Section: Research

Postdoctoral Position Available

Charles Sagerstrom, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Interdisciplinary Graduate Program

Gene expression in embryogenesis

Formation of the vertebrate central nervous system (CNS) begins early during embryogenesis - at gastrula stages, but extensive refinements continue to take place before the fully functional adult CNS emerges. Neural development is carefully controlled and perturbations of this process give rise to defects ranging from severe developmental abnormalities to mild cognitive impairments. We are studying genes that control early neural development, particularly formation of the caudal CNS (hindbrain and spinal cord) in the zebrafish, using a three-step strategy. 

Gene discovery
We are screening for novel genes involved in neural development by several approaches.  First, we have used subtractive hybridization to isolate genes expressed specifically in the caudal CNS. Second, we are using ‘expression profiling’ to identify novel genes expressed downstream of paralog group 1 hox genes in the caudal hindbrain.  Third, we are undertaking a haploid genetic screen for mutations affecting hindbrain development.  Fourth, we are using co-precipitation together with MALDI-TOF analysis to identify interacting partners of proteins known to regulate hindbrain development.

Derive genetic pathways
We next integrate these genes into pathways that drive hindbrain development, using a number of molecular genetic approaches. For instance, we use injection of synthetic mRNA to ectopically activate gene function in wild type embryos, or to rescue defects in various mutant lines, and we use antisense technology to ‘knock-down’ the function of specific genes. We have recently begun generating transgenic lines that will provide better spatiotemporal control for these types of misexpression studies.

Define biochemical activities
Lastly, we define the function of the various gene products using a variety of biochemical approaches.  For instance, we carry out reporter assays in transfected cell lines, analyze protein:protein interactions in vivo and in vitro and study histone acetylation using embryo lysates.

Office: LRB-815, Lab 870 D-F
Phone: 508-856-8006
E-mail: Charles.Sagerstrom@umassmed.edu
Keywords: Neurobiology, Gene Expression, Developmental Biology

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Sagerström for additional details.