In book that looks more worn out than

In pursuit of tackling human diseases from the collision by innovative technology advancement, I would like to
introduce myself as a curious and tenacious adventurer for the Yale Biomedical Engineering program.
Among the life sciences textbooks on my cramped bookshelf, there is one book that looks more worn out than
the others. I have kept it since high school. The book is titled ” Genius or Maniac?” It is a collection of stories
about psychiatric patients that unveil the bewildering unexplored areas of human nature. This is the book that
elicited my interest in life sciences, and has been a reminder for me to take one more adventure.
My first taste of hands-on scientific research dated back to my freshman year in the International Genetically
Engineered Machine (iGEM) competition. I wasn’t afraid to take the road “less traveled by” – any road was
“never traveled by” for me at that time! The result, being selected as one main team member over a pool of
outstanding junior, senior and even graduate students, motivated me so much and made me thankful to this
try. Heartbroken by the severe drug resistance caused by antibiotic abuse in China, our team decided to tackle
on accurate and sensitive detection machine to catch trace antibiotic concentration. As one freshmen student
in the group, I got excited by smallest triumphs like having managed to grow our engineered E. coli and seeing
it amplify trace signals of antibiotics. Looking back, this kind of “go straight into the unknown” way not only
push me closely to research, but introduced the specific and magic genetic engineering field to sense me the
power of bioengineering in biomedical science for the first time.
During our iGEM trip, Professor Jiangning Zhou shared with us about the introduction of novel optogenetic
method, another application of genetic modification, to his laboratory. His ideas sparked my curiosity: What is
the limitation of traditional methods in a narrow field spurs this method update? As a specialist in Alzheimer’s
disease, Professor Zhou kindly invited me to his lab to explore for the answer myself. After researching
literature extensively and engaging discussion with senior graduate students in the lab, I realized the
complexity of psychiatric diseases, most of which have hundreds or even thousands of genes that are
essentially culpable. Compared with traditional gene-targeting methods, optogentic imports a dynamic image
encouraging us to shed light on the interaction between specific genes and neurons. Thus, figuring out how
these criminals react collectively at the entire neural circuity could be an attractive alternative to gain a more
complete picture of this system. Inspired, I decided to study the role of corticotropin-releasing hormone
neurons in the hypothalamus’ paraventricular nucleus in the fear condition independently. However, that was
a challenging year with a heavy course load and many tough experimental moments, for example, only being
able to make full use of lunch breaks and late nights to run experiments restricted my research process, the
blindness until imaging part weakened the efficiency as well as increased the risk of murdering time, and every
unobtrusive factor like the variance between personalities of every mouse, the discordance of circadian clock
between human and mice or the fluctuation of laser intensity brought about the instability of mouse model
and not tenable enough behavior results. Smiles and tears always come together. The apparently lower
freezing behavior after laser activation reveals the significance of corticotropin-releasing hormone in
emotional expression and the possible existence of up- or down-stream pathway. To conclude, those
difficulties developed me a more dialectical thinking of the relationship between technology with research
while at the same time the meaningful results gradually lightened my career pursuit: to generate technology
innovation to approach the tough questions from different angles and at the systems level.
The discovery of the specific goal for my future career plan came with another realization. The US is the place
where the best universities and the most frequent communication are, with more opportunities to stimulate
new ideas and foster new collaborations across disciplines. If I wish to make best progress, I need to earn my  place in one of the best universities. That realization was like a shot of adrenaline, pushing me to work even
harder for a sharp increase in my major GPA to 3.80 within the junior year.
The hard work earned me a summer research intern position at Yale University, where I fortunately get the
chance to stay at Professor Rong Fan’s lab by proactively reaching out for him. After two months in his
laboratory working on novel single-cell RNA-seq technology and informatics, I was invited to stay at Yale to
finish my undergraduate thesis under his supervision, excited and honored. Serving as an accurate radar, the
single-cell technology shocked me as an incredible tool to decipher and highlight the hidden mechanism in
pathogenesis associated with cell-cell heterogeneity. For example, when in the collaboration with a
postdoctoral associate from Professor Qin Yan’s lab at Yale Pathology, I obtained the clear visualization of
complex tumor microenvironment from experimental data. On the basis of it, we would next work on validating
previous hypotheses about tumor marker genes thus enabling more accurate targeting. By performing headto-head
gene and protein comparison within single-cell transcriptome and proteomics, I helped demonstrate
one of lab previous work in protein secretion heterogeneity and dynamic immune responses. Furthermore, I
was confident about my identification of the most aggressive subsets in human brain tumor glioblastoma
would contribute to clinical treatment during the cooperation with one graduate student in Fan lab. While
there is no road where everything going smoothly. Prof. Fan and I ran into a question later, the status of cell
samples could be totally and secretly turned over during the long-distance transportation. What is worse, any
extreme atmosphere would cause irreversible damage. Learned from the single-cell concept, which has shifted
our attention from population-level analysis to the measurement of individual cells, we decided to build a
sequencing platform for single-nucleus and set it as my thesis project. Adopting the user-friendly simplification
from single-cell platform and bolding cutting the lysis step are now making the establishment of nucleus
platform different from cellular one but move smooth. The success in the first pilot of technology improvement
makes me now one hundred percent sure of my potential in the field of Biomedical Engineering and
determined to run directly to advance my research training as a Ph.D.
It is reasonable to believe that Yale Biomedical Engineering program and I are great matches for each other. I
am extremely excited about the fact that Yale has three campuses densely populated with state-of-the-art
research programs and facilities makes it very convenient to communicate with different people from diverse
backgrounds, either Biomedical Engineering or Yale School of Medicine, which accelerate the translation of
basic research results and technical breakthrough into applications in clinical settings. Take single-cell platform
as an example, if I could luckily enough to continue staying in the Professor Fan’s lab to learn more in
engineering platforms and single cell analysis, thus build more platforms such as sequencing several omics
together at one time. We can extract more biomedical results by collaborating or communicating with some
professors from Yale School of Medicine.
Inspired by my short stay at Yale so far that has significantly broadened my scope of knowledge and expertise
in cutting-edge biomedical science, I would really appreciate the opportunity to join the Yale BME program as
a graduate student. There is undeniable that Yale is the best place to achieve my career goal: to be an
independent scientist in biomedical science and engineering research. I’m ready for next adventure at Yale.
Hope it is also ready for me.


I'm Harold!

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