Mentoring and Medicine | MIT News

During the spring 2020 virtual semester, Daniel Zhang, a biology senior, put his time at home to good use. In the garage of his home in San Diego, California, Zhang helped his 13-year-old brother build a lab to study dry eye disease.

This combination of mentorship and medicine seems like second nature to Zhang. When her parents opened a family optometry clinic, Zhang was their first patient and then their receptionist. And after a close family member died of leukaemia, he remembers thinking, “Humans are susceptible to so many diseases, why don’t we have better cures?”

This question prompted him to spend his summers in high school studying biomarkers for the early detection of leukemia at the University of California, San Diego. He was invited to present his research at the London International Youth Science Forum, where he spoke with scientists from nearly 70 countries. Thereafter, he became addicted to the idea of ​​making scientific research a career.

“Research is like standing on the shoulders of giants,” he says. “My forum experience was when I knew I loved science and wanted to continue using it to find common ground with other people from completely different cultures and backgrounds.”

Explore the cutting edge of cancer research

Upon arriving at MIT as a first-year undergraduate, Zhang began working under postdoctoral fellow Peter Westcott in the lab of Professor Tyler Jacks. The lab is focused on developing better mouse and organoid models to study cancer progression – in Zhang’s case, metastatic colorectal cancer.

One way to model colorectal cancer is to inject a modified virus directly into the colon of mice. The viruses, called lentiviral agents, “knock out” tumor suppressor genes and activate so-called oncogenes that advance cancer. However, the imprecise nature of this injection also unintentionally turns many “off-target” cells into cancerous cells, producing far too widespread and aggressive cancer. Additionally, rare tumors called sarcomas often initiate rather than adenocarcinomas, the type of tumor found in 95% of human cases. As a result, these mouse models are limited in their ability to accurately model colorectal cancer.

To solve this problem, Zhang and Westcott devised a method using CRISPR/Cas9 to target a special stem cell called LGR5+, which the researchers believe are the types of cells that, when mutated, turn into colorectal cancer. His technique only modifies LGR5+ cells, which would allow researchers to control the growth rate of adenocarcinomas. Therefore, it generates a model that is not only much more similar to human colorectal cancer than other models, but also allows researchers to quickly test other potential cancer genes with CRISPR/Cas9. Designing an accurate model is crucial for developing and testing effective new therapies for patients, Zhang says.

During MIT’s virtual spring and fall semesters in 2020, Zhang shifted her focus from lab-based lab work to computational biology. Using patient data from the Cancer Genome Atlas, Zhang analyzed mutation rates and found three genes potentially involved in colorectal cancer tumor suppression. He plans to test their function in his new mouse model to further validate how dysfunction of these genes drives colorectal cancer progression.

For his work on organoid modeling of colorectal cancer, a third project he worked on during his time at the Jacks lab, he was also recognized by the American Association for Cancer Research (AACR). As one of 10 Undergraduate Scholar Award winners, he had the opportunity to present his research at the AACR Virtual Conference in 2021 and again at the next AACR conference at New -Orléans in April 2022.

He credits MIT’s “mens and manus” philosophy, encouraging the practical application of knowledge, with much of his early success in research.

“I found that at MIT, a lot of people are pursuing projects and asking questions that they had never thought of before,” Zhang says. “No one has ever been able to develop an advanced stage model of colorectal cancer that is amenable to gene editing. As far as I know, apart from us, no one in the world is even working on this.

Inspire future generations to pursue STEM

Outside of the lab, Zhang spends a lot of time sharing the science that he is so passionate about. Not only did he receive the Gene Brown Undergraduate Teaching Award for his time as a teaching assistant for lab class 7.002 (Foundations of Experimental Molecular Biology), but he also took on leadership roles. leadership in science popularization activities.

During the 2020-21 academic year, he served as co-director of DynaMIT, an outreach program that runs a two-week STEM program over the summer for underserved students in grades six through nine in the greater Boston area. Although the program traditionally takes place in person, in the summer of 2021 it was held virtually. But Zhang and the rest of the board didn’t let the virtual format deter them from maximizing the fun and interactive nature of the program. They packed and shipped nearly 120 science kits focused on five major subjects — astronomy, biology, chemistry, mechanical engineering and math — allowing students to explore everything from paper rockets to catapults and trebuchets to homemade ice cream.

“At first, we were concerned that most students would turn on their cameras, because we saw this trend in all MIT classes during the semester,” says Zhang. “But almost everyone had their camera on all the time. It was really gratifying to see some very shy students arrive on Monday, but by Friday, be actively involved, crack jokes with the mentors, and get really excited about STEM.

To study the long-term impacts of the program, he also helped start a project that tracked DynaMIT alumni, some of whom have already graduated from the university. Zhang says, “We were happy to see that 80-90% of DynaMIT alumni enjoyed the program, rating it four or five out of five, and nearly 70% of them said DynaMIT had had a really positive impact. on their path to a career in STEM.

Zhang also served as president of the MIT Pre-medical Society, with the goal of fostering an encouraging environment for undergraduate pre-medical students and providing guidance and resources to freshmen and sophomores still undecided on the path. of premedicine. To achieve these goals, he launched an MIT-hosted blender with the premedical societies of other Boston colleges, including Wellesley College, Boston University, Tufts University, and Harvard University. At the mix, students were able to network with each other and listen to guest speakers from different universities talk about their experiences in medicine. He also launched a “big/small” initiative that pairs third- and fourth-year mentors with first- and second-year students.

Offer new opportunities and hope

The wealth of activities Zhang participated in at MIT informed her choices for the future. After graduation, he plans to take a year off and work as a pediatric oncology research technician before applying for MD/PhD programs.

On the mentoring side, he is currently working on setting up a non-profit organization called Future African Scientist with his former Ugandan roommate, Martin Lubowa, whom he met while on a study abroad program during MIT’s period of independent activities in 2020. The organization will teach high school students in Africa. professional skills and exposing them to different STEM subjects – a project Zhang plans to work on after MIT and in the long term.

Ultimately, he hopes to lead his own lab at the intersection of CRISPR-Cas9 technology and cancer biology, and serve as a mentor to future generations of researchers and physicians.

As he says, “All the experiences I have had so far have solidified my goal of conducting research that impacts patients, especially young people. Being able to bring new opportunities and hope to patients with advanced metastatic disease without current treatment is what inspires me every day. »