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Biography

Mahender Mandala, PhD, is a Postdoctoral Associate in the Department of Rehabilitation Science and Technology, Instructor for Product Realization (RET) at the University of Pittsburgh, and a Research Associate at the Human Engineering Research Laboratories. He received his doctorate in Rehabilitation Science from the University of Pittsburgh (2016) where he worked on improving feedback design students receive using peers and crowds (read more here). In this direction he is developing a web-based peer review tool, titled Peerval (expected release Fall, 17). His work lies at the intersection of mechanical engineering, design, education, and cognitive science. He has several years of experience in product design and evaluation of assistive technology, and mixed-method research designs. His interests include improving participatory action design of assistive technology, creating tools and methodologies to improve collective innovation and collaborative design outcomes, and advocating the use of design-based learning in K-12. 

 

Karen Arndt
Office: (412) 624-6963
4249 Fifth Avenue
Pittsburgh, PA 15260
Education

Dr. Arndt received her Ph.D. in 1988 with Michael Chamberlin at the University of California at Berkeley, performed her postdoctoral studies with Fred Winston at Harvard Medical School, and joined the Department in 1994.

The multifunctional Paf1 complex associates with RNA pol II, promotes histone modifications coupled to active transcription, interacts with other transcription and chromatin factors, and regulates RNA 3’-end formation.|link=none|align=right|width=24|height=24]A critical question to ask, particularly in this genomic era, is how organisms interpret the vast amounts of information encoded in their genomes. The Arndt lab studies the first step in gene expression, the synthesis of mRNA by RNA polymerase II, with a focus on the mechanisms that regulate transcription in the chromatin environment of a eukaryotic cell.  The fundamental importance of understanding transcriptional regulation is evident from the large number of human developmental defects and diseases, including cancer and AIDS, that arise when cellular transcription factors are altered by mutation or commandeered by viral proteins.

The transcription cycle can be divided into three steps: (1) promoter recognition and initiation of RNA synthesis; (2) elongation of the growing RNA chain; and (3) termination.  Our current studies focus on the elongation and termination steps in the cycle.  In our research, we exploit a vast array of genetic, biochemical, and genomic tools uniquely available in the model eukaryote, Saccharomyces cerevisiae.  This simple yeast is an excellent model system for our studies because the proteins and mechanisms that regulate transcription have been highly conserved from yeast to man.

High resolution DNA microarray technology can be used to identify transcriptional patterns in different yeast strains.|link=none|align=left|width=24|height=24]During transcription elongation, RNA polymerase II encounters obstacles, notably nucleosomes, which block its path.  Eukaryotes express proteins that facilitate or impede polymerase movement by altering the chromatin template.  One of these proteins is the conserved Paf1 complex. The Paf1 complex associates with RNA polymerase II on the coding regions of transcribed genes, interacts with other highly conserved elongation factors, couples histone modification to transcription elongation, and controls the efficiency of transcription termination.  Thus, the Paf1 complex is a multifunctional regulator of gene expression that lies at the intersection between transcription elongation and chromatin modification.  Current projects in the lab are focused on:

  • The mechanisms by which the Paf1 complex regulates transcription elongation and events coupled to this process, especially RNA 3' end formation
  • The genes that are regulated by the Paf1 complex and how the Paf1 complex is recruited to these genes
  • The mechanisms by which the Rtf1 subunit of the complex controls histone modifications
  • The functions of the Cdc73 subunit of the Paf1 complex, a protein with tumor suppression activity in human cells
  • The cellular factors, including a novel ubiquitin protein-ligase, that protect the cell against the consequences of deregulated transcription
Recent Publications
  • Retchless, A.C. and J.G. Lawrence (2011) QUantification of codon selection for comparative bacterial genomics. BMC Genomics 12:374

  • A critical question to ask, particularly in this genomic era, is how organisms interpret the vast amounts of information encoded in their genomes. The Arndt lab studies the first step in gene expression, the synthesis of mRNA by RNA polymerase II, with a focus on the mechanisms that regulate transcription in the chromatin environment of a eukaryotic cell.  The fundamental importance of understanding transcriptional regulation is evident from the large number of human developmental defects and diseases, including cancer and AIDS, that arise when cellular transcription factors are altered by mutation or commandeered by viral proteins.

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