PhD, University of Virginia
BS, University of Kentucky
Postdoctoral Research, The Wistar Institute, Philadelphia, PA
My research is devoted to understanding the molecular mechanisms that regulate early mammalian embryogenesis, and how disruptions in early developmental events can lead to disease later in life. In seeking to understand the early embryo, my research also incorporates the biology of gametes and gametogenesis, particularly the oocyte and oogenesis. This leads into studies of interactions between the oocyte and follicle cells. Additionally, the mechanisms that establish early cell lineages are examined. For over 20 years my laboratory has developed and applied methods for detailed molecular studies of oocytes, embryos, and stem cells. My research encompasses genetics, epigenetics, cell biology, cell physiology, and gene network analysis, providing for a comprehensive approach. This includes heavy use of genome, epigenome, bioinformatic and transcriptome analysis technologies. These genetic, genomic and molecular studies are coupled to microsurgical methods, such as nuclear transfer, cloning, cytoplasm transfer, microinjection, and sperm injection. This powerful combination of methods enables in-depth study of the controlling mechanisms operating inside mammalian oocytes and embryos, despite their limited availability, cost, and small size. Through an NIH-funded (R24) Primate Embryo Gene Expression Resource (PREGER), my lab contributed a large amount of novel data to the field of primate embryology. Our discoveries highlight the importance of nonhuman primates as research models, as we have documented many profound differences as compared to rodent models. Other studies take advantage of mouse genetic models to identify novel molecular pathways controlling oogenesis and embryogenesis, and to study environmental effects on these processes. Most recently, we have engaged in applying gene editing technologies in embryos. Future plans include the incorporation of other model organisms and the broader study of the effects of environmental toxins on reproduction.
Developmental Origins of Disease
Ruebel ML, Schall PZ, Midic U, Vincent KA, Goheen B, VandeVoort, CA, Latham KE. Transcriptome analysis of rhesus monkey failed-to-mature oocytes: deficiencies in transcriptional regulation and cytoplasmic maturation of the oocyte mRNA population. Mol. Hum. Reprod. 2018 (in press).
Midic, U, VandeVoort, CA, Latham, KE. Determination of single embryo sex in Macaca mulatta an Mus musculusRNAseq transcriptome profiles. Pysiol Genomics. 2018; (in press).
Midic U, Goheen B, Vincent KA, VandeVoort CA, Latham KE. Changes in gene expression following long-term in vitro exposure of Macaca mulatta trophoblast stem cells to biologically relevant levels of endocrine disruptors. Reprod Toxicol. 2018; 77: 154-165.
Ding D, Liu J, Midic U, Wu Y, Dong K, Melnick A, Latham KE, Chen C. TDRD5 binds piRNA precursors and selectively enhances pachytene piRNA processing in mice. Nat. Comm. 2018; Jan 9: 127-139.
Midic U, Vincent KA, Wang K, Lokken A, Severance, AL, Ralston A, Knott J, Latham KE. Novel key roles for of Structural maintenance of chromosome flexible domain containing 1 (Smchd1) during preimplantation mouse development. Mol Reprod. Dev. 2018; (in press).
Severance AL, Latham KE. PLK1 regulates spindle association of phosphorylated eukaryotic translation initiation factor 4E binding protein, and spindle function in mouse oocytes. Amer. J. Physiol, Cell Physiol. 2017; 313:C501-515.
Midic U, Hung C, Vincent KA, Goheen B, Schupp PG, Bauer DA, VandeVoort CA, Latham KE. Quantitative assessment of timing, efficiency, specificity, and genetic mosaicism of CRISPR/Cas9 mediated gene editing of hemoglobin beta gene in rhesus monkey embryos. Hum Mol. Genet. 2017; 26:2678-89.
Midic U, Vincent KA, VandeVoort CA, Latham KE. Effects of endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells. Repro. Toxicol 2016; 65: 382-93.