Section: Rotations

Postdoctoral Position Available

Daniel Kilpatrick, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Physiology

Other Affiliation(s):
   Cell Biology
   Program in Neuroscience

Rotation Projects

Transcriptional Determinants of Neurogenesis

During neurogenesis, neural progenitor cells in different regions of the nervous system give rise to neurons (and glia) in a process known as terminal differentiation. While all neurons share several common features, each population possesses a unique phenotype related to their specific functions (e.g., dendritic fields, axonal projections and synaptic connections, neurotransmitters and receptors, etc). Further, the onset of this process is initiated once neuronal progenitors exit the cell cycle. That is, progenitor growth arrest activates a series of transcriptional pathways that give rise to not only general neuronal features, but also to neuronal subtype-specific gene expression. We are interested in understanding the transcriptional control of this process at several levels in the context of cerebellar granule neurons (CGNs). We are currently addressing the following questions:

1. How is the decision by neuronal progenitors to stop dividing linked to onset of the terminal differentiation program? In this case, we are identifying those transcription factors that operate at the interface between the growth arrest and differentiation programs in CGNs, whit a specific focus on the E2F family. These proteins play a pivotal role during cell cycle events, and we have recently demonstrated their importance in neuronal differentiation as well. We are now performing functional studies of E2F proteins using viral expression vectors as well as knockout mice to determine their precise roles.



2. Which transcription factors participate in the regulatory cascades leading to the final stage of terminal differentiation, as well as neuronal subtype specificity? Here we are focusing on the late phase of terminal neuronal differentiation, dendritogenesis-synaptogenesis, in CGNs. Little is currently known of how these final, critical events of neurodevelopment are elaborated. To this end, we are identifying and functionally characterizing the key transcriptional players controlling these processes using: a) microarrays to identify candidate transcription factors that are developmentally expressed during late terminal differentiation; b) transgenic promoter analysis and expression cloning of DNA binding proteins to define the factors regulating the GABAA 6 receptor subunit gene, which is highly upregulated during dendrite formation of CGNs. This gene is also expressed exclusively by CGNs, and thus provides insight into transcriptional mechanisms controlling neuronal subtype-specification. Viral expression vectors and in vivo studies will be used to define the specific roles of transcriptional regulators identified using the above approaches.

Office: S4-139
Phone: 508-856-6274
E-mail: Daniel.Kilpatrick@umassmed.edu
Keywords: Neurobiology, Gene Regulation, Testis Development, Developmental Biology, Transgenic Mice

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Postdoctoral Position Available An NIH-funded postdoctoral position in Molecular Neuroscience is available immediately to study transcriptional programming and chromatin regulation of neurodevelopment and associated disorders. Our lab uses multiple approaches including gene knockouts, BAC transgenics, shrnas, viral expression, microarrays, chromatin IP, ChIP-Seq and related molecular techniques.  Ph.D. with experience in molecular biology is important, and expertise in protein-DNA interactions and/or molecular neuroscience preferred.  Send CV and names of three references to: Dr. Dan Kilpatrick, Department of Physiology and Neuroscience Program, UMASS Medical School, Worcester, MA  e-mail: daniel.kilpatrick@umassmed.edu. The University of Massachusetts Medical School is an Affirmative Action / Equal Opportunity Employer.