Anthony N Imbalzano PhD
|Institution||University of Massachusetts Medical School|
|Department||Cell and Developmental Biology|
|Address||University of Massachusetts Medical School|
55 Lake Avenue North
Worcester MA 01655
|Institution||UMMS - Graduate School of Biomedical Sciences|
|Institution||UMMS - Graduate School of Biomedical Sciences|
|Department||Interdisciplinary Graduate Program|
B.A. (cum laude), University of Pennsylvania, 1986
Ph.D., Harvard University, 1991
Post-doctoral Fellow, Massachusetts General Hospital, 1991-1996
Assistant Professor, University of Massachusetts Medical School, 1997-2002
Scholar of the Leukemia and Lymphoma Society, 1999-2004
Associate Professor, University of Massachusetts Medical School, 2002 - Present
Chromatin Structure and Regulation of Gene Expression, Cell Cycle, Cell Differentiation, and Oncogenesis
The main focus of our research is to understand how factors that regulate the opening and closing of chromatin structure affect a diverse set of biological processes, including gene expression, cell cycle progression, initiation of cellular differentiation, tumorigenesis, and mouse development. Most of our work focuses on the mammalian SWI/SNF complexes, which are multi-subunit, ATP-dependent enzymes that alter chromatin structure. These evolutionarily conserved enzymes physically alter the structure of chromatin to regulate gene expression. Surprisingly, component subunits of these enzymes can interact with known tumor suppressors to regulate cell growth and also can act as tumor suppressors themselves. Some subunits are required for embryogenesis. Additionally, SWI/SNF proteins can be targeted by viral regulatory proteins upon infection of cells by diverse viruses such as HIV, HPV and EBV.
Our past research efforts have reported isolation of human SWI/SNF complexes and functional characterization of their ability to alter in vitro assembled chromatin templates and promote transcription factor interactions with the template. Work on the mechanism of SWI/SNF mediated chromatin remodeling is ongoing in the lab, with specific interest in how post-translational histone modifications affect chromatin remodeling. To address biological function of these enzymes, we created cell lines that inducibly express mutant forms of the enzymes and are utilizing them to examine the role of these enzymes in numerous gene activation and cellular differentiation events. In particular, we have observed that expression of the mutant SWI/SNF chromatin remodeling enzymes prevents muscle and adipose differentiation. Detailed examination of the temporal interplay between tissue specific regulatory factors and diverse chromatin remodeling enzymes is in progress (see figure). To date, we have identified disparate functions for SWI/SNF enzymes at different promoters, including facilitation of pol II pre-initiation complex function and facilitation of activator binding to the promoter.
In addition, we are continuing our efforts to assess the function of the SWI/SNF subunit termed Ini1. Ini1 is missing or mutated in a number of pediatric rhabdoid and other tumors, suggesting it acts as a tumor suppressor. In collaboration with Steve Jones’ lab, we previously showed that approximately 15% of mice heterozygous for Ini1 exhibit tumors, predominantly in the head and neck region, demonstrating that Ini1 does act as a tumor suppressor. Ini1 null embryos die around the time of implantation in the womb, indicating that Ini1 is essential for normal mouse development. However, analysis of SWI/SNF function in Ini1 deficient cells derived from patient tumors shows that multiple SWI/SNF functions are unaffected by the absence of Ini1. Further analyses of ini1 function and the regulation of Ini1 expression are in progress.
Temporal order of events during activation of the PPARgamma gene during adipogenesis
(see Salma et al, MCB 24:4641, 2004)
Manuel Hernandez, Ph.D.
Postdoctoral Fellow 12/09-present
Yu-Jie Hu, M.S.
Graduate Student UMMS 7/09 - present
Karen M. Imbalzano, M.S.
Research Technician (joint with JA Nickerson), 5/03-present
Scott E. LeBlanc, Ph.D.
Postdoctoral Fellow, 9/07 - present
Recipient:NIH Postdoctoral Fellowship 5/10 – 4/13
Brian T. Nasipak, Ph.D.
Postdoctoral Fellow, 12/07 - present
Research Technician (joint with JA Nickerson) 8/10 - present
Qiong (Joae) Wu, Ph.D.
Postdoctoral Fellow 12/09 - present
Ok Hyun Cho, Ph.D.
Postdoctoral Fellow 10/09-2/11
Current Position:Postdoctoral Fellow, Dept. of Pathology, UMass Medical School
Chandrashekara Mallappa, Ph.D.
Postdoctoral Fellow, 9/07 -8/10
CurrentPosition: Postdoctoral Fellow, DartmouthMedical School
Nathalie Cohet, Ph.D.
Postdoctoral Fellow (joint with JA Nickerson) 4/06-12/08
Current Position:Parenting in Lyon, France.
Caroline S. Dacwag, Ph.D.
Graduate Student, UMMS, 5/02 – 7/08
Recipient:Zelda Haidak Memorial Scholar Fellowship 7/04 – 6/05
Ph.D. Recipient:UMMS, 7/08
Current Position:Postdoctoral Fellow, Massachusetts General Hospital, Mentor:Kenneth Chien, M.D., Ph.D.
Concetta G.A.Marfella, Ph.D.
Graduate Student, UMMS, 1/02 – 4/07
Recipient:Zelda Haidak Memorial Scholar Fellowship 7/05 – 6/06
Recipient:Zelda Haidak Memorial Scholar Fellowship 7/06 – 6/07
Ph.D. Recipient: UMMS 4/07
SubsequentPosition:Postdoctoral Fellow, Boston Children's Hospital, Mentor: Laurie Jackson-Grusby, Ph.D.
Current Position:Scientific Writer, Vertex Pharmaceuticals, Cambridge, MA
Yasuyuki Ohkawa, Ph.D.
Postdoctoral Fellow, 6/03-2/07
Subsequent Position:Assistant Professor (tenure-track), Kyushu University Medical School
Current Position: Associate Professor (tenure-track), Kyushu University Medical School
Hengyi Xiao, Ph.D.
Instructor, 2/02 - 8/06
Current Position:Assistant Professor, Department of Medicine, West China Center of Medical Sciences, Sichuan University
Nunciada Salma, Ph.D.
Graduate Student, UMMS, 9/00 - 3/06
Recipient:Zelda Haidak Memorial Scholar Fellowship 7/03 – 6/04
Ph.D. recipient: UMass Medical School, 3/06
Current Position:Postdoctoral Fellow, Massachusetts General Hospital, Mentor: David E. Fisher, M.D., Ph.D.
Kanaklata Roy, Ph.D.
Postdoctoral Fellow, 7/00 - 4/03
Subsequent Position:Postdoctoral Fellow, Brudnick Neuropsych. Inst.
Current Position: Registered Pharmacist and Instructor, Becker College, Worcester, MA
Ivana L. de la Serna, Ph.D.
Postdoctoral Fellow, 8/98 – 12/03
Research Assistant Professor, 1/04 – 8/05
Recipient:NIH Postdoctoral Fellowship 8/00-7/02
Recipient:Medical Foundation Fellowship 8/02-12/03
Recipient:American Heart Association Scientist Development Grant 1/04 – 12/07
Recipient:Transition to Independence Position (TIP) of the NIEHS (K22 Award) 3 year award made 3/04. Activated 9/05 upon start of independent position.
Current Position:Assistant Professor (tenure-track), Dept. Biochemistry and Cancer Biology, University of Toledo Health Sciences Center (formerly Medical University of Ohio)
David A. Hill, Ph.D.
Postdoctoral Fellow,7/98 – 12/04
Instructor, 1/05 – 6/06
Recipient:ACS Postdoctoral Fellowship 7/00-6/03
Recipient: American Heart Association Scientist Development Grant 6/06 (declined)
Current Position: Scientist, Athena Diagnostics, Inc., Worcester, MA
Cynthia J. Guidi, Ph.D.
Graduate Student, UMMS, 1/98 - 2/03
Ph.D. recipient:UMass Medical School, 2/03
Subsequent Position:Postdoctoral Fellow, U. Virginia Health Science Center,
Mentor: Mitchell Smith, Ph.D
Recipient:American Cancer Society Postdoctoral Fellowship 1/04-12/06
Current Position:Scientist II, ImunoGen, Inc., Waltham, MA
Kimberlee S. Mix, Ph.D.
Undergraduate, Worcester Polytechnic Institute, 6/97 - 4/98
Winner:WPI Provost’s Award - Most Outstanding Senior Research Project, 1998
Ph.D. recipient: Dartmouth College 9/03
Current Position: Assistant Professor (tenure track), Dept. Biological Sciences, Loyola University New Orleans
Project #1 The initiation of new programs of gene expression in differentiating cells requires chromatin remodeling enzymes in addition to tissue specific transcription factors. Characterization of the temporal events leading to gene activation during myogenesis and adipogenesis is ongoing using cell line models for differentiation. In vitro work with purified components is also ongoing to address mechanism of action. Multiple projects involving the role of chromatin remodeling enzymes during tissue specific gene expression are available.
Project #2 Loss of the Ini1 subunit of SWI/SNF enzymes in children causes malignant rhabdoid tumors. In mice, targeted elimination of Ini1 results in early embryonic lethality and mice heterozygous for Ini1 are susceptible to tumor formation. Attempts to understand the function of the Ini1 protein in gene expression, chromatin remodeling, cell cycle regulation, development, and oncogenesis are in progress using molecular biology, biochemistry, and mouse modeling.
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