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Richard                        Gronostajski

Richard M. Gronostajski PhD

Department of Biochemistry

Professor of Biochemistry; Director of the Genetics, Genomics & Bioinformatics Graduate Program; Director, Western New York Stem Cell Culture and Analysis Cetner (WNYSTEM)

Specialty/Research Focus

Bioinformatics; Cell growth, differentiation and development; Gene Expression; Genomics and proteomics; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Neurobiology; Stem Cells; Transgenic organisms

 
Professional Summary:

My research goal is to gain a better understanding of how proteins that interact with DNA regulate RNA transcription, DNA replication and metazoan development. I mentor undergraduate and graduate students in my lab; we focus on the structure and function of the Nuclear Factor I (NFI) family of site-specific DNA binding proteins, and we are investigating their roles in development. Our work has been made possible by our development of loss-of-function mutations of the NFI genes in the mouse and C. elegans.

We are addressing four major questions in my laboratory and in collaboration with a number of talented collaborators: 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?

These research questions are explored in my lab through two major projects focused on the role of NFIB in lung development and the role of NFIX in brain development.

When NFIB is deleted from the germline of mice the animals die at birth because their lungs fail to mature normally. This provides a good model for the problems that occur with premature infants, whose lungs also fail to mature normally. We are using this model to determine how NFIB promotes lung maturation with the goal of being able to stimulate this process in premature infants.

In our NFIX knockout animals, the brains of the animals are actually larger than normal and contain large numbers of cells in an area known to be the site of postnatal neurogenesis. We have evidence that NFIX may regulate the proliferation and differentiation of neural stem cells, which produce new neurons throughout adult life. Our aim is to understand the specific target genes that NFIX regulates in the adult brain to control this process of neurogenesis.

Education and Training:
  • PhD, Physiology, Harvard University (1982)
  • MS, Biochemistry, Virginia Polytechnic Institute and State University (1977)
  • BS, Biochemistry, Virginia Polytechnic Institute and State University, With Honors (1975)
Employment:
  • Director: Genetics, Genomics & Bioinformatics, Genetics, Genomics and Bioinformatics, University at Buffalo (2013-present)
  • Professor, Biochemistry, 140 Farber Hall, University at Buffalo (2001-present)
  • Associate Professor, Biochemistry, Case Western Reserve University, School of Medicine (1992–2001)
  • Assistant Professor, Medical Biophysics, Ontario Cancer Institute, University of Toronto, Canada (1985–1992)

Research Expertise:
  • : The goal of our laboratory is to gain a better understanding of how proteins that interact with DNA regulate RNA transcription 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.
Research Centers:
  • Center of Excellence in Bioinformatics and Life Sciences
UB 2020 Strategic Strengths:
  • Molecular Recognition in Biological Systems and Bioinformatics
  • Health and Wellness Across the Lifespan
Grants and Sponsored Research:
  • September 2016–August 2021
    Stem Cells in Regenerative Medicine (SCiRM)
    NYSTEM (NYSDOH)
    Role: Contributor
    $1,750,000
  • December 2015–November 2018
    Role of Nfi genes in neural stem cell homeostasis
    NYSTEM (NYSDOH)
    Role: Principal Investigator
    $1,073,067
  • August 2011–July 2015
    WNYSTEM, Western New York Stem Cell Culture and Analysis Center
    NYSTEM
    Role: Principal Investigator
    $3,564,599
  • September 2010–August 2013
    Role of Nfix in Neural Stem Cells and glioblastoma
    NYSTEM
    Role: Co-Investigator
    $1,061,683
  • March 2007–February 2013
    Role of NFI genes in mouse lung development
    NIH
    Role: Principal Investigator
    $1,981,250
  • –August 2005
    Genes & Proteins Needed for NFI-regulated Transcription
    NIDDK
    Role: Principal Investigator
    $175,000
  • April 2002–March 2005
    Novel Genes expressed during Kidney Development
    NIDDK
    Role: Principal Investigator
    $215,858
  • November 2001–March 2004
    Novel Genes Expressed during Kidney Development
    NIDDK
    Role: Principal Investigator
    $259,593

Journal Articles:
See all (85 more)
Books and Book Chapters:
  • Richard Gronostajski. Nuclear Factors. Encyclopedia of Molecular Medicine. 2002; 4.
  • Richard Gronostajski. Nuclear Factor I. Encyclopedia of Molecular Medicine. 2002; 4.
  • Gronostajski R. Nuclear Factors. Encyc. Molec. Med.. 2002.
  • 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.

Professional Memberships:
  • ISSCR; International Society for Stem Cell Research (2013–present)
  • SDB; Society for Developmental Biology (2010–present)
  • ASM; American Society for Microbiology (2003–2005)
  • ASBMB; American Society for Biochemistry and Molecular BIology (1990–2004)
Presentations:
  • "NFIB: A governor of epithelial-melanocyte stem cell behaviour in a shared niche" ISSCR, ISSCR (2013)
  • "NFIX REGULATES THE FATE OF NEURAL STEM CELLS IN POSTNATAL MOUSE BRAIN" NYSTEM 2013, NYSTEM (2013)
  • "Nuclear Factor I (NFI) transcription factors: a small family that does big things in brain development." Queensland Brain Institute, University of Queensland (2013)
  • "Roles for Nuclear Factor I (NFI) transcription factors in lung, muscle, tooth and skin development." Institute for Molecular Bioscience, University of Queensland (2013)
  • "Regenerative Medicine: A New Opportunity for Blood Center Diversification?" America's Blood Centers, America's Blood Centers (2012)
  • "WNYSTEM: Western New York Stem Cell Culture and Analysis Center" NYSTEM Annual Meeting, NYSTEM (2012)
  • "Multiple roles for Nuclear Factor I (NFI) transcription factors in the development of lung, brain, gut and other organ systems" Vanderbilt University, Vanderbilt University, Developmental Biology (2011)
  • "Multiple roles for Nuclear Factor I (NFI) transcription factors in the development of brain, lung and other organ systems" NIH (2011)
  • "Multiple roles for Nuclear Factor I (NFI) transcription factors in the development of brain, lung and other organ systems" Virginia Bioinformatics Institute, Virginia Tech (2011)
  • "Multiple roles for the Nuclear Factor I (NFI) transcription factor family in metazoan development" NIH, NID (2003)
Service Activities:
  • School of Medicine & Biomedical Sciences Faculty Council; Member (2003–2009)
  • Chair, Faculty Advisory Committee MRBSB, UB2020; Chair (2013–present)
  • Director: Genetics, Genomics & Bioinformatics Graduate Program; Director (2013–present)
  • Member Faculty Practice Management Plan Governing Board; Member (2013–present)
  • Director Western New York Stem Cell Culture and Analysis Center; Director (2011–present)
  • Member Empire State Stem Cell Board (ESSCB); Member (2011–present)
  • Member Board of Directors UB Associates; Board of Directors (2009–2010)
  • Standing Committee for Facilities Planning and Budget; Chair (2008–2009)
  • Member Faculty Practice Management Plan Governing Board; Member (2008–2010)
  • Member Faculty Advisory Committee UB2020 Molecular Recognition in Biological Systems/Bioinformatics Strategic Strength; Member (2005–2013)
  • Founder Developmental Genomics Focus of Excellence; Director (2004–present)
  • Member of Faculty Council 2003-2009; Member (2003–2009)
  • Member Search Committee Bioinformatics; Committee Member (2003–2006)
  • Chair of session in Frontiers of Bioinformatics 2003; Panel Member (2003)
  • Member IGPBS steering committee; Member (2003–2007)
  • Member Graduate Admissions committee; Member (2003–2007)
  • Member IRCAF review panel 2003; Ad Hoc Reviewer (2003)
  • Co-organizer of Biochemistry Annual Research Day; Organizing Committee Member (2003–2008)
  • Member MSTP Admissions/Steering Committee 2003-present; Member (2003–present)
  • Member IFR Committee 2001-present; Member (2001–present)

Clinical Specialties:
Clinical Offices:
Insurance Accepted:


Contact Information

Center of Excellence in Bioinformatics and Life Sciences
701 Ellicott St.
Room 3-303
Buffalo, NY 14203
Phone: (716) 829-3471
Fax: (716) 849-6655
Email: rgron@buffalo.edu


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