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OFFICE LOCATIONS
Office
119 Farber Hall
Buffalo NY, 14214-3001
 View map |
DESCRIPTION OF INTERESTS
| We are working on the Nuclear Factor I and T-box families of transcription factors. We are investigating their roles in development and analysis of their "regulomes", that is, all the genes regulated by the specific transcription factor. |
SPECIALTIES
Bioinformatics
Cell growth, development and Virology differentiation
Molecular and Cellular Biology
Molecular basis of disease and Parasitology
Molecular genetics
Neurobiology
Regulation of gene expression
Regulation of transcription and translation |
EDUCATION
| 1982 |
Doctor of Philosophy, Physiology
Harvard University
Ryan Foundation Fellow |
| 1977 |
MS, Biochemistry
Virginia Polytechnic Institute and State University
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| 1975 |
BS, Biochemistry
Virginia Polytechnic Institute and State University
With Honors
Phi Eta Sigma |
EXPERTISE
NFI transcription factors
Role of Nuclear Factor I transcription/replication proteins in mammalian and nematode development.
The goal of our laboratory is to gain a better understanding of how proteins that interact with DNA regulate RNA transcription, DNA replication and metazoan development. Our focus is on the structure and function of the Nuclear Factor I (NFI) family of site-specific DNA binding proteins. In vertebrates, NFI family members function in both the replication of viral DNA and the transcription of viral and cellular genes. We are currently analyzing the role of the NFI gene family in both vertebrate and C. elegans development.
Studies on NFI can be divided into two major themes: (1) biochemical analysis of NFI protein structure and function and (2) molecular genetic studies on NFI's role in cell growth, differentiation and development.
(1) The DNA-binding domain of NFI differs from those found in other well characterized DNA-binding proteins. Four major questions being addressed in the laboratory are: What is the structure of the NFI DNA-binding domain? How does NFI recognize and interact with DNA? Does NFI change the structure of DNA when it binds? What proteins interact with NFI to stimulate RNA transcription and/or DNA replication?
We have shown that the NFI-C protein represses the glucocorticoid-dependent expression of the MMTV promoter. This repression can be overcome by overexpression of the co-activator proteins CBP, p300 or SRC-1, suggesting a role of these co-activators in MMTV expression. Surprisingly, NFI-C doesn't repress progesterone stimulation of MMTV. We are currently working out the biochemical mechanism for this repression by NFI-C and the roles of co-activators, histone acetylase activity and chromatin remodeling activity in the process.
(2) Using the mouse embryonic stem cell (ES cell) system and human leukemic cells, the role of NFI family members during cell differentiation is being studied. We showed previously that the forms of NFI present in ES and leukemic cells change during the differentiation of the cells in vitro. Currently we are asking the questions: By what mechanism does the form of NFI change during differentiation? How does the expression of different NFI family members affect pathways of differentiation? Is the expression of specific NFI family members required for the synthesis of specific classes of proteins in terminally differentiated cell types? What is the phenotype of mutant mice deficient in one or more NFI gene?
The NFI-A deficient mouse we generated (Nfia-) has major neurological defects including agenesis of the corpus callosum and hydrocephalus. We're now studying the biochemical pathways leading to these developmental defects with the goal of determining how loss of a single transcription factor results in major neuroanatomical changes. We're focusing on whether loss of NFI-A causes changes in: 1) cell proliferation or death, 2) cell migration or differentiation, 3) axonal outgrowth, 4) axonal pathfinding, 5) glial cell differentiation and 6) patterns of neuronal or glial cell gene expression.
While all vertebrates examined contain 4 highly conserved NFI genes (NFI-A, -B, -C and -X), the nematode Caenorhabditis elegans has only a single NFI gene (nfi-1). Unlike the case in vertebrates, where all 4 NFI genes are expressed in many tissues during both embryogenesis and throughout adult life, the C. elegans nfi-1 gene is expressed primarily during embryogenesis. In collaboration with Yuji Kohara we've identified where nfi-1 mRNA is expressed in C. elegans and are assessing the phenotype of worms deficient in the nfi-1 gene product. By comparing the function of NFI in worms and mice, we are asking how NFI-dependent developmental pathways have been conserved through over 500M years of evolution. |
PUBLICATIONS
| Park JC, Herr Y, Kim HJ, Gronostajski RM, Cho MI; Nfic gene disruption inhibits differentiation of odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice; J Periodontol; 2007; 78; 1795-1802 |
| Ling G, Hauer CR, Gronostajski RM, Pentecost BT, Ding X; Transcriptional Regulation of Rat CYP2A3 by Nuclear Factor 1: IDENTIFICATION OF A NOVEL NFI-A ISOFORM, AND EVIDENCE FOR TISSUE-SELECTIVE INTERACTION OF NFI WITH THE CYP2A3 PROMOTER IN VIVO.; J Biol Chem; 2004 Jul; 279(27); 27888-27895 |
| Bachurski CJ, Yang GH, Currier TA, Gronostajski RM, Hong D; Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant protein C transcription.; Mol Cell Biol; 2003 Dec; 23(24); 9014-9024 |
| Messam CA, Hou J, Gronostajski RM, Major EO; Lineage pathway of human brain progenitor cells identified by JC virus susceptibility.; Ann Neurol; 2003 May; 53(5); 636-646 |
| Kido K, Bannert H, Gronostajski RM, Flügel RM; Bel1-mediated transactivation of the spumaretroviral internal promoter is repressed by nuclear factor I.; J Biol Chem; 2003 Apr; 278(14); 11836-11842 |
| Murtagh J, Martin F, Gronostajski RM; The Nuclear Factor I (NFI) gene family in mammary gland development and function.; J Mammary Gland Biol Neoplasia; 2003 Apr; 8(2); 241-254 |
| Steele-Perkins G, Butz KG, Lyons GE, Zeichner-David M, Kim HJ, Cho MI, Gronostajski RM; Essential role for NFI-C/CTF transcription-replication factor in tooth root development.; Mol Cell Biol; 2003 Feb; 23(3); 1075-1084 |
| Pan L, Glenn ST, Jones CA, Gronostajski RM, Gross KW; Regulation of renin enhancer activity by nuclear factor I and Sp1/Sp3.; Biochim Biophys Acta; 2003 Feb; 1625(3); 280-290 |
| Shu T, Butz KG, Plachez C, Gronostajski RM, Richards LJ; Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice.; J Neurosci; 2003 Jan; 23(1); 203-212 |
| Richard Gronostajski; Nuclear Factor I; Encyclopedia of Molecular Medicine; 2002 Jan; 4; 2291-2292 |
| Gronostajski R; Nuclear Factors; Encyc. Molec. Med.; 2002; |
| Richard Gronostajski; Nuclear Factors; Encyclopedia of Molecular Medicine; 2002 Jan; 4; 2290-2291 |
| Mukhopadhyay SS, Wyszomierski SL, Gronostajski RM, Rosen JM; Differential interactions of specific nuclear factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene transcription.; Mol Cell Biol; 2001 Oct; 21(20); 6859-6869 |
| Majumder S, Ghoshal K, Gronostajski RM, Jacob ST; Downregulation of constitutive and heavy metal-induced metallothionein-I expression by nuclear factor I.; Gene Expr; 2001 Sep; 9(4-5); 203-215 |
| Sinha S, Abraham S, Gronostajski RM, Campbell CE; Differential DNA binding and transcription modulation by three T-box proteins, T, TBX1 and TBX2.; Gene; 2000 Nov; 258(1-2); 15-29 |
| Gronostajski RM; Roles of the NFI/CTF gene family in transcription and development.; Gene; 2000 May; 249(1-2); 31-45 |
| Behrens M, Venkatraman G, Gronostajski RM, Reed RR, Margolis FL; NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression.; Eur J Neurosci; 2000 Apr; 12(4); 1372-1384 |
| das Neves L, Duchala CS, Tolentino-Silva F, Haxhiu MA, Colmenares C, Macklin WB, Campbell CE, Butz KG, Gronostajski RM, Godinho F; Disruption of the murine nuclear factor I-A gene (Nfia) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum.; Proc Natl Acad Sci U S A; 1999 Oct; 96(21); 11946-11951 |
| Baumeister H, Gronostajski RM, Lyons GE, Margolis FL; Identification of NFI-binding sites and cloning of NFI-cDNAs suggest a regulatory role for NFI transcription factors in olfactory neuron gene expression.; Brain Res Mol Brain Res; 1999 Sep; 72(1); 65-79 |
| Fletcher CF, Jenkins NA, Copeland NG, Chaudhry AZ, Gronostajski RM; Exon structure of the nuclear factor I DNA-binding domain from C. elegans to mammals.; Mamm Genome; 1999 Apr; 10(4); 390-396 |
| Leahy P, Crawford DR, Grossman G, Gronostajski RM, Hanson RW; CREB binding protein coordinates the function of multiple transcription factors including nuclear factor I to regulate phosphoenolpyruvate carboxykinase (GTP) gene transcription.; J Biol Chem; 1999 Mar; 274(13); 8813-8822 |
| Chaudhry AZ, Vitullo AD, Gronostajski RM; Nuclear factor I-mediated repression of the mouse mammary tumor virus promoter is abrogated by the coactivators p300/CBP and SRC-1.; J Biol Chem; 1999 Mar; 274(11); 7072-7081 |
| Chaudhry AZ, Vitullo AD, Gronostajski RM; Nuclear factor I (NFI) isoforms differentially activate simple versus complex NFI-responsive promoters.; J Biol Chem; 1998 Jul; 273(29); 18538-18546 |
| Crawford DR, Leahy P, Hu CY, Chaudhry A, Gronostajski R, Grossman G, Woods J, Hakimi P, Roesler WJ, Hanson RW; Nuclear factor I regulates expression of the gene for phosphoenolpyruvate carboxykinase (GTP).; J Biol Chem; 1998 May; 273(22); 13387-13390 |
| Bandyopadhyay S, Starke DW, Mieyal JJ, Gronostajski RM; Thioltransferase (glutaredoxin) reactivates the DNA-binding activity of oxidation-inactivated nuclear factor I.; J Biol Chem; 1998 Jan; 273(1); 392-397 |
| Chaudhry AZ, Lyons GE, Gronostajski RM; Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development.; Dev Dyn; 1997 Mar; 208(3); 313-325 |
| Kulkarni S, Gronostajski RM; Altered expression of the developmentally regulated NFI gene family during phorbol ester-induced differentiation of human leukemic cells.; Cell Growth Differ; 1996 Apr; 7(4); 501-510 |
| Bandyopadhyay S, Gronostajski RM; Identification of a conserved oxidation-sensitive cysteine residue in the NFI family of DNA-binding proteins.; J Biol Chem; 1994 Nov; 269(47); 29949-29955 |
| Novak A, Goyal N, Gronostajski RM; Four conserved cysteine residues are required for the DNA binding activity of nuclear factor I.; J Biol Chem; 1992 Jun; 267(18); 12986-12990 |
| Knox JJ, Rebstein PJ, Manoukian A, Gronostajski RM; In vivo stimulation of a chimeric promoter by binding sites for nuclear factor I.; Mol Cell Biol; 1991 Jun; 11(6); 2946-2951 |
| Goyal N, Knox J, Gronostajski RM; Analysis of multiple forms of nuclear factor I in human and murine cell lines.; Mol Cell Biol; 1990 Mar; 10(3); 1041-1048 |
| Gronostajski RM, Knox J, Berry D, Miyamoto NG; Stimulation of transcription in vitro by binding sites for nuclear factor I.; Nucleic Acids Res; 1988 Mar; 16(5); 2087-2098 |
| Gronostajski RM; Site-specific DNA binding of nuclear factor I: effect of the spacer region.; Nucleic Acids Res; 1987 Jul; 15(14); 5545-5559 |
| Gronostajski RM; Analysis of nuclear factor I binding to DNA using degenerate oligonucleotides.; Nucleic Acids Res; 1986 Nov; 14(22); 9117-9132 |
| Gronostajski RM, Sadowski PD; The FLP recombinase of the Saccharomyces cerevisiae 2 microns plasmid attaches covalently to DNA via a phosphotyrosyl linkage.; Mol Cell Biol; 1985 Nov; 5(11); 3274-3279 |
| Gronostajski RM, Sadowski PD; Determination of DNA sequences essential for FLP-mediated recombination by a novel method.; J Biol Chem; 1985 Oct; 260(22); 12320-12327 |
| Gronostajski RM, Sadowski PD; The FLP protein of the 2-micron plasmid of yeast. Inter- and intramolecular reactions.; J Biol Chem; 1985 Oct; 260(22); 12328-12335 |
| Babineau D, Vetter D, Andrews BJ, Gronostajski RM, Proteau GA, Beatty LG, Sadowski PD; The FLP protein of the 2-micron plasmid of yeast. Purification of the protein from Escherichia coli cells expressing the cloned FLP gene.; J Biol Chem; 1985 Oct; 260(22); 12313-12319 |
| Gronostajski RM, Adhya S, Nagata K, Guggenheimer RA, Hurwitz J; Site-specific DNA binding of nuclear factor I: analyses of cellular binding sites.; Mol Cell Biol; 1985 May; 5(5); 964-971 |
| Gronostajski RM, Pardee AB, Goldberg AL; The ATP dependence of the degradation of short- and long-lived proteins in growing fibroblasts.; J Biol Chem; 1985 Mar; 260(6); 3344-3349 |
| Gronostajski RM, Goldberg AL, Pardee AB; The role of increased proteolysis in the atrophy and arrest of proliferation in serum-deprived fibroblasts.; J Cell Physiol; 1984 Oct; 121(1); 189-198 |
| Field J, Gronostajski RM, Hurwitz J; Properties of the adenovirus DNA polymerase.; J Biol Chem; 1984 Aug; 259(15); 9487-9495 |
| Gronostajski RM, Field J, Hurwitz J; Purification of a primase activity associated with DNA polymerase alpha from HeLa cells.; J Biol Chem; 1984 Aug; 259(15); 9479-9486 |
| Gronostajski RM, Nagata K, Hurwitz J; Isolation of human DNA sequences that bind to nuclear factor I, a host protein involved in adenovirus DNA replication.; Proc Natl Acad Sci U S A; 1984 Jul; 81(13); 4013-4017 |
| Gronostajski RM, Pardee AB; Protein degradation in 3T3 cells and tumorigenic transformed 3T3 cells.; J Cell Physiol; 1984 Apr; 119(1); 127-132 |
| Gronostajski RM, Goldberg AL, Pardee AB; Energy requirement for degradation of tumor-associated protein p53.; Mol Cell Biol; 1984 Mar; 4(3); 442-448 |
| Turner KJ, Gronostajski RM, Schmidt RR; Regulation of initial rate of induction of nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase during the cell cycle of synchronous Chlorella.; J Bacteriol; 1978 Jun; 134(3); 1013-1019 |
| Gronostajski RM, Yeung AT, Schmidt RR; Purification and properties of the inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase from Chlorella sorokiniana.; J Bacteriol; 1978 May; 134(2); 621-628 |
| Israel, D. W., Gronostajski R. M., Yeung, A. T., Schmidt, R. R.; Regulation of glutamate dehydrogenase induction and turnover during the cell cycle of the eukaryote Chlorella.; Cell Cycle Regulation; 1978; |
| Israel DW, Gronostajski RM, Yeung AT, Schmidt RR; Regulation of accumulation and turnover of an inducible glutamate dehydrogenase in synchronous cultures of Chlorella.; J Bacteriol; 1977 May; 130(2); 793-804 |
| Majumder S, Ghoshal K, Gronostajski RM, Jacob ST; Downregulation of constitutive and heavy metal-induced metallothionein-I expression by nuclear factor I.; Gene Expr; 9(4-5); 203-215 |
| Friefeld BR, Lichy JH, Field J, Gronostajski RM, Guggenheimer RA, Krevolin MD, Nagata K, Hurwitz J, Horwitz MS; The in vitro replication of adenovirus DNA.; Curr Top Microbiol Immunol; 110; 221-255 |
GRANTS
April 2002 to March 2005
Novel Genes expressed during Kidney Development
NIDDK
Richard Gronostajski, Christine Campbell
$215,858
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November 2001 to March 2004
Novel Genes Expressed during Kidney Development
NIDDK
Christine Campbell
$259,593
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to August 2005
Genes & Proteins Needed for NFI-regulated Transcription
NIDDK
Richard Gronostajski
$175,000
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