Member, Whitehead Institute
Professor of Biology, MIT
Whitehead Member Hazel Sive studies development of the vertebrate embryo. Her group has made unique contributions to understanding how the face forms and how the brain develops its normal structure. Research in the Sive lab emphasizes craniofacial and brain disorders, using the accessible frog and zebrafish models.
Sive is a pioneer in analysis of the extreme anterior domain (EAD), a unique and important embryonic region she named. She used a simple organ, the mucus-secreting cement gland of frogs, as a marker for the extreme anterior and to define the genetic network by which an organ is positioned. The EAD also gives rise to the mouth and the Sive group has defined key steps necessary for mouth formation. Unexpectedly, her group discovered 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. This work is relevant for understanding and treating human craniofacial defects.
A major focus of Sive’s research has been on development of the nervous system. Using novel techniques, her laboratory defined some of the earliest molecular markers of the nervous system. These answered the age-old question of when the embryo decides to make a nervous system, and showed that future brain cells are set aside when the embryo is just a ball of cells. A key area of interest is how three-dimensional structure of the brain is generated (the process of ‘morphogenesis’). The Sive group discovered a novel cell shape change they called ‘basal constriction’ and a cell sheet stretching process they called ‘epithelial relaxation’ that contribute to brain morphogenesis. Sive has used the zebrafish to study morphogenesis and function of the brain ventricular system - cavities filled with cerebrospinal fluid (CSF) that form the ‘third circulation’. Using a unique drainage assay, the Sive group has identified Retinol Binding Protein in the CSF as essential for survival of brain cells. Sive views this as just a start, and proposes that many proteins in the CSF play roles in brain health and disease.
Sive has a long-standing interest in understanding neurodevelopmental disorders, including those relating to mental health. A great challenge is that these disorders often involve multiple genes, which can be difficult to identify. Sive defined the zebrafish as a ‘tool’ for probing the functions of such genes, where although the fish is not human, it can nonetheless give insight into processes associated with disease. Using powerful assays allowed by the fish, the Sive group is identifying genes that interact and contribute to brain dysfunction.
Sive is a Member of the Whitehead Institute, Professor of Biology at MIT and Associate Member of the Broad Institute. Prof. Sive received the B.Sc. Hons. from the University of Witwatersrand in Johannesburg, South Africa, the Ph.D. in 1986 from Rockefeller University, New York; and carried out postdoctoral research at the Fred Hutchinson Cancer Center, Seattle, WA, before joining the MIT faculty in 1991. Sive was the first Associate Dean for the MIT School of Science and is Founding Coordinator of the MIT-AFRICA Initiative. Most recently, she was named a 2015 MacVicar Faculty Fellow, MIT’s highest teaching award.
- Defined the Extreme Anterior Domain as a crucial region in face formation
- Identified novel genes and processes required for normal brain development, which contribute to neurodevelopmental and mental health disorders
- Searle Scholar 1992
- National Science Foundation Young Investigator Award 1992
- Latham Family Career Development Professor 1994-1997
- Associate Dean, MIT School of Science 2006-2013
- Founding Director MIT-South Africa Program 2013
- Founding Coordinator MIT-AFRICA Initiative 2014
- MacVicar Faculty Fellow 2015