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Alfred                         Ponticelli

Alfred S. Ponticelli PhD

Department of Biochemistry

Associate Professor

Specialty/Research Focus

Gene Expression; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Protein Function and Structure; Transcription and Translation

 
Professional Summary:

Our laboratory utilizes combined genetic, biochemical and molecular biological approaches to investigate the molecular mechanisms involved in the initiation and regulation of eukaryotic transcription. Previous work in our laboratory utilizing both the budding yeast Saccharomyces cerevisiae and human cells resulted in the identification and biochemical characterization of mutants of nuclear RNA polymerase II (RNAPII) and the general transcription factors TFIIB and TFIIF that coordinately affect transcription start site utilization and transcript elongation. These studies supported a model where yeast and human TFIIF induce global conformational changes in RNAPII that result in structural and functional changes in the polymerase active center.

Our current studies are focused on elucidating the mechanisms of kinetoplast transcription by the mitochondrial RNA polymerase of Trypanosoma brucei. T. brucei is a protozoan parasite that is the causative agent of African sleeping sickness (trypanosomiasis) in humans and nagana in animals. Procyclic trypanosomes growing in the midgut of the tsetse fly have a fully functional mitochondrion whereas trypanosomes in the mammalian bloodstream exhibit repressed mitochondrial function. The mitochondrial DNA in trypanosomes is unusual in its structure, comprising a highly catenated network of maxicircles and minicircles termed kinetoplast DNA (kDNA). Surprisingly, very little is known about the cis-acting elements and the trans-acting factors governing the transcription of maxicircles and minicircles. Our objective is to elucidate the mechanisms and regulation of T. brucei kDNA transcription with the ultimate goal of developing therapeutic agents.

Education and Training:
  • Postdoctoral Fellow, Harvard Medical School (1992)
  • PhD, Molecular Biology / Pathology, University of Washington (1988)
  • BS, Biochemistry, University of California at Los Angeles (1980)
Employment:
  • Associate Professor, Biochemistry, University at Buffalo (2000-present)
  • Assistant Professor, Biochemistry, University at Buffalo (1993–2000)
  • Assistant Professor, Molecular Biology, University of Wyoming (1992–1993)

Research Expertise:
  • Mechanisms of RNA synthesis in eukaryotes
Grants and Sponsored Research:
  • April 2006–April 2012
    Molecular Mechanisms of RNAPII Transcription
    National Institutes of Health
    Role: Principal Investigator
    $1,083,929
  • April 2000–December 2004
    Molecular Analysis of RNAPII Elongation Complexes
    National Institutes of Health
    Role: Principal Investigator
    $831,600
  • September 1999–August 2002
    Mechanisms of Yeast TFIIB Function in RNAPII Transcription Initiation.
    National Science Foundation
    Role: Principal Investigator
    $315,000
  • September 1993–August 1999
    Genetic and Biochemical Analysis of Yeast TFIIB
    NIH
    Role: Principal Investigator
    $529,250

Journal Articles:
  • Ishibashi T, Dangkulwanich M, Coello Y, Lionberger TA, Lubkowska L, Ponticelli AS, Kashlev M, Bustamante C. Transcription factors IIS and IIF enhance transcription efficiency by differentially modifying RNA polymerase pausing dynamics. Proc Natl Acad Sci U S A. 2014; 111(9).
  • Yang C, Ponticelli AS. Evidence that RNA polymerase II and not TFIIB is responsible for the difference in transcription initiation patterns between Saccharomyces cerevisiae and Schizosaccharomyces pombe. Nucleic Acids Res. 2012; 40(14).
  • Yang C, Khaperskyy DA, Hou M, Ponticelli AS. Improved methods for expression and purification of Saccharomyces cerevisiae TFIIF and TFIIH; identification of a functional Escherichia coli promoter and internal translation initiation within the N-terminal coding region of the TFIIF TFG1 subunit. Protein Expr Purif. 2010; 70(2).
  • Khaperskyy DA, Ammerman ML, Majovski RC, Ponticelli AS. Functions of Saccharomyces cerevisiae TFIIF during transcription start site utilization. Mol Cell Biol. 2008; 28(11).
  • Ponticelli AS. Unphosphorylated SR-like protein Npl3 stimulates RNA polymerase II elongation.. PLos ONE. 2008.
  • Fish RN, Ammerman ML, Davie JK, Lu BF, Pham C, Howe L, Ponticelli AS, Kane CM. Genetic interactions between TFIIF and TFIIS. Genetics. 2006; 173(4).
  • Majovski RC, Khaperskyy DA, Ghazy MA, Ponticelli AS. A functional role for the switch 2 region of yeast RNA polymerase II in transcription start site utilization and abortive initiation. J Biol Chem. 2005; 280(41).
  • Pal M, Ponticelli AS, Luse DS. The role of the transcription bubble and TFIIB in promoter clearance by RNA polymerase II. Mol Cell. 2005; 19(1).
  • Ghazy MA, Brodie SA, Ammerman ML, Ziegler LM, Ponticelli AS. Amino acid substitutions in yeast TFIIF confer upstream shifts in transcription initiation and altered interaction with RNA polymerase II. Mol Cell Biol. 2004; 24(24).
  • Ziegler LM, Khaperskyy DA, Ammerman ML, Ponticelli AS. Yeast RNA polymerase II lacking the Rpb9 subunit is impaired for interaction with transcription factor IIF.. J Biol Chem. 2003; 278(49).
  • Pardee TS, Ghazy MA, Ponticelli AS. Yeast and Human RNA polymerase II elongation complexes: evidence for functional differences and postinitiation recruitment of factors.. Eukaryot Cell. 2003; 2(2).
  • Faitar SL, Brodie SA, Ponticelli AS. Promoter-specific shifts in transcription initiation conferred by yeast TFIIB mutations are determined by the sequence in the immediate vicinity of the start sites.. Mol Cell Biol. 2001; 21(14).
  • Bradford PG, Maglich JM, Ponticelli AS, Kirkwood KL. The effect of bone morphogenetic protein-7 on the expression of type I inositol 1,4,5-trisphosphate receptor in G-292 osteosarcoma cells and primary osteoblast cultures.. Arch Oral Biol. 2000; 45(2).
  • Bangur CS, Faitar SL, Folster JP, Ponticelli AS. An interaction between the N-terminal region and the core domain of yeast TFIIB promotes the formation of TATA-binding protein-TFIIB-DNA complexes.. J Biol Chem. 1999; 274(33).
  • Pardee TS, Bangur CS, Ponticelli AS. The N-terminal region of yeast TFIIB contains two adjacent functional domains involved in stable RNA polymerase II binding and transcription start site selection.. J Biol Chem. 1998; 273(28).
  • Bangur CS, Pardee TS, Ponticelli AS. Mutational analysis of the D1/E1 core helices and the conserved N-terminal region of yeast transcription factor IIB (TFIIB): identification of an N-terminal mutant that stabilizes TATA-binding protein-TFIIB-DNA complexes.. Mol Cell Biol. 1997; 17(12).
  • Ponticelli AS, Pardee TS, Struhl K. The glutamine-rich activation domains of human Sp1 do not stimulate transcription in Saccharomyces cerevisiae.. Mol Cell Biol. 1995; 15(2).
  • Kelleher RJ, Flanagan PM, Chasman DI, Ponticelli AS, Struhl K, Kornberg RD. Yeast and human TFIIDs are interchangeable for the response to acidic transcriptional activators in vitro.. Genes Dev. 1992; 6(2).
  • Ponticelli AS, Smith GR. Chromosomal context dependence of a eukaryotic recombinational hot spot.. Proc Natl Acad Sci U S A. 1992; 89(1).
  • Cormack BP, Strubin M, Ponticelli AS, Struhl K. Functional differences between yeast and human TFIID are localized to the highly conserved region.. Cell. 1991; 65(2).
  • Ponticelli AS, Struhl K. Analysis of Saccharomyces cerevisiae his3 transcription in vitro: biochemical support for multiple mechanisms of transcription.. Mol Cell Biol. 1990; 10(6).
  • Ponticelli AS, Smith GR. Meiotic recombination-deficient mutants of Schizosaccharomyces pombe.. Genetics. 1989; 123(1).
  • Ponticelli AS, Sena EP, Smith GR. Genetic and physical analysis of the M26 recombination hotspot of Schizosaccharomyces pombe.. Genetics. 1988; 119(3).
  • Tsukamoto AS, Ponticelli A, Berk AJ, Gaynor RB. Genetic mapping of a major site of phosphorylation in adenovirus type 2 E1A proteins.. J Virol. 1986; 59(1).
  • Taylor AF, Schultz DW, Ponticelli AS, Smith GR. RecBC enzyme nicking at Chi sites during DNA unwinding: location and orientation-dependence of the cutting.. Cell. 1985; 41(1).
  • Ponticelli AS, Schultz DW, Taylor AF, Smith GR. Chi-dependent DNA strand cleavage by RecBC enzyme.. Cell. 1985; 41(1).
  • Konopka JB, Davis RL, Watanabe SM, Ponticelli AS, Schiff-Maker L, Rosenberg N, Witte ON. Only site-directed antibodies reactive with the highly conserved src-homologous region of the v-abl protein neutralize kinase activity.. J Virol. 1984; 51(1).
  • Smith GR, Amundsen SK, Chaudhury AM, Cheng KC, Ponticelli AS, Roberts CM, Schultz DW, Taylor AF. Roles of RecBC enzyme and chi sites in homologous recombination.. Cold Spring Harb Symp Quant Biol. 1984; 49.
  • Ponticelli AS, Whitlock CA, Rosenberg N, Witte ON. In vivo tyrosine phosphorylations of the Abelson virus transforming protein are absent in its normal cellular homolog.. Cell. 1982; 29(3).
  • Green N, Shinnick TM, Witte O, Ponticelli A, Sutcliffe JG, Lerner RA. Sequence-specific antibodies show that maturation of Moloney leukemia virus envelope polyprotein involves removal of a COOH-terminal peptide.. Proc Natl Acad Sci U S A. 1981; 78(10).
  • Witte ON, Ponticelli A, Gifford A, Baltimore D, Rosenberg N, Elder J. Phosphorylation of the Abelson murine leukemia virus transforming protein.. J Virol. 1981; 39(3).
See all (21 more)
Books and Book Chapters:
  • Ponticelli AS. Meiotic recombination in Schizosaccharomyces pombe: Genes, enzymes and sites.. 1990.
  • Ponticelli AS. Mechanism and control of homologous recombination.. 1986; 47.
  • Ponticelli AS. Studies of the path assembly of bacteriophage M13 coat protein into the Escherichia coli cytoplasmic membrane.. 1980.

Service Activities:
  • School of Medicine & Biomedical Sciences Faculty Council; Member (1997)

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Contact Information

649 Biomedical Research Building
Buffalo, NY 14214
Phone: (716) 829-2473
Email: asp@buffalo.edu


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