Capstone Showcase: Xiaotian Liao

The development of CRISPR-dCas9 Activation gene editing technology as a form of Hemophilia A treatment

Xiaotian Liao is driven by the desire to help those around her. She came to Minerva to study in diverse locations across the globe and to conduct pioneering research in the medical field, specifically in genetic diseases. Throughout her time at Minerva, Xiaotian has challenged herself to pursue new opportunities that would enable her to improve her professional and personal skills. Her hard work, determination, and experimentation have helped her accomplish these goals. 

For her Capstone Project, Xiaotian presented both the data from research on hemophilia she conducted at the Harvard Stem Cell Institute (HSCI) and completed several follow-up investigations to discover alternative methods to improve CRISPR editing outcomes. The project required her to use skills developed in her two majors, Natural Sciences and Computational Sciences.  But joining a prestigious lab as an undergraduate student and researching life-saving cures was not an overnight achievement. Since her first year at Minerva, Xiaotian has consistently challenged herself, diving into new disciplines, pursuing intensive research positions, and gracefully excelling in her demanding academic courses.

In her first year, Xiaotian was surprised to find that she enjoyed Formal Analyses, a Computational Sciences course focused on learning inductive logic and algorithmic thinking, more than she originally thought. 

“I don’t think I would have taken coding classes if I had not come to Minerva,” she explains. “But I really enjoyed the problem-solving aspect of programming and appreciated the support from the faculty when I was first introduced to the computational sciences side of things.” The guidance she received from her professors gave her the confidence to continue to study machine learning and explore the role of computer science in medicine.

To gain further exposure, the summer after her first year, Xiaotian took a specialized data science course at General Assembly in San Francisco. There, she applied machine learning models to hospital readmission rates to identify and predict which sets of patient populations were most susceptible to readmission. This analysis would enable hospitals to better provide preventative care. Similar to her classwork at Minerva, Xiaotian valued the program’s format of connecting academics to a complex, real world issue. 

“I gained a great deal from [the program] as I learned how to frame complex problems in a way that can be further dissected, how to apply and develop appropriate statistical models to solve such problems, and how to communicate my findings with others in an effective manner.”

In addition to the data science course that summer, Xiaotian also interned with the marketing team at Minerva. Even though experience in communications and public relations are rarely necessary in traditional medical and research career paths, she sought to improve in an atypical manner. She saw the long-term value of strengthening her English language skills to be able to effectively communicate in both English and Mandarin, two of the most spoken languages in the world.

After her second year, Xiaotian applied for the Bioinformatic Summer Scholars program at the Novartis Institute of Biomedical Research, a research division of Novartis, an international healthcare and pharmaceutical company. She believes that her coding abilities and experience in analytical problem-solving, gained from her Formal Analyses class and summer data science program, made her a compelling and successful applicant for this highly competitive internship.

At Novartis, Xiaotian was thrilled to be working in a professional research setting and joined the bioinformatics team in the oncology department. Working on two RNA data analysis projects, she applied statistical models to RNA data from human tissue samples to create a more efficient predictive model for sample quality. A highlight of her internship was her ability to work with Cluster, a high-performance computer, for the first time. This exposure to big data and cloud computing ignited a passion for using large-scale genomic data to better understand complex biological phenomena, such as human diseases and genetic circuits.

In addition to gaining valuable research experience at Novartis, Xiaotian also continued to practice her communication skills. When presenting her project progress and results, she altered her pitch to best fit the audience. For example, when presenting to those without a background in bioinformatics, she made a point to clearly explain the technical jargon and terminology to avoid confusion before detailing her hypothesis. For her peers already versed in bioinformatics, she was able to skip the initial explanation and instead focus on her implementation and projected next steps.

While in Seoul, the fourth global rotation city, Xiaotian joined an immunology research project at Hanyang University. There she continued to learn laboratory techniques and computational work, but also embraced the cultural context.

Xiaotian chose Minerva, a world-traveling, liberal arts college, not just to complete the course requirements for medical school applications but to also build her understanding of the different medical systems, communities, and practices in each location. By viewing medicine as an interconnected global system, rather than an isolated field, she expanded her own career opportunities and increased her ability to empathize with future patients from different backgrounds than her own.

Living immersively in San Francisco, Berlin, Buenos Aires, Seoul, Hyderabad, and London, as well as a summer Boston, and being supported by a vastly diverse set of classmates, are some of the aspects Xiaotian appreciates most about Minerva. 

“I would say that after [being at Minerva], I’ve definitely become better at trying to be as empathetic as possible when it comes to people or concepts that I don’t initially understand. I feel that empathy and understanding are necessary for people who are in a global environment.”

Prior to her fourth year, after being accepted to several laboratory internships, Xiaotian chose to join the research team at HSCI in Boston, Massachusetts. The team was working to discover a new treatment for Hemophilia, a blood-clotting disease. This pivotal and innovative research was very personal to Xiaotian, because her father is afflicted by a similar disease: myeloproliferative neoplasm. 

Using the gene-editing tool CRISPR to test hematopoietic stem cells, which are responsible for blood production, the team activated blood-clotting genes in hemophilia patients, hypothesizing that such patients do not express a blood-clotting gene and, if that gene could be activated, their research could contribute to a cure. 

While CRISPR research normally seeks to “turn off” maladaptive gene expressions, like those for cystic fibrosis, Xiaotian’s research utilized a modified CRISPR to attempt to “turn on” gene expressions in hemophilia patients. While the research is ongoing, during her internship, Xiaotian was able to successfully activate the gene in human primary cells, with further research underway to determine whether the activation was strong enough to produce corresponding blood-clotting proteins

Her work with the HSCI research team became the focus of her Capstone Project as well. For that, Xiaotian worked closely with Minerva Professor Abha Ahuja. 

“Given what a self-motivated person Xiaotian is, I was more of a sounding board for her. She would come up with the ideas and say, ‘I’m interested in these seven different things!’ and I helped her navigate the constraints,” Professor Ahuja explains.

In addition to the already demanding Capstone requirements, together, Professor Ahuja and Xiaotian set out to produce a work that could be publication quality — one with a high level of detail and sophistication of a scientist.

“The goal wasn’t to just write a Capstone. It was to write something that others in her field would respect and think of Xiaotian as a peer. And she was up to that challenge.”

In addition to her Capstone research, Xiaotian also led a group in London called the NHS Guild—an acronym for the comical “Nerds Helping Students.” The group connected Minerva students who shared similar career interests, with relevant professionals in the city.

With NHS, Xiaotian coordinated informational sessions with professionals working across multiple fields from medical administration, the nonprofit sector, and start-ups, to provide her classmates with a more holistic understanding of the healthcare ecosystem. One partner that stood out to Xiaotian worked as both a physician and entrepreneur in the biotechnology industry. 

“I got to realize how multifaceted medicine is. It’s not just a science or [body of] knowledge. It’s also about communication and public policy. I’m really glad I got to realize and understand that [through the NHS Guild.]”

For the first part of her Capstone Project, Xiaotian summarized her HSCI laboratory experience, compiled a literature review of the research, and analyzed the results. In her analysis, she tested the guide RNA (gRNA), which is a specific RNA sequence that recognizes the target DNA region of interest, to confirm that the CRISPR technology was working in the right cellular location and to gauge the effectiveness of the treatment. 

The second part of the Capstone directs students to explore their chosen topic through an undefined creative project. For this, Xiaotian completed various types of investigations to highlight potential ways to improve CRISPR editing outcomes in primary human blood cells. These included epigenomic studies, which look at the chemical compounds in the gene expression, and a motif study to find the repeated sequence of patterns in the genome linked to a specific function. 

In praise of Xiaotian, Professor Ahuja explains, “I was very careful about the students I took on [to supervise], because it was important for me to work with students who were not just academically strong or who would do a good Capstone but I wanted to work with someone, like Xiaotian, who was also kind and nice to work with … I can’t think of a better way to describe her.”

During Manifest, the culmination of the Minerva academic journey, Xiaotian presented her work to her classmates, Professor Abha Ahuja, and Professor Trisha Stan. While she had presented her work before, to colleagues in her lab and peers in her field, it was a new experience presenting her work to the Minerva community, a group that varied greatly in knowledge of bioengineering. She had to ensure that her work material could be applicable and understandable by others.

“It was crucial that I explain my work not only to people in my industry, but to those outside of it, as well. I hope to become a physician someday, so I’ll need to be able to communicate the nature of science clearly to anyone.”

During Xiaotian’s Capstone defense, Professor Ahuja and Professor Stan challenged her even further than required. Stepping away from the minutiae and specificity of her project, they asked Xiaotian to explain the “big picture-impact” of her research and how it related to the entirety of the bioengineering world. Though it forced her to step back from the focus of her project, she responded with considerable poise and thoughtfulness, as usual.

“In her first year, I knew that if I called on her, she would say something thoughtful. Even if she didn’t know the answer, which happened very rarely, she was always very thoughtful and sincere. She would put in her best effort,” Professor Ahuja recounts. “We all knew about her academic abilities, but her growth in confidence and her willingness to put herself out there is something I really noticed.”

After graduating from Minerva, Xiaotian returned to Boston to work at the Boston Children’s Hospital. There she is continuing research at the Harvard Stem Cell Institute, testing for genetic variance of a population to phenotypes for myeloproliferative neoplasm, the blood cancer disease her father is fighting. Patients with the disease produce an excessive amount of blood cells, which can lead to clotting in the blood vessels with potentially dangerous phenotypes, such as strokes or heart attacks. Specifically, she is seeking to better understand the genetic mechanism of myeloproliferative neoplasm, through CRISPR perturbations of genetic variants — alterations in the DNA.

Minerva isn’t a forgotten experience, over the past several months from graduation, Xiaotian has reflected on her time at Minerva, and how elements can be intertwined into her post-graduate life.

“While I’m here [in Boston], I’m trying to not get too tied up in the work itself, and trying to think of ways I can continue the Minerva experience. I’ve been making up my own Location Based Assignments and finding my own Civic Partners, it’s been pretty fun.”

Throughout her time at Minerva, Xiaotian has explored countless new opportunities presented to her and transformed the challenges as a way to develop herself as a future research physician and an incredible human being. Whether it was exploring a new interest in computer science, joining research teams in new countries, – even applying to attend Minerva in the first place — Xiaotian’s accomplishments and success are a clear result of her hard work, vulnerability, motivation, and intellect. And her future looks just as bright.