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Mentorship and medicine | MIT News

All through the digital spring 2020 semester, Daniel Zhang, a senior majoring in biology, put his time at residence to good use. In the garage of his home in San Diego, California, Zhang assisted his 13-12 months-old brother establish a lab to analyze dry eye disease.

This blend of mentorship and medication feels like next mother nature to Zhang. When his dad and mom opened a relatives-operate optometry clinic, Zhang was their 1st affected person and then their receptionist. And just after a near spouse and children member passed absent from leukemia, he remembers considering, “Humans are inclined to so many disorders — why really don’t we have greater cures?”

That dilemma propelled him to expend his large school summers finding out biomarkers for the early detection of leukemia at the University of California at San Diego. He was invited to existing his study at the London International Youth Science Discussion board, the place he spoke to experts from pretty much 70 nations. Afterward, he was hooked on the thought of scientific research as a vocation.

“Research is like standing on the shoulders of giants,” he states. “My working experience at the discussion board was when I realized I cherished science and desired to continue on working with it to come across common floor with some others from totally unique cultures and backgrounds.”

Discovering the forefront of cancer analysis

As quickly as he arrived at MIT as a 1st-year undergraduate, Zhang started performing beneath the direction of postdoc Peter Westcott in professor Tyler Jacks’ lab. The lab focuses on building superior mouse and organoid versions to examine cancer development — in Zhang’s circumstance, metastatic colorectal cancer.

One particular of the methods to product colorectal cancer is by injecting an engineered virus specifically into the colons of mice. The viruses, referred to as lentiviral brokers, “knock out” tumor suppressor genes and activate the so-named oncogenes that generate most cancers ahead. However, the imprecise mother nature of this injection also unintentionally transforms a lot of “off-target” cells into most cancers cells, developing a most cancers that is significantly as well common and intense. In addition, scarce tumors named sarcomas are generally initiated rather than adenocarcinomas, the style of tumor located in 95 p.c of human instances. As a outcome, these mouse types are minimal in their means to accurately model colorectal cancer.

To tackle this problem, Zhang and Westcott created a method making use of CRISPR/Cas9 to concentrate on a special stem mobile identified as LGR5+, which scientists believe that are the sorts of cells that, when mutated, increase into colorectal cancer. His system modifies only the LGR5+ cells, which would let researchers to manage the charge at which adenocarcinomas grow. Thus, it generates a product that is not only a lot much more related to human colorectal cancer than other models, but also makes it possible for scientists to swiftly exam for other prospective cancer driver genes with CRISPR/Cas9. Creating an precise model is important for establishing and tests effective new therapies for clients, Zhang states.

For the duration of MIT’s digital spring and tumble semesters of 2020, Zhang shifted his focus from benchwork in the lab to computational biology. Employing affected person knowledge from the Cancer Genome Atlas, Zhang analyzed mutation fees and uncovered a few genes probably included in colorectal cancer tumor suppression. He options to check their operate in his new mouse design to further more validate how the dysfunction of these genes drives colorectal cancer development.

For his perform on organoid modeling of colorectal cancer, a third challenge he’s worked on throughout his time at the Jacks lab, he also won recognition from the American Association for Most cancers Analysis (AACR). As a single of 10 winners of the Undergraduate Scholar Award, he had the prospect to existing his research at the virtual AACR conference in 2021 and once again at the upcoming AACR Convention in New Orleans in April 2022.

He credits MIT’s “mens et manus” philosophy, encouraging the fingers-on application of expertise, as a huge section of his early success in exploration.

“I’ve uncovered that, at MIT, a whole lot of men and women are pursuing initiatives and asking concerns that have never been considered of right before,” Zhang claims. “No one has at any time been able to produce a late-stage design for colorectal most cancers that’s amenable to gene enhancing. As considerably as I know, other than us, no just one in the globe is even functioning on this.”

Inspiring upcoming generations to pursue STEM

Outside the house of the lab, Zhang devotes a substantial amount of money of time to sharing the science he’s so passionate about. Not only has he been awarded the Gene Brown Prize for undergraduate educating for his time as a teaching assistant for the lab class 7.002 (Fundamentals of Experimental Molecular Biology), but he’s also taken on leadership roles in science outreach routines.

Throughout the 2020-21 academic 12 months, he served as co-director of DynaMIT, an outreach method that organizes a two-7 days STEM application above the summer months for underserved sixth to ninth graders in the better Boston place. Although the method is usually held in-particular person, in summer months 2021 it was held nearly. But Zhang and the relaxation of the board didn’t enable the virtual structure discourage them from maximizing the exciting and interactive character of the system. They packed and shipped just about 120 science kits concentrated on 5 big matters — astronomy, biology, chemistry, mechanical engineering, and math — enabling the learners to investigate everything from paper rockets to catapults and trebuchets to do-it-yourself ice cream.

“At first, we ended up worried that most of the college students wouldn’t flip on their cameras, considering that we noticed that craze all in excess of MIT courses in the course of the semester,” Zhang suggests. “But almost absolutely everyone experienced their cameras on the whole time. It was really gratifying to see learners appear in on Monday actually shy, but by Friday be actively collaborating, producing jokes with the mentors, and becoming truly psyched about STEM.”

To look into the prolonged-term impacts of the program, he also served kick-get started a undertaking that followed up with DynaMIT alumni, some of whom have now graduated from college. Zhang claims: “We were being joyful to see that 80-90 p.c of DynaMIT alumni enjoyed the plan, score it four or five out of 5, and near to 70 p.c of them stated that DynaMIT experienced a really positive effects on their trajectory towards a occupation in STEM.”

Zhang has also served as president of the MIT Pre-healthcare Culture, with the plans of fostering an encouraging setting for premed undergraduates, and furnishing steerage and assets to initial- and second-12 months learners continue to undecided about the premed route. To reach these objectives, he pioneered an MIT-hosted mixer with the premedical societies of other Boston colleges, such as Wellesley Higher education, Boston University, Tufts College, and Harvard University. At the mixer, pupils were being capable to community with every single other and pay attention to visitor speakers from the unique universities converse about their ordeals in medication. He also commenced a “big/little” initiative that paired 3rd- and fourth-calendar year mentors with initially- and next-12 months students.

Offering new chance and hope

The wealth of functions Zhang has participated in at MIT has encouraged his decisions for the long run. Immediately after graduation, he programs to get a hole yr and perform as a research technician in pediatric oncology prior to making use of to MD/PhD packages.

On the mentorship side, he’s at this time operating to establish a nonprofit firm known as Foreseeable future African Scientist with his former Ugandan roommate, Martin Lubowa, whom he achieved at a review abroad software in the course of MIT’s Independent Activities Period of time in 2020. The corporation will teach high schoolers in Africa expert abilities and expose them to different STEM matters — a venture Zhang programs to operate on submit-MIT and into the prolonged phrase.

Finally, he hopes to direct his have lab at the intersection of CRISPR-Cas9 technologies and cancer biology, and to provide as a mentor to future generations of researchers and doctors.

As he places it: “All of the ordeals I have had so significantly have solidified my purpose of conducting study that impacts sufferers, specifically youthful ones. Remaining capable to present new prospect and hope to patients struggling from late-phase metastatic diseases with no recent cures is what conjures up me every working day.”