotherapeutic regimens, as well as other ways to prevent the progression of cancer at an early stage, has brought considerable hope to patients and oncologists. 

Which professional accomplishment or success story are you most proud of? What stands out as one of your most notable achievements?

In addition to my research accomplishments, I had major administrative roles in three universities. I was the Co-Director of the Specialized Cancer Research Center at the Pennsylvania State University College of Medicine, Chair of the Department of Pharmacology and Molecular Biology at the Chicago Medical School (Currently called Rosalind Franklin University of Medicine), and Chair of the Department of Molecular Cellular Biochemistry (Currently called Department of Biological Chemistry and Pharmacology), C-Director of Experimental Therapeutics Program of the Comprehensive Cancer Center and the first Director of the Intramural Research Program at Comprehensive Cancer Center, Wexner Medical Center, The Ohio State University.

My dedication to these jobs enabled me to raise the standards of the departments and programs I chaired or directed.

Can you name a particular challenge or obstacle that tested your mettle and what you did to overcome it?

While hard work and dedication to research and other academic responsibilities are critical to the success of anyone who aspires to do the best in their career, unnecessary and counterproductive interference from external sources is hampering the progress of scientific research. If these issues are not corrected, we are likely to lose a whole generation of young scientists who will seek other professions. 

What would you say are some essential skills needed to be successful in your specialized field?

 In addition to your own dedication to your field of interest, it is critical to recruit equally dedicated young scientists who are passionate about their research and are determined to address the key issues. They should also be trained to follow the guidelines established for fairness and honesty to achieve the desired goals. At the same time, you must always exhibit your leadership and mentorship. 

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