
Siavash Kurdistani, M.D.
Bio
Siavash Kurdistani, M.D., studies histones – proteins that act as spools around which DNA is wound in the cell nucleus. He seeks to determine how histones and their biochemical changes, called modifications, regulate cellular metabolism, the process by which nutrients are converted to energy. Through this work, he aims to discover how histones contribute to the development and progression of cancer and other diseases in order to improve diagnosis, treatment and prevention strategies.
Historically, research on histone modifications, including past work from Kurdistani's lab, has focused on how they affect DNA-related processes such as switching genes on and off. Kurdistani now examines histone modifications’ broader functions, including how they affect cellular metabolism and physiology (the activities that take place inside of a cell to keep it alive). Kurdistani has found that histone modifications could directly affect cellular physiology, which could in turn cause changes in gene expression. For example, he has demonstrated that histone modifications can regulate cellular acidity, also known as pH, and that changes in pH levels can affect which genes are turned on or off.
Abnormalities in modifications of histones and other proteins that interact with histones are common in human diseases, especially cancer. Therefore, a better understanding of how histone modifications affect cells could enhance the understanding of how these diseases develop and progress, as well as reveal new treatment strategies. Kurdistani became interested in stem cell research because of the biological similarities between cancer cells and embryonic stem cells, specifically their ability to self-renew. He compares histone modifications of cancer cells and embryonic stem cells in order to understand cancer development and progression at a molecular level. He and his collaborators have discovered that measuring histone modifications can predict prognosis or response to treatment in certain groups of patients with cancers of the prostate, kidney, lungs, breasts and pancreas.
Kurdistani discovered a previously unsuspected role for histones in regulation of copper biology. Copper is a metal that is essential for numerous biological processes such as respiration, anti-oxidant defense, and metabolism of nutrients. These biological processes are important for all cells, especially those that divide rapidly such as embryonic stem cells. Kurdistani found that histones generate biousable copper for cellular processes that depend on this metal. This newly discovered function will open a novel field of inquiry on the biology of histones.
Kurdistani earned a medical degree from Harvard Medical School and completed post-doctoral training at UCLA.
Publications
- Transient nuclear deformation primes epigenetic state and promotes cell reprogrammingPublished in Nature Materials on Thursday, August 4, 2022
- Promoter-Enhancer Communication Occurs Primarily within Insulated NeighborhoodsPublished in Molecular Cell on Thursday, January 17, 2019
- Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineagePublished in Science on Thursday, October 4, 2018
- Glucose inhibits cardiac muscle maturation through nucleotide biosynthesisPublished in eLife on Tuesday, December 12, 2017
- MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4Published in Cell Reports on Wednesday, February 10, 2016
- Chromatin: a capacitor of acetate for integrated regulation of gene expression and cell physiologyPublished in Current Opinion in Genetics & Development on Thursday, July 10, 2014
- Evolution of histone 2A for chromatin compaction in eukaryotesPublished in eLife on Tuesday, June 17, 2014
- Adenovirus E4ORF1-Induced MYC Activation Promotes Host Cell Anabolic Glucose Metabolism and Virus ReplicationPublished in Cell Metabolism on Tuesday, April 1, 2014
- A unique epigenetic signature is associated with active DNA replication loci in human embryonic stem cellsPublished in Epigenetics on Tuesday, October 29, 2013
- Histone acetylation regulates intracellular pHPublished in Molecular Cell on Thursday, January 24, 2013
- Dynamic Distribution of Linker Histone H1.5 in Cellular DifferentiationPublished in PLOS Genetics on Thursday, August 30, 2012
- Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and EndocardiumPublished in Cell on Thursday, August 2, 2012
- Epigenetic reprogramming by adenovirus e1aPublished in Science on Friday, August 22, 2008
- Global histone modification patterns predict risk of prostate cancer recurrencePublished in Nature on Thursday, June 30, 2005
Honors & Affiliations
Honors
- Kavli Fellow, National Academy of Sciences, 2011
Affiliations
- Elected member, American Society for Clinical Investigation, 2019
- Gene Regulation Program Area, UCLA Jonsson Comprehensive Cancer Center
- Scientific advisory board, Neuromuscular Disease Foundation
Funding
Kurdistani’s work is supported by the National Institutes of Health and the W.M. Keck Foundation.