Yingqun Huang, MD, PhD

Dr. Huang’s research centers on the mechanistic understanding of endocrine disorders including diabetes and infertility, in addition to reproductive tract tumors. In the past 7 years studies from her laboratory have demonstrated that long noncoding RNAs (lncRNAs) play an important role in human health and disease and could constitute a novel class of RNA therapeutics for uterine fibroids, ovarian and endometrial cancers, and diabetes. Her significant contributions in the fields are highlighted by multiple publications in high impact journals, including Molecular Cell, Nature Communications, EMBO Molecular Medicine, PNAS, Nucleic Acids Research, Cell Reports, Diabetes, and Oncogene. Her current research focus includes mechanistic dissection of H19 lncRNA and TET proteins (a new class of DNA demethylases) in epigenetic regulation of gene expression, with the ultimate goal of discovering new molecular signatures and pathways for preventing and treating disorders such as diabetes and infertility.

Specialized Terms: Noncoding RNA; Epigenetics; Metabolism; Diabetes; cancer

My passion for scientific discovery and “thinking outside the box” have positioned me perfectly for major contributions to the mission of YSM. During graduate and postdoctoral work, I was interested in the rules and mechanisms governing the transport of mRNAs from the nucleus to the cytoplasm. I showed for the first time that proper 3’-end formation is required for mRNA nuclear export. In addition, I discovered a subset of SR proteins as a new class of mRNA export factors. These were originally thought to act solely as mRNA splicing factors, but I showed that they also interact with the mRNA export protein NXF1 to promote export. The work resulted in publications including 3 in Molecular Cell and 1 in PNAS, with an average citation of 356/paper. This work changed basic conceptions of mRNA export and my model has become the most widely accepted one for the role of SR proteins in mRNA export.

As an independent investigator, I first studied the function of the stem cell specific RNA binding protein LIN28, which is among four factors shown to reprogram somatic cells to induced pluripotent stem cells. The work led to 12 publications within a period of five years (2009-2013). I was invited to write a review article for WIRES RNA that was highlighted by the journal. The field once believed that blocking the biogenesis of the microRNA let-7 was the only function of LIN28, but my research showed that LIN28 is also a master posttranscriptional regulator of a subset of mRNAs involved in regulating cell growth and metabolism.

In the past 7 years, my research has extended to the evolutionarily conserved H19 long noncoding RNA (lncRNA). H19 has long been implicated in human genetic disorders and cancer. However, the physiological function and mode of action of H19 have remained elusive. We found that H19 inhibits let-7 function by acting as a molecular “sponge”. This work led to a seminal publication in Molecular Cell in 2013, cited 689 times. We also found that H19 interacts with and inhibits adenosylhomocysteine hydrolase (SAHH), the only mammalian enzyme capable of hydrolyzing S-adenosylhomocysteine, and a potent feedback inhibitor of SAM-dependent methyltransferases. The work published in Nature Communications in 2015 has been cited 87 times. Given that SAM-dependent methyltransferases direct methylation on a wide range of molecules including DNA, RNA, proteins, and lipids, and that let-7s comprise a major microRNA family known to play important roles in development, cancer and metabolism, our discovery of H19 in regulation of both SAHH and let-7 has the potential of impacting all of these areas. Indeed, we recently uncovered novel roles of H19 in glucose metabolism (Nucleic Acids Res, 2014; Cell Death Dis, 2017; JCI Insight, 2018; Diabetes, 2018), endometriosis (EMBO Mol Med, 2015), ovarian and endometrial cancers (Oncogene, 2015; Oncogene 2017), and uterine fibroids (Oncogene, 2019). My current research focus includes mechanistic dissection of H19 and TET proteins (a new class of DNA demethylases) in epigenetic regulation of gene expression, with the ultimate goal of discovering new molecular signatures and pathways for preventing and treating disorders such as diabetes and infertility.