Keller Lab

The Keller lab is interested in the molecular and genetic mechanisms of organ and tissue identity. In multicellular organisms, each cell in the body has the exact same copy of the genome, and yet it is readily apparent that the organs of the body are structurally diverse and functionally specialized. What is the genetic basis for this specialization?

 

The answer is that each cell expresses only a subset of all the genes in the genome. Only those genes necessary for that particular cell are expressed, and no others. The process of expressing genes is called transcription and involves the generation of messenger RNA from a DNA template.

Transcription is controlled by protein transcription factors and by small regulatory RNA molecules called microRNAs.

 

Whereas some transcription factors and microRNAs are broadly distributed throughout the body, others are restricted to only one organ or tissue. These regulatory molecules are called cellular identify factors, because they impart identity to the cell based upon the genes they turn on (or off).

My lab uses molecular and cellular techniques to study cellular identity factors that control development and homeostasis of pancreatic beta cells, the endocrine cells that secrete the hormone insulin after a meal. One protein transcription factor we study is Pdx-1, a factor critical for early pancreatic development as well as maintenance of the beta cell phenotype. Patients with mutations in Pdx-1 develop a form of the disease diabetes mellitus, due to the deficiency of insulin production.

 

My lab also studies a predominantly beta cell microRNA called miR-375. Studies suggest that animals lacking miR-375 develop abnormal Islets of Langerhans, the endocrine cells of the pancreas, which includes the beta cells. In mature beta cells, miR-375 appears to regulate insulin secretion.
The similar roles of Pdx-1 and miR-375 have led us to investigate how they may be interlinked.