Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

DEPARTMENT OFMOLECULAR BIOLOGYCHAIRMANAndrei V. Gudkov, Ph.D.The Thomas Lord ChairSTAFFDonal S. Luse, Ph.D.Richard A. Padgett, Ph.D.Ganes C. Sen, Ph.D.Dennis W. Stacey, Ph.D.George R. Stark, Ph.D.ASSOCIATE STAFFMarian L. (Nikki) Harter, Ph.D.Kurt W. Runge, Ph.D.ASSISTANT STAFFPeter Chumakov, Ph.D.Kwaku Dayie, Ph.D.PROJECT SCIENTISTSMunna Agarwal, Ph.D.Mikhail Chernov, Ph.D.Katerina Gurova, Ph.D.Masahiro Hitomi, Ph.D.Eugene Kandel, Ph.D.Sean Kessler, Ph.D.Elena Komarova, Ph.D.Asoke Mal, Ph.D.Alo Ray, Ph.D.Girish Shukla, Ph.D.William Taylor, Ph.D.RESEARCH ASSOCIATESLyudmila Burdelya, Ph.D.Yang Guo, Ph.D.Julia Kichina, Ph.D.Mahadeb Pal, Ph.D.Subramania Sanker, Ph.D.Saumendra Sarkar, Ph.D.Fulvia Terenzi, Ph.D.Ke Yang, Ph.D.102Targeting the Molecular Basis of DiseaseThe Department of Molecular Biology wasestablished in 1987 with the mission tobuild the programmatic and methodologicalinfrastructure of molecular biology within theResearch Institute and to stimulate research onthe structure, regulation and mechanisms ofactivity of viral and cellular genes. During thistime, the Department has developed into a strongacademic union of nationally recognized expertsrepresenting a broad spectrum of disciplines. Itmaintains the spirit of collegiality and mutualsupport, has a solid technical infrastructure and isefficiently run by an experienced administrativeteam. Ongoing research programs cover thefollowing areas.Understanding the molecular mechanismsof stress-, cytokine-, and oncogene-mediatedThe Department of Molecular BiologyAndrei Gudkov, Ph.D., D.Sci.signal transduction remains a major area ofresearch within the Department. George Stark’sand Ganes Sen’s laboratories have a long-standinginterest in deciphering mechanisms by whichinterferon (IFN)-mediated signaling occur inmammalian cells via activation of various signaltransducers, resulting in changes in gene expression.Stark’s team, in addition, is working onunderstanding the mechanisms of activation ofthe p53 tumor suppressor protein by variousstresses and its effects on cellular growthregulation. Sen’s laboratory is involved indetermining functional characteristics of severalIFN-induced proteins as well as signaling initiatedby double-stranded RNA. Another area ofinterest is the analysis of specific physiologicalroles of different isoforms of angiotensinconvertingenzymes with tissuespecific expression. Dennis Stacey’slaboratory is focused on the role ofoncogene ras-mediated signaling andtopoisomerase II expression in controlof cell cycle and cell response tochemotherapeutic drugs. The groupdevelops and applies unique experimentalapproaches to the analysis ofthe cell cycle allowing revision ofestablished dogmas in this highlycompetitive field. Nikki Harter’slaboratory is working on understandingthe molecular mechanics of cellgrowth and differentiation byoncoprotein E1A and myogenictranscription factor MyoD, bothcontributing to understanding themolecular mechanisms of oncogenesis.The laboratories of two staffmembers are involved in understandingmost basic mechanisms of cellularRNA synthesis and processing. DonalLuse leads a team that studiestranscription by RNA polymerase IIwith specific focus on promoterclearance and regulation of initialsteps of transcript elongation. RichardPadgett primarily focuses his studieson the molecular mechanisms of RNAsplicing, including the chemistry ofthis process, identification of cellularfactors involved in control of RNAsplicing and evolution of splicingmachinery.Kurt Runge continues work onthe replication and maintenance oftelomeres, the physical ends ofeukaryotic chromosomes, usingbudding yeast as a model organism.Besides understanding telomere structure andfunction, his work provides insights into themechanisms of cellular aging, and the control ofContinued on Page 103