How the genome is used to make the appropriate combination of proteins in each cell is governed by epigenetics. I believe that the mysteries and wonders of epigenetics—especially as they relate to liver and heart tissue—can be solved with state-of-the-art molecular biology tools like those available here at Sanford-Burnham.
Dr. Khorasanizadeh's laboratory focuses on investigating epigenetic mechanisms, the emerging study of changes in gene expression.
Dr. Khorasanizadeh obtained her Ph.D. in Chemistry from the University of Pennsylvania in 1995.
View All Publications
Corecognition of DNA and a methylated histone tail by the MSL3 chromodomain.
Kim D, Blus BJ, Chandra V, Huang P, Rastinejad F, Khorasanizadeh S
Nat Struct Mol Biol. 2010 Aug;17(8):1027-9
Specificity of the chromodomain Y chromosome family of chromodomains for lysine-methylated ARK(S/T) motifs.
Fischle W, Franz H, Jacobs SA, Allis CD, Khorasanizadeh S
J Biol Chem. 2008 Jul 11;283(28):19626-35
Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation.
Rosasco-Nitcher SE, Lan W, Khorasanizadeh S, Stukenberg PT
Science. 2008 Jan 25;319(5862):469-72
Recognition of trimethyllysine by a chromodomain is not driven by the hydrophobic effect.
Hughes RM, Wiggins KR, Khorasanizadeh S, Waters ML
Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11184-8
Molecular implications of evolutionary differences in CHD double chromodomains.
Flanagan JF, Blus BJ, Kim D, Clines KL, Rastinejad F, Khorasanizadeh S
J Mol Biol. 2007 Jun 1;369(2):334-42
Double chromodomains cooperate to recognize the methylated histone H3 tail.
Flanagan JF, Mi LZ, Chruszcz M, Cymborowski M, Clines KL, Kim Y, Minor W, Rastinejad F, Khorasanizadeh S
Nature. 2005 Dec 22;438(7071):1181-5
Assays for the determination of structure and dynamics of the interaction of the chromodomain with histone peptides.
Jacobs SA, Fischle W, Khorasanizadeh S
Methods Enzymol. 2004;376:131-48
The nucleosome: from genomic organization to genomic regulation.
Cell. 2004 Jan 23;116(2):259-72
Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains.
Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S
Genes Dev. 2003 Aug 1;17(15):1870-81
The active site of the SET domain is constructed on a knot.
Jacobs SA, Harp JM, Devarakonda S, Kim Y, Rastinejad F, Khorasanizadeh S
Nat Struct Biol. 2002 Nov;9(11):833-8
Sepideh Khorasanizadeh's Research Focus
Heart Disease, Infectious Diseases, Cancer, Diabetes - General
Watch Dr. Khorasanizadeh describe her research
A significant body of research suggests that therapeutic targeting of specific gene expression pathways may be key to personalized medicine. Since 1999, the Khorasanizadeh laboratory has devoted its efforts to investigating epigenetic mechanisms, the emerging study of changes in gene expression caused by mechanisms other than changes in the DNA sequence. By applying powerful tools of biochemistry and biophysics they have discovered gene-switching mechanisms that control transcription phenomena.
Sepideh Khorasanizadeh's Research Report
Chromatin complexes (consisting of histone and nonhistone proteins, RNA molecules and DNA within the nucleus) keep a reign on transcription factor binding to maintain appropriate transcription patterns in eukaryotes. Our laboratory has been studying the conserved protein structures that specifically mark and recognize histone and nucleic acid components in chromatin of yeast, flies, plants and mammals. We have characterized lysine methyltransferases and methyllysine recognition factors to understand the putative function of histone lysine methylation in maintenance and memory of active and repressed transcription phenomena. Complementary biophysical and chemical approaches have revealed structural and thermodynamic principles of chromatin regulations, uncovering an unexpected diversity of signaling and regulation among eukaryotes. Chromatin/epigenetic regulations in humans involve complex modulations of transcription factor binding and signaling responses not readily amenable to therapeutic intervention. We plan to delineate specific mechanisms of transcription control in cardiovascular disease and diabetes. We are also interested in identifying drug or tool compounds that target the active sites in chromatin/transcription factors.
Parallel efforts are devoted to delineating the basis for maintenance and memory of active and repressed transcription phenomena in eukaryotic pathogens that infect humans. By understanding the basis for chromatin regulation in pathogens we hope to identify diagnostic tools and therapeutic targets. This list of protozoan organisms often affect the human intestine and cause a variety of diseases. We chose to focus on
Entamoeba histolytica, the cause of amoebiasis, because its genome is annotated (encodes about 8000 genes), gene transcription levels have been measured in both the dormant cyst and the active trophozoite stages, and most importantly, there is an established mouse model for investigating the disease. We noticed a major deviation in the histone language of this organism and have focused our investigations on the activity of lysine methyltransferases and methyllysine recognition factors.
About Sepideh Khorasanizadeh
Sepideh Khorasanizadeh, Ph.D., joined Sanford-Burnham in 2010. Previously, she was on the faculty of the department of Biochemistry and Molecular Genetics at the University of Virginia from 1999 to 2010, studying biophysical properties of chromatin, epigenetic and transcription factors. Prior to becoming a faculty member in Virginia, she was a Leukemia Society special fellow at University of Maryland Baltimore County in Michael Summers’ group focusing on NMR structure determination of retroviral capsid proteins.
Sepideh obtained her Ph.D. in Chemistry from the University of Pennsylvania in 1995, completing her thesis at the Fox Chase Cancer Center, where in Dr. Heinrich Roder’s group she studied the folding mechanism of ubiquitin by spectroscopy. Sepideh was born in Iran, and graduated from high school in Tehran in 1985. Serendipitously, she entered University of Massachusetts where college level chemistry courses ignited a lifetime passion in laboratory research, whereas summer positions at Nestle research lab instilled interest in food sources and cooking.
Post-doc, University of Maryland, Howard Hughes Medical Institute, 1999
Ph.D., University of Pennsylvania, Chemistry Department, 1995
B.S. with Honors, University of Massachusetts, Chemistry Department, 1990
Visiting Associate Professor, University of Virginia
Honors and Recognition
Established Investigator of the American Heart Association, 2007–2011
Special Fellow of the Leukemia and Lymphoma Society, 1999–2001
Cancer Research Institute Postdoctoral Fellowship, 1998
HHMI postdoctoral associate, University of Maryland, 1995–1998
The American Chemical Society Outstanding Senior Award, 1990