Research Program: Genetic Mechanisms of Cancer
Associate Professor, Department of Genetics, Cell Biology and Development

conkl001@umn.edu
612-626-0445 — office
621-626-0638 —lab
Preferred method of contact: e-mail

Dr. Conklin received a B.A. degree from Barnard College, Columbia University in 1974 and a PhD in molecular biology from Tufts University School of Medicine 1982. She conducted postdoctoral research with Dr. Mark Groudine at the Fred Hutchinson Cancer Research Center in Seattle from 1982-1987. Since 1987 she has been on the faculty of the University of Minnesota, where she currently is an Associate Professor in the Department of Genetics, Cell Biology, and Development.

Research Interests

Nuceloli are not just for ribosomes anymore. Recently, it has become clear that nucleoli serve multiple functions, including receiving and responding to signals that regulate cell growth, the cell cycle, and the cellular response to stress. These activities necessitate that nucleoli have the capacity to rapidly modulate the activity of proteins required for essential cellular processes. A common mechanism to affect a rapid response is differential protein phosphorylation mediated by the concerted action of protein kinases and phosphatases. While a number of kinases have been identified that phosphorylate nucleolar proteins, little is known about the role of corresponding nucleolar phosphatases. Protein Phosphatase 1 (PP1) is an essential serine/threonine phosphatase required for most cellular processes. PP1 holoenzymes are composed of a PP1 catalytic subunit and one of over 50 different targeting subunits that dictate both the subcellular localization and the substrate specificity of the holoenzyme. Although enzymatically active PP1 is highly concentrated in nucleoli, no targeting subunit(s) have been identified that regulate either the localization or activity of PP1 in this critical subnuclear region. Our long-term goal is to understand the role of regulated protein phosphorylation-dephosphorylation in essential nucleolar processes. As a major advance towards this goal, we recently identified NOM1 (nucleolar protein with MIF4G domain 1) as the first nucleolar-specific PP1 targeting subunit. We (1) are identifying functionally significant nucleolar substrates targeted by the NOM1:PP1 complex (2) have demonstrated that NOM1 alters phosphorylation of proteins with critical nucleolar functions including the cellular proto-oncoproteins Myc and MSP58 (3) have demonstrated by RNAi that NOM1 is essential for cell growth and (4) are also using a tandem enrichment method combined with mass spectrometry to identify novel NOM1:PP1 targets and to define the role of NOM1 in essential nucleolar functions.

Selected Publications

Simmons HM, Oseth L, Nguyen P, Conklin KF, Hirsch BA. Cytogenetic and molecular heterogeneity of 7q36/12p13 rearrangements in childhood AML. Leukemia 2002;16:2408-2416.

Simmons HM, Ruis BL, Kapoor M, Hudacek AW, Conklin KF. Identification of NOM1, a nucleolar, eIF4A binding protein encoded within the chromosome 7q36 breakpoint region targeted in cases of pediatric acute myeloid leukemia.  Gene 2005;347:137-145.

Gunawardena SR, Ruis BL, Meyer JA, Kapoor M, Conklin KF. NOM1 targets protein phosphatase I to the nucleolus.  J Biol Chem. 2008;283:398-404.