Dive deep into genetic | Professor Joohyun Lee’s hunt for epigenetic regulations

Professor Joohyun Lee was born in Seoul, South Korea. After earning a master’s degree at POSTECH in South Korea, he moved to the US for a PhD degree at Dartmouth College. After this, he joined a postdoc program at the University of Wisconsin-Madison, and then he started his teaching career at Amherst College, one of the major Liberal Arts colleges in the US.

Recently, he has moved to Duke Kunshan University for his next stage of teaching and research careers. At DKU he is mainly working on epigenetic regulation using model plants such as Arabidopsis thaliana.

“Memories” across generations?

The debate over whether a trait of an organism can be passed down to the next generation has long been a research focus for scientists studying genetics. To provide context, Prof Lee referenced the classical debate between the Soviet Union genetic agronomist Trofim Lysenko and genetic scientist Nikolai Vavilov.

As Lysenko studied vernalization – a “shock-therapy” that exposed the plant into cold temperature and “tricked the plant to think that winter season has already passed” to boost earlier germination, or rapid flowering. Lysenko explained such phenomenon using a Lamarckism interpretation of the ‘inheritance of acquired characteristics’, which, now widely rejected⁠, suggests that individuals have the ability to modify their features during their lifetime and pass them down to their offspring. Lysenko falsely claimed that a one-time vernalization treatment would be sufficient and yield many generations of seeds that would spend less time before flowering, and therefore could boost agricultural yield for the Soviet Union. 

On the contrary, Vavilov had defended the Mendelian theory which demonstrated the mechanism of how genes are passed down from generation to generation.

Prof Lee added that while Lysenko is a bioscientist, he was also a prominent figure in the political circle. Although his hypothesis is completely wrong, his political role had helped his “finding” to evolve into the acting policy in the Soviet Union. Eventually, his failure to understand how genetics works, and his fake promise of the higher-yield seeds from the one-time vernalization had only exacerbated the poverty and famine that haunted the Soviet Union around the 1920s.

While the historical debate in the Soviet Union ended in the confirmation of Mendelian genetic theory, scientists also raised examples from more observations. Occasionally, mothers that have bad living habits (e.g. smoking, consuming alcohol, weed or drugs) will have some influence over the genetic matter passed to the next generation through a process called DNA methylation, which happens to cytosine that is part of the DNA strand. In fact, as Prof Lee stated, this is why epigenetics is so important. Epigenetics will strengthen understanding the flow and regulation over how genetic materials are switched and altered, and further affect gene expression and protein quantity.

What is Epigenetics?

Epigenetics might be an unfamiliar discipline to most of the audience, so Prof Lee provided some introductory knowledge about this field.

People who went through the general biology class would be familiar with DNA mutations. These changes in DNA are usually irreversible. However, it is possible to add chemical modifications to the DNA sequence to alter gene expression and change protein quantities. This is called epigenetics modification, which is usually reversible.

One of the well known examples is called Mitotic and Meiotic Inheritance. In Mitotic inheritance, gene expression alterations are preserved as genes are copied from cell to cell. In Meiotic inheritance, the alterations are maintained from one generation to the next.

Prof Lee has been diving deep in epigenetics for many years. In his post-doc research, he focused on the transferring signaling mechanism outside of the nucleus that controls epigenetics regulation. At DKU, Prof Lee is exploring epigenetic regulation using plants such as Arabidopsis. He explained that to better understand epigenetic regulation, researchers need to obtain organisms that have viable epigenetic mutations. However, epigenetic mutations in higher eukaryotes are often lethal or causing fertility issues, preventing scientists from further research using the model organisms such as mammals or fruit fly. However, plants can typically survive epigenetic mutations, and the regulation of epigenetic mechanisms is highly conserved across higher eukaryotes due to its very recent evolution. Prof Lee’s main research focus is on utilizing plants, which can be applied to a wide range of higher eukaryotes, including humans.

And because epigenetic regulation has only evolved recently, it is highly conserved among organisms: the regulator, regulation pathways and even complex components could be quite similar between plants and mammals, the mechanism learned from plant experiments would also cast light on the understanding of the epigenetics regulation in animals and even humans.

As Prof Lee mentioned, their research team has already applied knowledge learned from researching epigenetic regulations into drug research, and successfully created a new cancer drug that has been approved by FDA and is currently undergoing clinical research.

Monitoring DNA Methylome

One of Prof Lee’s major research interests is the irreversible epigenetic change. It is possible that some of the specific environmental conditions will switch some of the DNA methylations, and then those DNA methylation changes will influence the gene expressions for at least many generations.

Since the observation will span between cells and across generations of a species, this would not be a short-term effort. Prof Lee said he also has a plan to monitor methylomes. which means analyzing methylation status in the whole genome, and the analysis could also expand into monitoring transcriptome with whole genome RNA sequencing, methylome with whole genome methylation status, histone modification with whole genome CHIP sequencing.

Right now, Prof Lee is working on preparing the type of the experiments that would cover these monitoring tasks, which may reveal what kind of methylation could remain a larger count of generations after the environmental treatment.

Life at Duke Kunshan University

Being a college professor at DKU, Prof Lee mentioned that he is actually passionate about teaching. Currently Prof Lee is teaching 100-level biology classes such as introductory biology. His research lab also hosted more than a dozen undergrads who are working on different individual and team projects.

Prof Lee spends about 30~40% of his time mentoring and teaching students. He mentioned that his email is always full, and he spends quite a lot of time replying back to students, hosting office hours and meeting students individually to hear opinions about the course and the lab. Under Prof Lee’s guidance, most of his previous Signature Work students have successfully gained admission to prestigious Ph.D. programs. For example, three students were admitted to Duke University, one student was admitted to the University of Michigan Ann Arbor, and another student was admitted to Tulane University. Additionally, they also successfully secured full tuition and full stipend for living costs. When asked about what are the qualities he expects from prospective students, he says he usually is looking for students who have a higher level of responsibilities. Experiments in the lab may often fail, and he could see that students with higher levels of responsibilities could easily recover from failure and have the endurance to try again, and this will eventually lead to their success in pursuing the research career.

Interviewer & writer: Liansai Dong