Arielle Tripp, Post 1

MARC SUMMER BLOG, 

Greetings from Boston, Massachusetts. My name is Arielle Tripp and I am a rising junior studying Human Biology & Society and Neuroscience. Currently, I am conducting research in the Neurosurgery department at Brigham and Women’s Hospital as part of the Summer Training in Academic Research and Scholarship (STARS) program. My research is investigating the different pharmacokinetics (the movement of a drug into, through, and out of the body - what the body does to a drug) and pharmacodynamics (what a drug does to the body) properties of the drug, CGM097, on brain tumors within a mice model. CGM097 functions as an inhibitor of MDM2, aka Mouse Double Minute 2 Homolog. The MDM2 gene is an oncogene and plays a role in tissue development. The MDM2 protein functions as a negative regulator of transcriptional factor p53, a tumor suppressor. The protein expression of MDM2 and p53 is inversely related; an increase in MDM2 results in a decrease in p53 and vice versa. Normally, p53 functions as a powerful tumor surveillance mechanism; it regulates cell cycle, apoptosis, DNA repair and senescence. Mutations, however, can cause this system to go awry. For example, overexpression of MDM2 can result in cell over growth, tumorigenesis, and malignant transformation of cells. For this reason, MDM2 inhibitor drugs are essential in order to decrease its expression in cancerous tissue.

Therefore, my project is using mass spectroscopy analysis to do two things. First, we are analyzing the ability of the drug CGM097 to cross the blood brain barrier (BBB) and reach cancerous brain tissue. Secondly, once the drug has crossed the BBB, we are analyzing what its specific lipid and protein targets are within the cancerous tissue. The big picture goal of the project is to be able to develop a unique lipid and protein profile for brain tumors. Such a profile would allow a neurosurgeon, for instance, to take a sample of a patient’s brain during an operation and through mass spectroscopy analysis, evaluate whether the sample is cancerous or healthy tissue. This is amazing! One of the main obstacles remaining today in the field of neurosurgery is that during an operation often it is almost impossible to distinguish between healthy and cancerous tissue because they often look remarkably alike. Previously, the only way to view and locate the margins of a brain tumor was through continuous imaging; limitations of which included the possibility of cutting out healthy tissue, or leaving cancerous tissue behind.

Another big picture idea, more closely related to my project, is the ability of scientists to map within the brain the efficiency of anticancer drugs. Prior to the innovation of mass spectroscopy analysis of the pharmacodynamics and pharmacokinetics properties of drugs, there weren't very good ways to observe and empirically quantitate a drug’s performance. I don’t know much about technology used prior to mass spectroscopy for such analysis, so I will highlight its advantages instead. One of the great things about mass spectroscopy is that it allows you to create an image of a brain with localized signals, accurately depicting the precise location of a drug within a tissue section. In my next post I will go into further detail about how exactly a mass spectrometer works. For now, let me just say that the technology is quite fantastic. It allows high resolution imaging of every single molecule present in a tissue sample. Therefore, allowing a wide variety of lipids, proteins, small drug metabolites, and blood to be easily differentiated between. The applications are limitless, though I will discuss a few in my next post about the mechanism of mass spectroscopy.

In closing, I’m enjoying my summer research program. It rains every once in a while, but I don’t mind; it’s nice to experience rain after being out in the desert that is California for so many years. This post was supposed to also cover some aspect of my personal experiences outside of lab - I’ll make sure to touch on that in the next post. As well as, some of the clinical shadowing and other events I’ve been able to attend as part of the BWH STARS program. Wishing everyone a great summer. Best, Arielle Tripp.

 

Pictured are my roommates and I under the Harvard Medical School (HMS) sign. The BWH STARS is one of many programs run by HMS during the summer. Although only the four of us are pictured, my program has a total of ten scholars. Three of which are medical students, and the rest are undergraduates from universities across the nation.

This is an image of a mice brain section imaged with a MALDI- FTICR mass spectrophotometer.  The green signals represent the presence or drug, while the red signals represent the presence of blood.