Quick Q&A with NCBI’s Gene Regulation Group

We were curious.

What is going on in Ivan Ovcharenko’s group in NCBI’s Computational Biology Branch?

On the sixth floor of NLM’s Lister Hill Center, Dr. Ivan Ovcharenko and his team are deciphering what he calls the “second language” of the human genome.

He explains, “The primary language of genomes—which represents the genetic code of proteins and is used by every cell to encode all necessary proteins—was discovered in the 1960s by Marshall Nirenberg and Heinrich Matthaei. Forty years later, the international effort to sequence the human genome resulted in a puzzling observation that less than three percent of the human genome encrypts the genetic code of proteins and is used for protein encoding.”

In this Quick Q&A, these scientists not only tell us more about what’s happening on the sixth floor, they tell us about their backgrounds. We bet you’re as curious as we were.

Read more Quick Q&As with NCBI scientists.

Quick Q&A with Ovcharenko, Flores, and Huang
Question Ivan Ovcharenko, PhD Mario Flores, PhD Di Huang, PhD
headshot of Ivan Ovcharenko casual headshot of Mario Flores casual headshot of Di Huang
In lay terms, what is the focus of your NLM research? My group at NCBI is interested in deciphering the “second language” of the human genome. The vast landscape of the human genome hosts elements that orchestrate the dynamics of proteins in every human cell, establishes cell identity, and safeguards the defense mechanisms. These elements, known as gene regulatory elements, are encrypted in a different genomic language known as the second language of genomes. As this second language of genomes remains largely unknown, we are working on developing novel artificial intelligence methods to understand the genomic encryption of gene regulatory elements and use it to map the location of these elements in the human genome. The focus of my project is the study of genomic regulatory regions (regions that do not codify proteins but that have some control on the transcription of genes) that have changed their function during the evolution of mammals. I am interested in understanding the general mechanisms that control cell identity, which have an effect on development and disease. I focus on gene regulation. I develop and apply statistic models and data mining algorithms to reveal gene regulatory mechanisms underlying various complicated biological processes, such as tissue development and carcinogenesis.
Why is it significant, in your opinion? It is difficult to underestimate the role of gene regulatory elements in cellular biology given their crucial role in controlling the fate and function of every single cell in our body. As more human genomes become sequenced and analyzed for disease-associated mutations, we are learning that mutations of gene regulatory elements are associated with a wide range of human diseases, disorders, and traits ranging from cancer and heart disease to body mass index and eye pigmentation. To accurately quantify disease susceptibility, advance personal medicine, and design novel drugs targeting gene regulatory mutations in the human genome, we first ought to learn the encryption of these elements and understand how changes in their genomic sequence impact their biological activity. It has been shown that variants in regulatory regions are associated with many diseases, and it is very important to expand our understanding of the molecular players and mechanisms involved. In the central dogma of biology, gene transcription is a key stage of gene expression. The regulation and control of gene transcription in many biological systems remain elusive. The high-throughput techniques generate huge amount of nucleotide-base-revolution data. Handling and analyzing these data are challenging, but will deepen our understanding of complex biological systems on a molecular level.
What or who inspired you to pursue your career? I attribute my passion for science to the endless discussions with my father about his research work on “organic magnets” and to the dedication of my incredible high school physics teacher, Vladimir Shelest. I’m indebted to Dr. Edward Rubin for his guidance and unconditional support during my transition to computational biology. At the end of my Master’s in applied mathematics, I had a conversation with a computational biologist Dr. Yufei Huang that inspired me to pursue a PhD in this very interesting field. I come from a family of engineers. My parents gave first inspiration and encouragement on science and engineering.
How did you get started in your career? After obtaining a graduate degree in theoretical physics and completing a postdoctoral fellowship in 2000, I finally realized I’m most excited about computational biology. I spent seven years studying the human genome at the Lawrence Berkeley and Lawrence Livermore National Laboratories prior to joining the Computational Biology Branch of NCBI as a tenure-track investigator in 2007. I started by attending a summer seminar at the Greehey Children Cancer Research Institute in San Antonio, Texas, that introduced me to the study of data generated by the Next-Gen DNA sequencers. I learned computer science in college and graduate school, focusing on analyzing and mining large data sets during my PhD study. Upon graduation, I applied my data mining knowledge to biological data, since the biological topics are intriguing and biological data are challenging to me.
What really gets you jazzed about science and research? Our ability to improve human life by learning the secrets of our genomes. I believe curiosity and the nightly conversations with my father, who was a physics teacher. Broadly speaking, science and research amaze me very often in my daily life—from my own experience in clinical trials to the explorations (reported in the media) of our external world and the human body.
If you weren’t doing this work, what other profession might you have pursued? Astrophysics. I’d love to study Hawking radiation. I probably would be guiding a group of people to the top of a local mountain in my home country. Maybe a teacher.
Tell us something surprising about yourself. I grew up in a small scientific town hidden in the woods of Siberia, a place with several dozen research institutes, a medical academy, a university, and…nothing else, creating an unusual environment where almost everyone is a scientist. Growing up, you know you will be a scientist, too. The only choice you have is the scientific discipline that excites you the most. I am planning to visit the Himalayas next year. How hard and sophisticated English is as a language. I’ve learned English for 30 years, and have stayed in the USA nearly 10 years. I fall short now and then when it comes to my English skills.
Quick Q&A with Li, Malin, and Song
Question Shan Li, PhD Justin Malin, PhD Wei Song, PhD
casual headshot of Shan Li casual headshot of Justin Malin casual headshot of Wei Song
In lay terms, what is the focus of your NLM research? My study focuses mainly on identifying potential causal variations that affect gene regulation or even lead to common disease and genotype divergence in human population. I am also interested in studying the conservation and exaptation of regulatory mechanisms during evolution, especially in heart and brain tissue. We are looking at a large set of gene switches (“enhancers”) that have long been assumed to behave near-identically in very different tissues of the body, but that, on closer inspection, do not. Focus on the mechanisms of coordinated gene regulation established by a panel of enhancers. Address differences between regulatory architectures consisting of singular and multiple enhancers.
Why is it significant, in your opinion? My study would contribute to accurate identification of disease-causal mutations in the human and other genomes. I hope it would narrow the searching scope of disease-related mutations for biomedical research and drug design. This work potentially could provide fresh insight into a long-standing question: How does our DNA, which is effectively identical across all our cells, code for such different tissue types? In addition, we hope to shed light on the evolutionary processes underlying the creation of gene switches in general. The latest research shows most of the genetic diseases are caused by the mutations happening in non-coding regions of our genome, including protein binding enhancer sites.
What or who inspired you to pursue your career? When I was in college majoring in mathematics, a professor in my department, Dr. Guojun Li, started his research in bioinformatics and collaborated a lot with a research team at the University of Georgia. He inspired me to translate my expertise in the bioinformatics area, and he recommended that I pursue a PhD degree in bioinformatics and genomics in the US. My career path has hardly been direct, so it’s tough to pinpoint a single inflection point. A great class on biological networks in grad school was definitely inspirational. Continuous interests in exploring the truth of science and developing possible drugs and cures for diseases.
How did you get started in your career? After a couple of years’ study of biological science and computations, I started doing research on the gene regulation in bacteria, which also paved the way for the study of gene regulation in humans. A mid-life career change. When I was studying engineering in college, I didn’t know there were people working at the interface of computation and life sciences. Bioinformatics, in particular, was still years off in the future. I am always interested in biology and got further training in college.
What really gets you jazzed about science and research? Science and research always push me to think and learn. Some of the findings and observations in my study made me really excited, although I know they would make tiny contributions for biological science. Chasing down the trail of discovery, and the prospect of contributing to a body of useful knowledge that will outlast my own body. And the interviews. Come with the problems, solve them, and apply the solution to practical cases, such as disease.
If you weren’t doing this work, what other profession might you have pursued? I might find a job related to finance, or I would pursue a career in broadcast media in China. Something very similar. At this point in my life, I know what I want. Maybe work in the IT industry.
Tell us something surprising about yourself. I am still good at singing English songs. I have a dial phone in my bedroom. My best record is eight three-pointers in 10 shots.

Contributor Allison Fisher, NLM public affairs specialist

2 thoughts on “Quick Q&A with NCBI’s Gene Regulation Group

  1. Hi Cynthia, Thanks so much for taking time to let us know that you enjoy these “biosketches.” We enjoy researching and writing them! Please keep checking back. We have more profiles to share.

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