Sive and her research group have made pioneering and unique contributions in many research areas and have developed multiple techniques.
Her research areas include analysis of the extreme anterior domain (EAD), a unique and important embryonic region she named.[4] 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.[5] 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 she co-devised, 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.[6] She also developed the first zebrafish 'explant' culture method, and so identified cell interactions that initiate brain development.[7] As well, Sive identified retinoic acid as a regulator of brain patterning, and demonstrated its activity on expression of hindbrain Hox genes.[8]
And she defined additional roles for fibroblast growth factors in precise patterning of the hindbrain.[9]
As structure and function are closely allied, Sive also focused on how the three-dimensional structure of the brain is generated by the processes of morphogenesis. Sive's group first identified and named "basal constriction" as a cell-shape-change occurring during brain morphogenesis.[10] In addition, they identified and named the process of "epithelial relaxation," a cell-sheet-stretching process that occurs as brain ventricles form.[11] Indeed, her group pioneered use of zebrafish to study the brain ventricular system—cavities filled with cerebrospinal fluid (CSF) that form the body's "third circulation."[12] Using a unique drainage assay, they identified Retinol Binding Protein in the CSF as essential for survival of brain cells.[13]
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.[14] 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.[15][16][17]
In running her eponymous lab, she is presently a professor in the UMass Boston Biology department. She was formerly a Member of the Whitehead Institute[18] and joined the MIT faculty in 1991.[19] The recipient of numerous awards at MIT, Sive was chosen as a Searle Scholar and received the National Science Foundation Young Investigator Award in 1992.
In November 2021, she was elected as an AAAS Fellow.[20] Sive received the recognition for fundamental discoveries advancing our understanding of early embryonic development, particularly the development of the nervous system in vertebrates, and for her leadership in teaching, mentoring, and diversity in higher education.[21]
In 2022, Sive was awarded an honorary doctorate in engineering from her alma mater, the University of the Witwatersrand.[22]
