About the Program
- Use of molecular evolutionary and comparative genomic approaches to understand genetic change during human evolution
- The study of the evolution of parturition in mammals
- Use of comparative genomic data to test evolutionary hypotheses in genes implicated in preterm birth in humans
- Course in evolution of reproduction
- Monthly Journal Club for the discussion of major breakthroughs in the field
- To conduct original research on the evolution of human placentation and its relationship to disease
- To use the tools of molecular evolutionary biology to understand the biology of normal pregnancy and adverse pregnancy outcome
- Training of graduate students, post-doctoral fellows and clinical Maternal-Fetal Medicine fellows
- The evolutionary history of birth and labor
- The evolutionary history of the human placenta
- Evolution of genes that play an important role in human pregnancy
- Changes in gene expression in placental, non-placental mammals, and other species
- Application of computational biology and bioinformatics to understand the evolution of the maternal-fetal relationship
Important Points & Discoveries
- The hemochorial placenta evolved early during mammalian evolution. This finding challenges the prevailing view that the hemochorial placentation is a ‘derived’, rather than an ancient form
- Galectins are key molecules that might participate in tolerance, especially during primate pregnancies
- The gene encoding the progesterone receptor has undergone adaptive changes during recent human evolution
- Unraveling of the relationships among placental mammals using phylogenomic methods
- Natural selection pressures are different in genes highly expressed in the prenatal when compared to those in the postnatal environments
- Hou ZC, Sterner KN, Romero R, Than NG, Gonzalez JM, Weckle A, Xing J, Benirschke K, Goodman M, Wildman DE. Elephant transcriptome provides insights into the evolution of eutherian placentation. Genome Biol Evol 2012;4:713-25.
- Than NG, Romero R, Kim CJ, McGowen MR, Papp Z, Wildman DE. Galectins: guardians of eutherian pregnancy at the maternal-fetal interface. Trends Endocrinol Metab 2012 Jan;23:23-31.
- Wildman DE, Chen C, Erez O, Grossman LI, Goodman M, Romero R. Evolution of the mammalian placenta revealed by phylogenetic analysis. Proc Natl Acad Sci U S A 2006 Feb;103:3203-8.
- Wildman DE, Uddin M, Opazo JC, Liu G, Lefort V, Guindon S, Gascuel O, Grossman LI, Romero R, Goodman M. Genomics, biogeography, and the diversification of placental mammals. Proc Natl Acad Sci U S A 2007 Sep;104:14395-400.
- Chen C, Opazo JC, Erez O, Uddin M, Santolaya-Forgas J, Goodman M, Grossman LI, Romero R, Wildman DE. The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor. Mol Phylogenet Evol 2008 May;47:637-49.
- Uddin M, Goodman M, Erez O, Romero R, Liu G, Islam M, Opazo JC, Sherwood CC, Grossman LI, Wildman DE. Distinct genomic signatures of adaptation in pre- and postnatal environments during human evolution. Proc Natl Acad Sci U S A 2008 Mar;105:3215-20.
- Hou Z, Romero R, Uddin M, Than NG, Wildman DE. Adaptive history of single copy genes highly expressed in the term human placenta. Genomics 2009 Jan;93:33-41
ABOUT THE PROGRAM
- The regulation of mitochondrial function during normal placental development
- Delineation of the effects of inflammation on mitochondrial function in a cell and tissue culture model and characterization of a pathway for the observed effects
- To understand how MNRR1 mediated mitochondrial function relates to organellar activity throughout pregnancy, and therefore the repercussions of an inflammatory insult on MNRR1-mediated mitochondrial dysfunction
- How do inflammatory stimuli induce mitochondrial dysfunction?
- What is the pathway by which LPS affects mitochondrial function?
- How does stress regulator MNRR1 (CHCHD2) function during plaental inflammation?
IMPORTANT POINTS & DISCOVERIES
- In preliminary data, MNRR1 decreases duering placental inflammation, inhibiting mitochondrial function.
- Aras S, Arrabi H, Purandare N, Hüttemann M, Kamholz J, Züchner S, Grossman LI. (2017). Abl2 kinase phosphorylates bi-organellar regulator MNRR1 in mitochondria, stimulating respiration. Biochim Biophys Acta 1864, 440-448.
- Sommer N, Hüttemann M, Pak O, Scheibe S, Knoepp F, Sinkler C, Malczyk M, Gierhardt M, Esfandiary A, Kraut S, Jonas F, Veith C, Aras S, Sydykov A, Alebrahimdehkordi N, Giehl K, Hecker M, Brandes RP, Seeger W, Grimminger F, Ghofrani HA, Schermuly RT, Grossman LI, Weissmann N (2017). Mitochondrial complex IV subunit 4 isoform 2 is essential for acute pulmonary oxygen sensing. Circ Res 121, 424-438.
- Purandare N, Somayajulu M, Hüttemann M, Grossman LI, Aras S. (2018). The cellular stress proteins CHCHD10 and MNRR1 (CHCHD2): Partners in mitochondrial and nuclear function and dysfunction. J Biol Chem 293, 6517-6529