Posted By: HGG Advances
Each month, the editors of Human Genetics and Genomics Advances interview researchers who have published work in the journal. This month, we check in with Adelaide Tovar (BlueSky: @adel-aide.bsky.social) to discuss her paper “Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions.“
HGGA: What motivated you to start working on this project?
AT: With my PhD training in statistical genetics and genomics, I was eager to complement my discovery-focused training with functional genomics approaches during my postdoc. During this stage of my training, I’ve focused on using massively parallel reporter assays (MPRAs), which are used to measure regulatory activity across a panel of candidate regulatory elements. To get up to speed on both building MPRA libraries and performing downstream analyses, I took on this project from a previous postdoc. It proved to be an effective way to build a solid foundation in the method while also yielding some very cool findings that have influenced subsequent projects.
HGGA: What about this paper/project most excites you?
AT: In brief, our paper shows that MPRA design (position of fragment relative to the promoter and the choice of promoter) can alter enhancer activity across the same set of fragments. I’m most excited by our observation that using a tissue-specific promoter in MPRAs, rather than a generic housekeeping promoter, improves detection of enhancer activity from tissue-specific regulatory elements. This quite simple design change has a meaningful impact on our downstream findings.
HGGA: What do you hope the impact of this work will be for the human genetics community?
AT: My hope is that this work will encourage other researchers to consider the promoters they use in MPRAs and how they might affect the interpretation of variant effects. For those working in specific disease areas, adopting tissue-specific promoters might yield sharper atlases of noncoding variant effects and better prioritization of causal variants for follow-up experiments.
HGGA: What are some of the biggest challenges you’ve faced as a young scientist?
AT: One challenge has been the relative scarcity of mentors and visible role models in senior positions who come from similar backgrounds to mine. That kind of representation matters more than I appreciated early in my training, both for navigating the practical realities of pursuing an academic career and for just seeing what’s possible. The second is the competitive nature of academic science, which, in many ways, is an understandable reflection of resource constraints. I tend to be more energized by collaboration and collective success, and I have been fortunate to have mentors and colleagues who share that view and make the work genuinely fun.
HGGA: And for fun, what is one of the most fascinating things in genetics you’ve learned about in the past year or so?
AT: I’m a self-professed cat lady, so I really enjoyed a pair of papers published in Current Biology last year describing the genetics of orange coat color (PMIDs 40378840 and 40378841). Calico and tortoiseshell coat patterns in female cats are classic examples of X-inactivation and mosaicism, but the specific gene driving coat color had never been identified. Both groups convergently discovered a 5.1 kb deletion between two alternative transcription start sites for the gene ARHGAP36. There is an ultraconserved, putative regulatory element in this region that, when lost, causes ectopic expression of ARHGAP36 in melanocytes, which shifts their pigment production from brown/black to orange. As someone who loves gene regulation, it’s exciting to see an example of a phenotypic change caused by the loss of a regulatory element instead of altered protein function.
Adelaide Tovar, PhD, is a postdoctoral fellow in the Department of Computational Medicine & Bioinformatics at the University of Michigan Medical School.