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Heidi Cook-Anderson

Research

Did you know that the earliest stages of life -- from worms to humans -- occurs in the absence of transcription? I found this single fact so remarkable that it determined the entire direction of my career. Below are examples of the types of questions we are working to answer in the laboratory. To address these questions, we are integrating cutting-edge approaches in RNA, epigenetics, chromatin, and computational biology. And we are investigating these questions in mammals, using oocyte, embryo and stem-cell based models for the mouse and human.

Gene regulatory mechanisms driving development from oocyte to embryo

The transition from a fully differentiated oocyte to a totipotent embryo is arguably one of the most dynamic transitions in all of biology. As mentioned above, this transition from oocyte to embryo occurs in the absence of new transcription. Transcription is globally silenced in the oocyte before ovulation, and reactivation of transcription from the new embryonic genome does not fully resume until the late 2-cell embryo stage in mice and even later at the 4 to 8-cell stage in humans. Many developmental events essential for the earliest stages of life occur during this period of transcriptional silence, including oocyte maturation, fertilization, wide-spread epigenetic and chromatin structural changes, the first mitotic cell division(s), and finally, reactivation of transcription in the newly formed embryo. Without transcription, control of gene expression to drive these critical steps relies on post-transcriptional processes unique to the oocyte and embryo. How this complex gene regulation is orchestrated and how each of these developmental transitions are accomplished in the absence of transcription are major questions we are working to address.

Reprogramming the fully differentiated oocyte to the totipotent embryo

Stem cell reprogramming holds enormous potential for the study and treatment of disease. However, while many exciting advances have been made, cell reprogramming in vitro remains inefficient, and this inefficiency is a major limitation in the field. In contrast, reprogramming of a fertilized egg to a totipotent (not just pluripotent) embryo is highly efficient. And this efficiency is essential for life from worms to humans. Therefore, another important goal in the lab is to dissect the mechanisms required for efficient nuclear and cytoplasmic reprogramming across the transition from oocyte to embryo and to apply the insights learned to improve stem cell reprogramming in vitro.

Uncovering the molecular determinants of successful implantation of the human blastocyst

We, as humans, are remarkably inefficient at reproducing ourselves compared to other animals. The reasons for this remain poorly understood; however, high rates of molecular or genetic defects in human embryos leading high rates of implantation failure are thought to be a major contributor. In fact, early implantation failure is estimated to account for ~70% of lost pregnancies and is widely considered to be one of the greatest obstacles in treating infertility. Advances in the field have been limited for decades as the factors and pathways important for implantation in humans largely remain a black box. We are working to identify these factors and pathways critical for successful implantation of the human blastocyst and to develop stem-cell based models to dissect the underlying molecular mechanisms required. We hope these studies will provide much needed insight into the earliest stages of our own development and to improve implantation success in the IVF clinic.

Select Publications

  • Chousal JN, Sohni A, Vitting-Seerup K, Cho K, Kim M, Tan K, Porse B, *Wilkinson MF, and *Cook-Andersen H. Progression of the pluripotent epiblast depends upon the NMD Factor UPF2. (2022). Development 149(21):dev200764. *Co-communicating authors.
  • Tan K*, Jones SH*, Lake BB, Dumdie JN, Shum EY, Zhang L, Chen S, Sohni A, Pandya S, Gallo RL, Zhang K, Cook-Andersen H and Wilkinson MF. The role of the NMD factor UPF3B in olfactory sensory neurons. (2020). eLife 9:e57525. *Contributed equally
  • Ramaiah M*, Tan K*, Plank T-D, Song H-W, Dumdie JN, Jones S, Shum EY, Sheridan SD, Peterson KJ, Gromoll J, Haggarty SJ, Cook-Andersen H and Wilkinson MF. FX-MIR: a microRNA cluster in the Fragile X region that targets FMR1. (2019). EMBO Rep 20(2): 46566. *Contributed equally
  • Wilkinson MF and Cook-Andersen H. Nonsense shielding: protecting RNA from decay leads to cancer. (2019). EMBO J 38(3): e101417.
  • Dumdie J*, Cho K*, Ramaiah M*, Skarbrevik D, Castilla S, Stumpo D, Lykke-Andersen J, Laurent L, Blackshear P, Wilkinson MF and Cook-Andersen H. Global transcriptional silencing and developmental competence in the oocyte mediated by the mRNA decay activator Zfp36l2. (2018). Developmental Cell 44(3): 392. *Contributed equally to this work.
  • Huang L, Shum EY, Jones SH, Lou C-H, Dumdie J, Kim H, Roberts AJ, Jolly LA, Skarbrevik DM, Phan MH, Swerdlow NF, Gecz J, Cook-Andersen H and Wilkinson MF. (2017). A Upf3b-mutant mouse model with behavioral and neurogenesis defects. (2017). Molecular Psychiatry 23(8): 1773.
  • Burt-Solorzano CM, Helm KD, Patrie JT, Shayya RF, Cook-Andersen HL, Chang RJ, McCartney CR, and Marshall JC. (2017). Increased Adrenal Androgen Production in Overweight Peri-Pubertal Girls. Journal of the Endocrine Society 1(5): 538.
  • Shum EY, Jones SH, Shao A, Dumdie J, Krause MD, Chan WK, Lou CH, Espinoza JL, Song H, Phan, MH, Ramaiah, M, Huang, L, McCarrey, JR, Peterson KJ, De Rooij, Cook-Andersen H and Wilkinson MF. (2016). Antagonistic Gene Paralogs Govern Nonsense-Mediated RNA Decay. Cell 165(2):382-95.
  • Cook-Andersen H‡, Curnow K, Chang RJ and Shimasaki S‡. Recombinant growth and differentiation factor-9 stimulates growth of both the oocyte and granulosa cell compartments of the primary follicle during in vitro culture. (2016). Journal of Assisted Reproduction and Genetics 33(8):1067. ‡Co-communicating authors.
  • Mora-Castilla S, To C, Vaezeslami S, Morey R, Srinivasan S, Dumdie JN, Cook-Andersen H, Jenkins J, and Laurent L. (2016). Miniaturization Technologies for Efficient Single-cell Library Preparations and Next-Generation Sequencing. Journal of Laboratory Automation 21(4):557.
  • Lou CH, Dumdie J, Shum E, Brafman D, Goetz A, Liao XY, Castilla S, Ramaiah M, Cook-Andersen H, Laurent L and Wilkinson MF. NMD Dictates Human Embryonic Stem Cell Fate. (2016). Stem Cell Reports 6(6): 844.
  • Hou J, Cook-Andersen H, Maas KH, Burt-Solorzano C, Shayya R, Kumar A and Chang RJ. HCG-Stimulated 17-OHP Responses and Basal Serum AMH Levels Among Adolescent Women with Polycystic Ovary Syndrome. (2016). Journal of Pediatric Metabolism and Endocrinology 29(7):835.
  • Maas KH, Chuan SS, Cook-Andersen H, Hou J, Su HI, Duleba A, and Chang RJ. Androgen Responses to ACTH Infusion among Individual Women with Polycystic Ovary Syndrome. (2016). Fertility and Sterility 106(5): 1252.
  • Cook-Andersen H and Wilkinson MF. (2015). Splicing does the two-step. Nature 521(7552):300-301. PMID:25970243.
  • Cook-Andersen H, Chuan SS, Maas K, Rosencrantz M, Su HI, Lawson M, Mason H and Chang RJ. Lack of Serum Anti-Mullerian Hormone Responses Following Recombinant Human Chorionic Gonadotropin Stimulation in Women with Polycystic Ovary Syndrome. (2014). Journal of Clinical Endocrinology and Metabolism 100(1):251-257.
  • Maas KH, Chuan SS, Cook-Andersen H, Su HI, Duleba A, and Chang RJ. Relationship between 17-hydroxyprogesterone Responses to Human Chorionic Gonadotropin and Markers of Ovarian Follicle Morphology in Women with Polycystic Ovary Syndrome. (2014). Journal of Clinical Endocrinology and Metabolism 100 (1):293-300.
  • Shayya RF, Rosencrantz MA, Chuan SS, Cook-Andersen H, Haggan A, Su HI, Roudebush WE, Shimasaki S, and Chang RJ. (2014). Decreased Inhibin B Responses Following Recombinant hCG Administration in Normal Women and Women with Polycystic Ovary Syndrome. Fertility and Sterility 101(1):275-279.
  • Chang RJ, Cook-Andersen H. (2013). Disordered Follicle Development in PCOS. Molecular and Cellular Endocrinology 373(1-2):51-60.
  • Cook HL, Lytle JR, Mischo HE, Li M-J, Rossi JJ, Silva DP, Desrosiers RC, and Steitz JA. (2005). Small Nuclear RNAs Encoded by Herpesvirus saimiri Upregulate the Expression of Genes Linked to T Cell Activation in Virally Transformed T Cells. Current Biology 15(10):974-979.
  • Cook HL, Mischo HE, and Steitz JA. (2004). The Herpesvirus saimiri Small Nuclear RNAs Recruit AU-Rich Element-Binding Proteins but Do Not Alter Host AU-Rich Element-Containing mRNA Levels in Virally Transformed T Cells. Molecular and Cellular Biology 24:4522-4533.

Biography

Heidi Cook-Andersen completed her M.D./Ph.D. at Yale University as a Howard Hughes Predoctoral Fellow in the laboratory of Dr. Joan A. Steitz. Dr. She completed her residency training in Obstetrics and Gynecology at the University of Colorado Health Sciences Center and subspecialty fellowship training in Reproductive Endocrinology and Infertility at UC San Diego. She has been a recipient of both the NIH Women’s Reproductive Health Research Award and the Burroughs Wellcome Fund CAMS Award. She joined the faculty in 2017 and holds a joint appointment with the Department of Molecular Biology and Department of Reproductive Sciences.

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