Keith Latham, PhD
Education/Degree Information
- PhD, University of Virginia
- BS, University of Kentucky
- Postdoctoral Research, The Wistar Institute, Philadelphia, PA
Title
- Co-Director Reproductive and Developmental Sciences NIH T32 Training Program
- Co-Director Doctoral Student Recruitment and Retention Program (DSRRP)
- Professor of Animal Science and Adjunct Professor, Department of Obstetrics, Gynecology and Reproductive Biology.
RESEARCH INTEREST
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 nearly 30 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 combined with 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. My research has involved mouse and nonhuman primate research models and most recently expanded to the bovine model. Current interests include understanding evolutionary divergence between mammals affecting oocyte and embryo biology. Many studies take advantage of mouse genetic models to identify novel molecular pathways controlling oogenesis and embryogenesis, and to study environmental effects on these processes. Current research interests focus on understanding the regulation of maternal mRNA in oocytes and early embryos, the regulation of embryonic transcriptional genome activation, and the role of endocrine factors in regulating oocyte and embryo quality.
RESEARCH TOPICS
- Preimplantation Embryology
- Oocyte Biology
- Meiosis
- Gene Editing
- Developmental Origins of Disease
RECENT PUBLICATIONS
Schall PZ, Latham KE.Predictive modeling of oocyte maternal mRNA features of five mammalian species reveals potential shared and species-restricted regulators during maturation.
Physiol Genomics. 2023 Oct 16. doi: 10.1152/physiolgenomics.00048.2023. PMID: 37842744
Karl KR, Schall PZ, Clark ZL, Ruebel ML, Cibelli J, Tempelman RJ, Latham KE, Ireland JJ.Ovarian stimulation with excessive FSH doses causes cumulus cell and oocyte dysfunction in small ovarian reserve heifers. Mol Hum Reprod. 2023 Sep 30;29(10):gaad033. doi: 10.1093/molehr/gaad033. PMID: 37713463
Latham KE.Preimplantation embryo gene expression: 56 years of discovery, and counting.Mol Reprod Dev. 2023 90:169-200. doi: 10.1002/mrd.23676. Epub 2023 Feb 22. PMID: 36812478.
Ruebel ML, Martins LR, Schall PZ, Pursley JR, Latham KE. Effects of early lactation body condition loss in dairy cows on serum lipid profiles and on oocyte and cumulus cell transcriptomes. J Dairy Sci. 2022 105:8470-8484. doi: 10.3168/jds.2022-21919. PMID: 35940920
Clark ZL, Ruebel ML, Schall PZ, Karl KR, Ireland JJ, Latham KE. Follicular Hyperstimulation Dysgenesis: New Explanation for Adverse Effects of Excessive FSH in Ovarian Stimulation.Endocrinology. 2022 163:bqac100. doi: 10.1210/endocr/bqac100.PMID: 35833461.
Karl KR, Ireland JLH, Clark ZL, Tempelman RJ, Latham KE, Ireland JJ. Limitations in use of ovarian reserve biomarkers to predict the superovulation response in small ovarian reserve heifers. Theriogenology. 2022 182:53-62. doi: 10.1016/j.theriogenology.2022.01.033. PMID: 35123311.
Clark ZL, Karl KR, Ruebel ML, Latham KE, Ireland JJ . Excessive follicle-stimulating hormone during ovarian stimulation of cattle may induce premature luteinization of most ovulatory-size follicles. Biol Reprod. 2022 106:968-978. doi: 10.1093/biolre/ioac021.PMID: 35084014.
Schall PZ, Latham KE. Cross-species meta-analysis of transcriptome changes during the morula-to-blastocyst transition: metabolic and physiological changes take center stage. Am J Physiol Cell Physiol. 2021 321:C913-C931. doi: 10.1152/ajpcell.00318.2021. PMID: 34669511.
Schall PZ, Latham KE. Essential shared and species-specific features of mammalian oocyte maturation-associated transcriptome changes impacting oocyte physiology. Am J Physiol Cell Physiol. 2021 321:C3-C16. doi: 10.1152/ajpcell.00105.2021. PMID: 33881934.
Ruebel ML, Zambelli F, Schall PZ, Barragan M, VandeVoort CA, Vassena R, Latham KE. Shared aspects of mRNA expression associated with oocyte maturation failure in humans and rhesus monkeys indicating compromised oocyte quality. Physiol Genomics. 2021 53(4):137-149. doi: 10.1152/physiolgenomics.00155.2020. PMID: 33554756.
Karl KR, Jimenez-Krassel F, Gibbings E, Ireland JLH, Clark ZL, Tempelman RJ, Latham KE, Ireland JJ. Negative impact of high doses of follicle-stimulating hormone during superovulation on the ovulatory follicle function in small ovarian reserve dairy heifers†.
Biol Reprod. 2021 104:695-705. doi: 10.1093/biolre/ioaa210. PMID: 33205153.
Eroglu B, Szurek EA, Schall P, Latham KE, Eroglu A. Probing lasting cryoinjuries to oocyte-embryo transcriptome. PLoS One. 2020 Apr 6;15(4):e0231108. doi: 10.1371/journal.pone.0231108. PMID: 32251418.
Ruebel ML, Latham KE. Listening to mother: Long-term maternal effects in mammalian development.Mol Reprod Dev. 2020 87:399-408. doi: 10.1002/mrd.23336. PMID: 32202026 Review.
Severance AL, Midic U, Latham KE.Genotypic divergence in mouse oocyte transcriptomes: possible pathways to hybrid vigor impacting fertility and embryogenesis. Physiol Genomics. 2020 52:96-109. doi: 10.1152/physiolgenomics.00078.2019. PMID: 31869285
Schall PZ, Ruebel ML, Latham KE. A New Role for SMCHD1 in Life's Master Switch and Beyond. Trends Genet. 2019 35:948-955. doi: 10.1016/j.tig.2019.10.001. PMID: 31668908 Review.
Ruebel ML, Vincent KA, Schall PZ, Wang K, Latham KE. SMCHD1 terminates the first embryonic genome activation event in mouse two-cell embryos and contributes to a transcriptionally repressive state. Am J Physiol Cell Physiol. 2019 317:C655-C664. doi: 10.1152/ajpcell.00116.2019. PMID: 31365290
Mossa F, Latham KE, Ireland JJ, Veiga-Lopez A. Undernutrition and hyperandrogenism during pregnancy: Role in programming of cardiovascular disease and infertility. Mol Reprod Dev. 2019 86:1255-1264. doi: 10.1002/mrd.23239. PMID: 31347224 Review.
Brachova P, Alvarez NS, Hong X, Gunewardena S, Vincent KA, Latham KE, Christenson LK. Inosine RNA modifications are enriched at the codon wobble position in mouse oocytes and eggs. Biol Reprod. 2019 101:938-949. doi: 10.1093/biolre/ioz130. PMID: 31346607
Schall PZ, Ruebel ML, Midic U, VandeVoort CA, Latham KE. Temporal patterns of gene regulation and upstream regulators contributing to major developmental transitions during Rhesus macaque preimplantation development. Mol Hum Reprod. 2019 25:111-123. doi: 10.1093/molehr/gaz001. PMID: 30698740
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 24:478-494. doi: 10.1093/molehr/gay032. PMID: 30085220
Midic U, Vincent KA, Wang K, Lokken A, Severance AL, Ralston A, Knott JG, Latham KE. Novel key roles for structural maintenance of chromosome flexible domain containing 1 (Smchd1) during preimplantation mouse development. Mol Reprod Dev. 2018 85:635-648. doi: 10.1002/mrd.23001. PMID: 29900695
Midic U, VandeVoort CA, Latham KE. Determination of single embryo sex in Macaca mulatta and Mus musculus RNA-Seq transcriptome profiles. Physiol Genomics. 2018 50:628-635. doi:10.1152/physiolgenomics.00001.2018. PMID: 29727590
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. doi: 10.1016/j.reprotox.2018.02.012. PMID: 29505797