Inside HGG Advances: A Chat with Gautam Pandey

Posted By: HGG Advances

Each month, the editors of Human Genetics and Genomics Advances interview an early-career researcher who has published work in the journal. This month we check in with Gautam Pandey to discuss his paper “Liver regulatory mechanisms of noncoding variants at lipid and metabolic trait loci.”

Gautam Pandey, PhD is a postdoctoral fellow in the Department of Genetics at the University of North Carolina-Chapel Hill.
Gautam Pandey, PhD is a postdoctoral fellow in the Department of Genetics at the University of North Carolina-Chapel Hill.

HGGA: What motivated you to start working on this project?

GP: Non-alcoholic fatty liver disease is a silent epidemic, and 25% of Americans are affected by it. There are currently not any medications approved for this disease. This is partly because we poorly understand the genetic mechanisms associated with this disease. Although GWAS have discovered many loci associated with fatty liver or lipid disorders, they mostly lack functional validation. That said, the functional validation of such loci is even more difficult when they are in non-coding regions. Our computational colleagues in the lab generated a huge list of candidate liver regulatory elements by mapping chromatin accessibility using liver tissue samples.  The motivation really comes from there when I started working with these regulatory elements and discovered that there could be many potential targets which should be functionally validated for their biological effects.

HGGA: What about this paper/project most excites you?

GP: I am absolutely fascinated by the way non-coding variants can alter gene expression and function. I have learned so much about them in the past year or so: the way they can change the biology of a gene or alter the transcription factor binding sites in context-based assays. Even more exciting is that some of these variants are so distant from their target genes that they can even affect a gene more than 1 MB away. I will be thrilled to discover more about these non-coding variants in future.

HGGA: What do you hope is the impact of this work on the human genetics community?

GP: This paper provides a framework to identify a functional non-coding variant-gene pair that can play a significant role in regulating lipid biology of the liver. What is more interesting is that the target genes for some of these variants, which are predicted by computational methods, can be functionally validated using advanced epigenome editing methods like CRIPSR-interference. This approach will unfold several potential targets to treat non-alcoholic fatty-liver disease.

HGGA: What are some of the biggest challenges you’ve faced as a young scientist?

GP: As a young scientist, I always become very enthusiastic about my new projects and research; sometimes failure in experiments or projects becomes a hard pill to swallow. I must say, however, that one should learn when to move on with your experiments if they are not working: this is one of the most difficult decisions to make in science. Also, I feel like apart from doing research, there is always a challenge to find more time to learn new skills and to focus on self-development which can propel one’s research excellence.

HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?

GP: The most fascinating thing I have learned is to decipher the complex nature of chromatin regulation by epigenome editing. In the last year or so I have learned about CRIPSR-interference and -activation, and how these methods can be used to target chromatin regulatory elements to alter gene expression and function.

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