Cellular metabolism is comprised of a network of interconnected biochemical reactions resembling a subway system. Zhaoqi Li compares normal and diseased cells to determine the differences in the way nutrients travel through this network. Credit: Justin Chen<\/figcaption><\/figure>\n– –<\/p>\n
Although he is new to the community of researchers specializing in metabolism, Li has long known that he wanted to interact with the world through science. As an immigrant who moved from China to southern Tennessee at the age of six, Li struggled to learn English and began to view science as a universal language that transcended culture.<\/p>\n
\u201cMy parents were also non-native speakers and the English as a Second Language classes in my elementary school were geared towards Spanish speakers, so I had a really hard time,\u201d Li says. \u201cI joke that the only reason I passed the first grade was because I was good at math.\u201d<\/p>\n
Li\u2019s contrasting relationship with science and English continued as an undergraduate at Columbia University. There he majored in biochemistry and also studied literature of the Western Canon to fulfill his general degree requirements.<\/p>\n
\u201cI took four semesters worth of classes that started with Plato and ended with Virginia Woolf,\u201d he says, \u201cIt was an eye-opening experience, but I never really loved it. I found biology more intuitive because it doesn\u2019t rely on being familiar with a specific cultural lens. Most every society in the world values the scientific method to some extent.\u201d<\/p>\n
Li began working in a lab during his sophomore year at Columbia. To his surprise, he was mentored by a professor who valued his input and encouraged creative thinking. Li\u2019s supervisor also introduced him to basic science \u2014 a type of research driven not by the desire to find a specific answer or cure, but by curiosity and the need to better understand the natural world.<\/p>\n
– –<\/p>\n
During his second semester rotation at MIT, Li searched for similarly open-minded environments, and was attracted to cancer metabolism because the field was relatively young.<\/p>\n
\u201cIn other more established areas of biology, if you have a question someone has probably answered it in some capacity,\u201d Li says. \u201cThe Vander Heiden lab was using new techniques so there was a lot of space to explore. Many questions I asked \u2014 even during my initial rotation \u2014 \u00a0didn\u2019t have an answer, which was exciting.\u201d<\/p>\n
The great challenge confronting the metabolism field is translating decades\u2019 worth of research on enzymes \u2014 proteins that manage chemical reactions \u2014 from the test tube to the cell and human body. By studying enzymes individually in the controlled setting of test tubes, researchers have documented almost all the chemical reactions that occur in the cell. When combined, these reactions look like a giant subway map where each stop, indicated by a dot, is a different molecule, and the line between stops represents a chemical reaction where atoms are added or subtracted. Some pathways are a straight line but others have nodes or intersections where a molecule can take part in several different reactions. Other pathways are circular where the molecule that starts the pathway is remade at the end so that the line circles back on itself.<\/p>\n
Despite the ability to study chemical reactions in a test tube, scientists have struggled to understand what is actually happening in the complex environment of cells, which coordinate millions of reactions that not only affect each other, but are also influenced by outside stresses like nutrient deprivation.<\/p>\n
To Li, using the metabolism map to figure out what chemical reactions are occurring and how atoms are moving through the cell is like using a subway map to track how people are traveling through a city.<\/p>\n
\u201cThe map describes all the possible routes people could take,\u201d Li says, \u201cbut you have to track the passengers to figure out where they are actually going. You could imagine people commuting into the city during the week and going to entirely different places on the weekend. There are a lot of different patterns of movement that you can\u2019t infer just from looking at a map.\u201d<\/p>\n
To analyze what chemical reactions are occurring in the cell, Li utilizes cutting edge technology to track carbon atoms \u2014 an essential element that is required to build all components of the cell. By tagging carbon with an extra neutron, Li makes the experimentally altered atom heavier and distinguishable from naturally occurring carbon in the cell. Feeding cells nutrients like glucose made with heavy carbons allows Li to compare how molecules are broken down and used by normal and cancerous cells.<\/p>\n
\u201cReturning to the subway map analogy, this labeling technique is similar to not only being inside the subway, but also giving everyone in Downtown Boston a red shirt,\u201d Li says. \u201cAfter 12 hours, we can look at the rest of the city. If we see a lot of red shirts in Allston, we would know that this particular route is really popular.\u201d<\/p>\n
In the case of glucose, Li and his labmates observed that normal cells break down the sugar to release energy and heavy carbons in the form of carbon dioxide. In contrast, cancer cells alter their metabolism so that the heavy carbons originally found in glucose are used to build new parts of the cells that are required for cancer cells to grow, such as membranes, DNA, and proteins.<\/p>\n
Li\u2019s observations demonstrate how cancer cells sustain abnormal growth by accumulating carbon. For his thesis project, Li has chosen to investigate one of the main tricks cancer cells use to hoard carbon atoms: a process known as carbon fixation. This type of chemical reaction, originally studied in plants performing photosynthesis, attaches carbon dioxide to other molecules. Li\u2019s initial findings suggest that a protein, Malic Enzyme 1, helps cancer cells use carbon dioxide to build components required for growing and dividing.<\/p>\n
\u201cThis is surprising,\u201d he says, \u201cbecause the textbook version of this enzyme actually catalyzes the reverse reaction in normal cells where carbon dioxide is removed from molecules. \u00a0Malic Enzyme 1 is an example of how cancer performs remarkable chemical reactions \u2014 who would have thought that cancer cells use carbon like plants do?\u201d<\/p>\n
Li is at the beginning stages of his research, and can\u2019t predict where his project will take him. His current goal is to determine how cancer cells react when they are missing Malic Enzyme 1. Such loss could slow growth, but Li will have to perform experiments to be sure, since cancer is a resourceful and elusive target.<\/p>\n
Like a detour rerouting travelers around a closed metro stop, cancer cells may further contort their metabolism, taking advantage of little-used or still unidentified chemical reactions to maintain growth. In the face of such adaptability, Li and his labmates believe the best course of action is to be as curious as possible to understand as much as they can about how cancer works. Working together, they discuss confounding results, adjust hypotheses, and design new experiments.<\/p>\n
\u201cIt\u2019s really encouraging to be part of Matt\u2019s lab and the Koch Institute in general where researchers take a basic science approach,\u201d Li says. \u201cWe try to keep an open mind because there\u2019s probably no single thing that cancer cells depend on. Everyone\u2019s work builds together to form a cumulative understanding.\u201d<\/p>\n
Photo credit: Raleigh McElvery \nPosted: 1.11.18<\/h5>\n Why MIT Biology?<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Sizing up cancer Graduate student Zhaoqi Li investigates how cancer cells grow by harnessing exceptional chemical reactions. Justin Chen Cancer cells use extreme measures to fuel their growth. In fact, researchers like Zhaoqi Li, a third-year graduate student, witness chemical reactions in these cells that would be impossible in the context of normal cells. […]<\/p>\n","protected":false},"author":16,"featured_media":0,"parent":1247,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-5240","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\n
Profile: Zhaoqi Li - MIT Department of Biology<\/title>\n \n \n \n \n \n \n \n \n \n \n \n \n\t \n