Maria Mikedis Nicholson

Maria M. Mikedis, PhD


  • Assistant Professor, UC Department of Pediatrics

About

Biography

I am a researcher focused on stem cell biology, spermatogenesis, reproduction and developmental biology. I became interested in development and reproduction when I worked as an undergraduate researcher in Blanche Capel's lab at Duke University, studying testis development in the embryo. These interests have stayed with me throughout my career.

During my graduate work with Karen Downs at the University of Wisconsin–Madison, we used classical and modern fate-mapping techniques to study embryogenesis and the formation of the cellular population that ultimately becomes sperm or egg. For my postdoctoral fellowship, I applied functional genomic approaches to developmental questions and worked with David Page at the Whitehead Institute to examine the roles of key proteins that post-transcriptionally regulate ribonucleic acid (RNA) during spermatogenesis.

My lab's research centers on how spermatogonial stem cells in the testis differentiate to form sperm. Spermatogonial stem cells produce progenitors that divide mitotically to rapidly expand their population in the testis. Advanced progenitors then stop dividing mitotically and initiate meiosis, the specialized cell division that halves the genome to produce gametes. Afterward, the cells complete meiosis and undergo additional cellular differentiation to form sperm. We are particularly interested in how the post-transcriptional control of messenger ribonucleic acid (mRNA) facilitates two distinct stages of development: 1. spermatogonial stem cell differentiation into mitotically dividing progenitors, and 2. progenitors' initiation of meiosis. One of my major discoveries is that spermatogonial stem cells require DAZL, an RNA-binding protein, to produce a large progenitor pool. DAZL facilitates progenitor expansion by increasing the translation of its mRNA targets.

One challenge to studying sperm development is that the testis is a complex tissue with all stages of sperm development present at the same time. We use two complementary approaches to overcome this developmental complexity: single-cell sequencing and a specialized approach that developmentally synchronizes spermatogenesis. By combining these approaches with genetics, biochemistry, functional genomics and bioinformatics, we can make powerful insights into the development of sperm.

I am honored to have received several awards, including:

  • National Institutes of Health (NIH) Pathway to Independence Award (K99/R00) from the National Institute of Child Health and Human Development (NICHD) (2020 – 2025)
  • Sokol Postdoctoral Award in Biomedical Research from the Whitehead Institute (2021)
  • Leading Edge Fellow (2021)
  • NIH National Research Service Award (NRSA) Postdoctoral Fellowship (F32) from NICHD (2017 – 2020)
  • Lalor Foundation Postdoctoral Fellowship (2016 – 2017)
  • 61st Annual Lindau Meeting of Nobel Laureates and Students selected attendee (2011)
  • National Science Foundation Research Fellowship (2011 – 2014)

I have been a researcher for over 15 years and began my work at Cincinnati Children’s in 2022.

Publications

DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors. Mikedis, MM; Fan, Y; Nicholls, PK; Endo, T; Jackson, EK; Cobb, SA; de Rooij, DG; Page, DC. eLife. 2020; 9.

Dynamic and regulated TAF gene expression during mouse embryonic germ cell development. Gura, MA; Mikedis, MM; Seymour, KA; de Rooij, DG; Page, DC; Freiman, RN. PLoS Genetics. 2020; 16.

Retinoic Acid and Germ Cell Development in the Ovary and Testis. Endo, T; Mikedis, MM; Nicholls, PK; Page, DC; de Rooij, DG. Biomolecules. 2019; 9.