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Alexei Tulin, PhD

Alexei Tulin, PhD
About

Associate Professor

Research Program

The PARP protein localization in salivary gland polytene chromosomes is shown
Figure 1
Poly(ADP-ribose) turnover
PARP mutation drastically alters chromatin structure
PARP activity is restricted to nucleolus and puffs
Localization of PARP and PARG proteins in a single nucleus
PARP protein activity cycle
PARP protein localizes into Cajal body in Parg mutants
A model of proteins delivery of Cajal body by PARP protein shuttling
Figure 3
Colocalization of pADPr and hnRNP proteins in puffs
Poly(ADP-ribosyl)ation inhibits hnRNP binding to RNA
The model for the splicing modulation by hnRNP poly(ADP-ribosyl)ation
PARP is required for nucleolar function
Figure 2
The PARP protein localization in salivary gland polytene chromosomes is shown

 

Education, Training & Credentials

Educational Background

  • PhD, Molecular Biology, Moscow State University, Moscow, Russia, 1997
  • MS, Molecular Biology, Moscow State University, Moscow, Russia, 1994
  • BS, Biology, Moscow State University, Moscow, Russia, 1993
Research Profile

Research Program

Research Interests

The principal focus of our research is on understanding functions of poly(ADP-ribose) polymerase 1 (PARP1) and the mechanisms of chromatin regulation by protein-poly(ADP-ribosyl)ation.  We have recently demonstrated that poly(ADP-ribose) polymerase 1 (PARP1) and poly(ADP-ribose) glycohydrolase (PARG) perform a number of vital previously unrecognized functions in a number of cellular processes (Tulin et al. 2002;  Tulin et al. 2006).  Distributed evenly along chromatin (Figure 1AB) and enriched in nucleoli (Figure 1AB), PARP1 is responsible for rapid local chromatin decondensation (loosening) (Figure 1), which is required for transcriptional activation of many genes within specific chromatin blocks (Tulin & Spradling 2003).  Poly(ADP-ribosyl)ation is also involved in heterochromatin formation and the initiation and maintenance of nucleoli (Figure 1D).

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Lab Overview

Role of Poly(ADP-ribose)Polymerase in Chromatin Programming and Transcription

Tulin Lab

Developmentally regulated gene expression in multicellular eukaryotes requires the formation of dynamic tissue-specific chromatin structures that participate in activating certain genes and silencing others (Wolffe, Essays Biochem. 37:45, 2001). Furthermore, during an organism’s lifetime the established pattern of chromatin needs to be quickly reprogrammed in a response to environmental or hormonal signals (Thummel, Insect Biochem. Mol. Biol. 32:113, 2002). It has become increasingly clear that key aspects of chromatin structure and gene transcriptional activity are determined by a specific modification of histones (Elgin and Workman, Curr Opin Genet Dev. 12: 127, 2002; Fischle et al., Nature. 425:475, 2003).

Despite this exciting progress there remains much to be learned about how chromatin is programmed and how active or inactive domains are maintained. Our studies of the abundant nuclear enzyme poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) demonstrated that it plays novel and previously unknown roles in many of these processes. Distributed evenly along chromatin PARP is responsible for rapid local chromatin decondensation (loosening), which is required for transcriptional activation of many genes within particular chromatin blocks. Previously we have demonstrated that poly(ADP-ribosyl)ation is also involved in heterochromatin formation, the initiation and maintenance of nucleoli and telomere metabolism. The presence of several PARP-related proteins in mammals complicates the analysis and interpretation of results. Fortunately, only a single PARP gene is present in the Drosophila genome, making this animal an invaluable model system to study PARP function. Using Drosophila we study the molecular mechanisms of PARP activation, its action on chromatin and the interaction of PARP with other components of the chromatin remodeling machinery and transcriptional apparatus. 

People

Yingbiao Ji, PhD

Postdoctoral Associate

Room: R362
215-728-2775

Ernest Boamah, PhD

Postdoctoral Fellow (NIH)

Room: R362
215-728-2775

Elena Kotova, MS

Technical Specialist

Room: R362
215-728-2775

Colin James Thomas, BS

Scientific Technician I

Room: R357
215-728-2775
 
Former Members
  • Mikael Garabedian, BS, Scientific Technician I 
  • Niraj Lodhi, PhD, Postdoctoral Associate
  • Aaron Dan Pinnola, BS, Scientific Technician I
  • Natalia M Naumova, PhD, Postdoctoral Associate
  • Ammini K Menon, BS, Scientific Technician I
 
Positions Available

Postdoctoral and Technician

Two postdoctoral/technician research positions are available. Researchers will study the molecular mechanisms of the chromatin remodeling and transcriptional activation using model organisms (Drosophila melanogaster and/or mouse) as well as in vitro assays. Applicants should have a Ph.D. in molecular biology, molecular genetics, biochemistry, or a related field with 0-3 years postdoctoral research experience. Experience in confocal microscopy, live-cell imaging (FRAP, FRET) and genomics/proteomics would be helpful. The choice of the project will be discussed with a candidate during the interview.

Alexei Tulin, PhD
Epigenetics and Progenitor Cells Program
Fox Chase Cancer Center
333 Cottman Ave. R362,
Philadelphia, PA 19111

E-mail: Alexei.Tulin@fccc.edu

Publications

Selected Publications

Lodhi N, Kossenkov A, Tulin AV.  2014. Bookmarking promoters in mitotic chromatin: Poly(ADP-ribose)Polymerase-1 as an epigenetic mark.  Nucleic Acids Res. 42(11): 7028-7038. PubMed

Thomas CJ, Kotova E, Andrake M, Adolf-Bryfogle J, Glaser R, Regnard C, Tulin AV.  2014. Kinase-mediated changes in nucleosome conformation trigger chromatin decondensation via poly-ADP-ribosylation.  Mol Cell.53: 831–842. PubMed

Thomas C, Tulin AV.  2013. Poly-ADP-Ribose Polymerase: Machinery for Nuclear Processes.  Mol Aspects Med.  34(6): 1124-1137. PubMed

Ji Y, Tulin AV.  2012. Poly(ADP-ribose) controls DE-cadherin-dependent stem cell maintenance and oocyte localization. Nat Commun.. 3: 760.  Doi:10.1038/ncomms1759. PubMed

MBoamah EK, Kotova E, Garabedian M, Jarnik M,Tulin AV. 2012.  Poly(ADP-ribose) Polymerase 1 (PARP-1) regulates ribosomal biogenesis in Drosophila nucleoli.  PLoS Genetics. 8(1):e1002442.  PMCID: PMC3252306. PubMed

Additional Publications

PubMed

Tulin: Poly(ADP Ribose) Polymerase

Edited by Alexei Tulin: Poly(ADP Ribose) Polymerase (Methods and Protocols)
Purchase it on Amazon.

This Fox Chase professor participates in the Undergraduate Summer Research Fellowship
Learn more about Research Volunteering.