Research Expertise:

• : 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.
• : 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.

Research Centers:

• Center of Excellence in Bioinformatics and Life Sciences

UB 2020 Strategic Strengths:

• Health and Wellness Across the Lifespan
• Molecular Recognition in Biological Systems and Bioinformatics

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