Hazel Sive

Hazel L. Sive is a South African-born biologist and educator. She is a Member of Whitehead Institute for Biomedical Research, Professor of Biology at Massachusetts Institute of Technology and Associate Member of the Broad Institute of MIT and Harvard. Sive studies development of the vertebrate embryo, and has made unique contributions to understanding how the face forms and how the brain develops its normal structure. Her lab also seeks to understand the origins of neurological and neurodevelopmental disorders,[1] such as epilepsy, autism, Pitt–Hopkins syndrome and 16p11.2 deletion syndrome. In December 2019 it was announced that she will become the Dean of the College of Science at Northeastern University in June 2020.

Hazel Louise Sive
Hazel Sive in 2017
Alma mater
Awards
  • MacVicar Faculty Fellow, MIT (2015)
  • National Science Foundation Young Investigator Award (1992)
  • Searle Scholar Award (1992)
Scientific career
Institutions
Websitewi.mit.edu/people/faculty/sive

Education

Sive received her Bachelor of Science with honors in 1979 from the University of the Witwatersrand in Johannesburg, South Africa with a double major in zoology and chemistry.[2] She left South Africa for England where she taught secondary school science. She then went to the United States for graduate studies in molecular biology under Robert G. Roeder. She received a PhD from Rockefeller University in 1986.

Research

Sive is a pioneer in many research areas and has developed multiple techniques.

These include analysis of the extreme anterior domain (EAD), a unique and important embryonic region she named.[3] She used a simple anterior organ, the mucus-secreting cement gland of the frog Xenopus, to define the genetic network required for anterior position. The EAD also gives rise to the mouth and the Sive group has defined key steps necessary for mouth formation. Using their ‘facial transplant’ technique, her group made the unprecedented discovery that the EAD is also a facial signaling center, which guides neural crest cells into the developing face, where they form the jaws and other structures.[4] Since the EAD is present in humans, the work is directly relevant for understanding human craniofacial anomalies.

Another focus of Sive’s research has been nervous system patterning. Using novel techniques in subtractive cloning, her laboratory defined some of the earliest molecular markers and regulators of the nervous system in both Xenopus and the zebrafish Danio. Expression of these genes answered the age-old question of when the embryo decides to make a nervous system: Sive showed that future brain cells are set aside when the embryo is just a ball of cells. Function of these genes, including otx2 and zic1 (opl), was studied using hormone-inducible fusion proteins, a technique first used in embryos by Sive.[5] She also developed the first zebrafish ‘explant’ culture method, and so identified cell interactions that initiate brain development.[6] As well, Sive identified retinoic acid as a regulator of brain patterning, and demonstrated its activity on expression of hindbrain Hox genes.[7] And she defined additional roles for fibroblast growth factors in precise patterning of the hindbrain.[8]

As structure and function are closely allied, Sive also focuses on how three-dimensional structure of the brain is generated by the processes of morphogenesis. Sive first identified and named “basal constriction” as a cell-shape-change occurring during brain morphogenesis.[9] In addition, she identified and named the process of “epithelial relaxation,” a cell-sheet-stretching process that occurs as brain ventricles form.[10] Indeed, she pioneered use of zebrafish to study the brain ventricular system—cavities filled with cerebrospinal fluid (CSF) that form the body’s “third circulation.” [11] Using a unique drainage assay, Sive identified Retinol Binding Protein in the CSF as essential for survival of brain cells.[12]

Sive has a long-standing interest in neurodevelopmental disorders, including those relating to mental health. A great challenge is that these disorders often involve multiple genes, whose contributions to a disorder is frequently unclear. Sive pioneered zebrafish as a tool for probing gene function associated with autism spectrum disorders.[13] Her group has identified genes that interact and contribute to brain dysfunction in the prevalent and serious 16p11.2 deletion syndrome, most recently implicating lipid metabolism in symptomatology.[14][15]

Besides running her eponymous lab, she is also a faculty member at the Whitehead Institute.[16] She began teaching at MIT in 1991[2] and was chosen as a Searle Scholar the following year. She received the National Science Foundation Young Investigator Award in 1992, as well.

Academic roles

In 1993, Sive founded the Cold Spring Harbor Course on Early Development of Xenopus and taught this together with colleagues Richard Harland and Robert Grainger.[17] As of 2019, this course continues to run annually.

In 2015, she was named a MacVicar Faculty Fellow, MIT’s highest award for undergraduate teaching[18] She additionally received the MIT School of Science Teaching Award (2003) and MIT’s Alan J. Lazarus Advising Award in 2016.[19][20] She teaches on campus, and several of her courses are offered through the MIT OpenCourseWare online initiative.[21]

Sive was chair of the MIT Biology Undergraduate Program (2003-2006) and served as the first Associate Dean for the MIT School of Science (2006-2013), with oversight for education and equity.[22] During her tenure in that role, she was instrumental in compiling the 2011 Report on the Status of Women Faculty in the MIT Schools of Science and Engineering, which uncovered both positive aspects as well as an ongoing need for oversight of female faculty trajectory.[22] Sive has served aschair of MIT’s Committee on Student Life and as founding chair of MIT’s Faculty Postdoctoral Advisory Committee.[23]

In 2014, Sive founded and is Director of the MIT-Africa initiative, leading the Africa Advisory Committee to write a Strategic Plan for MIT Engagement in Africa.[24]

In 2017, Sive was named Director of Higher Education at the MIT Jameel World Education Lab (J-WEL).[23]

In December 2019 it was announced that Sive will become the Dean of the College of Science at Northeastern University in June 2020.[25]

References
  1. "Research | Sive Lab". sivelab.wi.mit.edu. Retrieved 2018-09-07.
  2. OpenCourseWare, MIT. "Hazel Sive | MIT OpenCourseWare | Free Online Course Materials". ocw.mit.edu. Retrieved 2017-11-26.
  3. Jacox, Laura A.; Dickinson, Amanda J.; Sive, Hazel (26 March 2014). "Facial Transplants in Xenopus laevis Embryos". Journal of Visualized Experiments (85). doi:10.3791/50697. PMC 4089428. PMID 24748020.
  4. Jacox, Laura; Chen, Justin; Rothman, Alyssa; Lathrop-Marshall, Hillary; Sive, Hazel (August 2016). "Formation of a "Pre-mouth Array" from the Extreme Anterior Domain Is Directed by Neural Crest and Wnt/PCP Signaling". Cell Reports. 16 (5): 1445–1455. doi:10.1016/j.celrep.2016.06.073. PMC 4972695. PMID 27425611.
  5. Kolm, Peggy J.; Sive, Hazel L. (September 1995). "Efficient Hormone-Inducible Protein Function in Xenopus laevis". Developmental Biology. 171 (1): 267–272. doi:10.1006/dbio.1995.1279. PMID 7556904.
  6. Sagerström, C. G.; Grinblat, Y.; Sive, H. (June 1996). "Anteroposterior patterning in the zebrafish, Danio rerio: an explant assay reveals inductive and suppressive cell interactions". Development. 122 (6): 1873–1883. ISSN 0950-1991. PMID 8674426.
  7. Kolm, Peggy J.; Sive, Hazel L. (January 1995). "Regulation of the Xenopus labial Homeodomain Genes, HoxA1 and HoxD1: Activation by Retinoids and Peptide Growth Factors". Developmental Biology. 167 (1): 34–49. doi:10.1006/dbio.1995.1005. PMID 7851655.
  8. Kolm, Peggy J.; Apekin, Vladimir; Sive, Hazel (December 1997). "XenopusHindbrain Patterning Requires Retinoid Signaling". Developmental Biology. 192 (1): 1–16. doi:10.1006/dbio.1997.8754. PMID 9405093.
  9. Gutzman, Jennifer H.; Graeden, Ellie G.; Lowery, Laura Anne; Holley, Heidi S.; Sive, Hazel (November 2008). "Formation of the zebrafish midbrain–hindbrain boundary constriction requires laminin-dependent basal constriction". Mechanisms of Development. 125 (11–12): 974–983. doi:10.1016/j.mod.2008.07.004. PMC 2780020. PMID 18682291.
  10. Gutzman, J. H.; Sive, H. (10 February 2010). "Epithelial relaxation mediated by the myosin phosphatase regulator Mypt1 is required for brain ventricle lumen expansion and hindbrain morphogenesis". Development. 137 (5): 795–804. doi:10.1242/dev.042705. PMC 2827689. PMID 20147380.
  11. Lowery, L. A. (23 March 2005). "Initial formation of zebrafish brain ventricles occurs independently of circulation and requires the nagie oko and snakehead/atp1a1a.1 gene products". Development. 132 (9): 2057–2067. doi:10.1242/dev.01791. PMID 15788456.
  12. Chang, Jessica T.; Lehtinen, Maria K.; Sive, Hazel (January 2016). "Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway". Developmental Neurobiology. 76 (1): 75–92. doi:10.1002/dneu.22300. PMC 4644717. PMID 25980532.
  13. Tropepe, V; Sive, HL (October 2003). "Can zebrafish be used as a model to study the neurodevelopmental causes of autism?". Genes, Brain, and Behavior. 2 (5): 268–81. doi:10.1034/j.1601-183X.2003.00038.x. PMID 14606692.
  14. Blaker-Lee, A.; Gupta, S.; McCammon, J. M.; De Rienzo, G.; Sive, H. (1 May 2012). "Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes". Disease Models & Mechanisms. 5 (6): 834–851. doi:10.1242/dmm.009944. PMC 3484866. PMID 22566537.
  15. McCammon, Jasmine M.; Blaker-Lee, Alicia; Chen, Xiao; Sive, Hazel (1 October 2017). "The 16p11.2 homologs fam57ba and doc2a generate certain brain and body phenotypes". Human Molecular Genetics. 26 (19): 3699–3712. doi:10.1093/hmg/ddx255. PMC 5886277. PMID 28934389.
  16. "Whitehead Institute - Faculty - Hazel L. Sive". wi.mit.edu. Retrieved 2017-11-26.
  17. "Roll of Honor". meetings.cshl.edu.
  18. "Current MacVicar Fellows | MIT Registrar". registrar.mit.edu.
  19. "Teaching prize recipients". MIT School of Science.
  20. "Office of Undergraduate Advising & Academic Programming | Awards Convocation". awards.mit.edu.
  21. "Hazel Sive | MIT OpenCourseWare | Free Online Course Materials". ocw.mit.edu.
  22. "Hazel Sive steps down as associate dean of the School of Science". MIT News.
  23. "Professor Hazel Sive". MIT J-WEL. 2 March 2018.
  24. "What is MIT-Africa?". MIT Africa.
  25. http://wi.mit.edu/news/archive/2019/sive-named-dean-northeastern-university
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