first entry.

One of the first things Dr. Ronald A. DePinho, the institution’s president, told me when I arrived at The University of Texas MD Anderson Cancer Center was that everyone here eats, sleeps, and breathes cancer research. Every person is reading journal articles, treating patients, attending seminars, leading discussions, and ultimately trying to find a cure. Every moment we spend at the cancer center allows the center to dictate what we think or talk about and what we want to define us. The macro-environment at MD Anderson is extremely impactful in cancer biology and oncology because the institution is devoted to the integration of basic science research, technology, and education. In my first few weeks here, I have been able to analyze many different dimensions of biological space because, in essence, I have become like everyone else at the institution: devoted to cancer abolition.

Since arriving on June 5th, even the lab I am working in has stressed the institution’s goals, among their many other goals. The joint lab of Dr. Anirban Maitra and Dr. Sonal Gupta puts an emphasis on educating students because the lab believes that young scientists will be the ones to eventually find a cure for pancreatic cancer. Thus, one of the things I was most awestruck by was the number of individuals working in the lab. The individuals ranged from visiting professors from other institutions, postdoctoral fellows, graduate students, and research technicians, to other summer trainees like myself. They were students of all ages in this macro-environment ready to learn from each other.

The Maitra lab has over ten ongoing projects and a myriad of instruments that serve to expedite data generation, collection, and analysis. The access to this type of equipment, I learned, gives the lab the ability to make meaningful conclusions at a rapid pace. However, most of their projects boil down to answering one overarching question: what drives epigenetic dysregulation in pancreatic cancer, and how can we combat it? Finding an answer to this question is extremely important because pancreatic cancer is the fourth-leading cause of death in the United States.

My project for the summer is to develop an answer to an aspect of this question. I am attempting to understand the significance of enhancer of zeste homolog 2 (EZH2) in pancreatic cancer. EZH2 is the catalytic subunit of polycomb repressive complex 2 (PRC2), and it functions to maintain transcriptional repression of certain genes. In early development, EZH2 is involved in repressing certain genes to allow differentiation to occur. This is the only time when large amounts of EZH2 are present in cells. Later on, in healthy adults that are fully developed, EZH2 levels are kept low. However, in many cancer types, EZH2 becomes overexpressed, meaning that it is repressing the transcription of many genes (such as tumor suppressor genes) abnormally, leading to increased proliferation and tumorigenesis. EZH2 does this without changing nucleotide sequences. In fact, this is what cancer epigenetics is all about – the modification of histones. More specifically, EZH2 can methylate, a type of histone modification, which can be integral in repressing the function of a gene. We have yet to understand by what and how EZH2 is regulated in cancer.

I am in the process of knocking down EZH2 using shRNA in a specific pancreatic cancer cell line (KMC cells which have mutant Kras and MLL3 deletion). I transformed E. Coli to incorporate foreign DNA into their genome, this foreign DNA being a vector containing the shRNA of interest. I allowed the E. Coli to produce plasmid. I then transfected competent 293T-cells, meaning that I allowed these mammalian cells uptake the plasmid. These cells produced lentiviral clones. I finally transduced the KMC cell line with the lentiviral clones in order to incorporate the shRNA into this line so that EZH2 expression is knocked down. I am currently in the process of performing qRT-PCR and immunoblotting to determine whether I was successfully able to knockdown EZH2 in these cells. If so, I will proceed forward in determining how this knockdown of EZH2 affects the expression of its target genes in KMC cells. I expect to eventually follow up with knockdowns in two other pancreatic cancer cell lines and knockouts of EZH2 using CRISPR-Cas9. The data I collect will hopefully corroborate functional assays done previously showing that if you inhibit EZH2, you will be able to obstruct pancreatic cancer cell growth, which has huge implications in translational medicine.
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The techniques I have mastered and the concepts I have learned so far would not have been possible without the help and guidance of scientists in the lab. Therefore, one thing I understand now is that scientific research is more than just about generating data. Scientific research is about educating those around you devoted to the same cause. Moreover, I think that health disparities across the globe can only be overcome by educating individuals about disease. Science education should not be a luxury that only those with access to schooling should have. Rather, to level health disparities we must use technology to educate many people about treatments and preventative measures and demystify the myths that surround our health. It is particularly important now more than ever because in the last century life expectancy has doubled, but there has also been an equal or greater increase in disease, including cancer.

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