Sina Ghaemmaghami

Assistant Professor

Contact Information:

University of Rochester
Department of Biology

River Campus Box 270211
Rochester, New York 14627-0211

Hutchison 326A (office)
Hutchison 336 (lab)

(585) 275-4829 (office)
(585) 276-1237 (lab)

Research Overview

Our laboratory has a general interest in understanding the mechanisms of protein expression, folding and degradation. We investigate how cells maintain a homeostatic balance between these processes, and how this homeostasis is effected by disease and aging. The projects in the lab draw on a number of disciplines including cell biology, biochemistry, systems biology and computational biology. Two current projects are described below:

The mechanism of prion propagation and pathogenesis
Most proteins populate a single, ordered three-dimensional structure in solution. However, a subset of proteins, termed prions, have the capacity to fold into alternative self-replicating conformations, enabling a single polypeptide sequence to be associated with multiple phenotypes. The ability of prions to fold into diverse meta-stable, self-seeding conformations facilitates two protein-based functionalities that were previously thought to require the involvement of nucleic acid-based genetic elements: infectivity and heritability. Although historically associated with a group of neurodegenerative disorders in mammals, prions have now been discovered in a number of organisms and have been implicated in the regulation of non-pathogenic biological activities including translation, transcription, mating compatibility and memory. Current projects in the lab are seeking to understand the cellular mechanisms of prion propagation and pathogenesis - and to identify effective therapeutics against prion diseases.

Global analysis of protein expression and turnover
A central focus of the lab is the development of novel methodologies for system-wide analysis of protein homeostasis. Specifically, we are developing proteomic techniques that can measure the kinetics of protein formation and degradation on proteome-wide scales. We are using these approaches to assess the impact of protein aggregate accumulation on proteome dynamics in models of aging and neurodegenerative diseases. It is hoped that these proteomic screens will identify novel molecular pathways involved in age-dependant neurodegenerative diseases.


Figure 1. Protocol, model, and analysis of global turnover rates by isotopic labeling and mass spectrometry. (A) 15N-labeled algae are used to supply protein in the mouse diet. At designated time-points following the initiation of 15N labeling, tissues are collected, fractionated, and analyzed by mass spectrometry (MS). (B) Changes in the molecular weights of labeled peptides over time (shown for the Coffilin-1 protein) are dependent on the turnover rates of the corresponding proteins. Thus, turnover rates can be measured on proteome-wide scales by quantitative modeling and bioinformatic analysis of dynamic MS data.


  • Guan S, Price JC, Prusiner SB, Ghaemmaghami S, Burlingame AL. A data processing pipeline for mammalian proteome dynamics studies using stable isotope metabolic labeling. Mol Cell Proteomics. 2011 Sep 21. [Epub ahead of print] PubMed PMID: 21937731.
  • Poncet-Montange G, St Martin SJ, Bogatova OV, Prusiner SB, Shoichet BK, Ghaemmaghami S. A survey of antiprion compounds reveals the prevalence of non-PrP molecular targets. J Biol Chem. 2011 Aug 5;286(31):27718-28. Epub 2011 May 24. PubMed PMID: 21610081; PubMed Central PMCID: PMC3149362.
  • Ghaemmaghami S, Watts JC, Nguyen HO, Hayashi S, Dearmond SJ, Prusiner SB. Conformational Transformation and Selection of Synthetic Prion Strains. J Mol Biol. 2011 Aug 4. [Epub ahead of print] PubMed PMID: 21839745.
  • Price JC, Guan S, Burlingame A, Prusiner SB, Ghaemmaghami S. Analysis of proteome dynamics in the mouse brain. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14508-13. PubMed PMID: 20699386; PubMed Central PMCID: PMC2922600.
  • Ghaemmaghami S, Ullman J, Ahn M, St Martin S, Prusiner SB. Chemical induction of misfolded prion protein conformers in cell culture. J Biol Chem. 2010 Apr 2;285(14):10415-23. Epub 2009 Dec 2. PubMed PMID: 19955177; PubMed Central PMCID: PMC2856248.
  • Ghaemmaghami S, May BC, Renslo AR, Prusiner SB. Discovery of 2-aminothiazoles as potent antiprion compounds. J Virol. 2010 Apr;84(7):3408-12. Epub 2009 Dec 23. PubMed PMID: 20032192; PubMed Central PMCID: PMC2838138.
  • Ghaemmaghami S, Ahn M, Lessard P, Giles K, Legname G, DeArmond SJ, Prusiner SB. Continuous quinacrine treatment results in the formation of drug-resistant prions. PLoS Pathog. 2009 Nov;5(11):e1000673. Epub 2009 Nov 26. PubMed PMID:19956709; PubMed Central PMCID: PMC2777304.
  • Ingolia NT, Ghaemmaghami S, Newman JR, Weissman JS. Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science. 2009 Apr 10;324(5924):218-23. Epub 2009 Feb 12. PubMed PMID: 19213877; PubMed Central PMCID: PMC2746483.
  • Ghaemmaghami S, Phuan PW, Perkins B, Ullman J, May BC, Cohen FE, Prusiner SB. Cell division modulates prion accumulation in cultured cells. Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):17971-6. Epub 2007 Nov 7. PubMed PMID: 17989223; PubMed Central PMCID: PMC2084281.
  • Newman JR, Ghaemmaghami S, Ihmels J, Breslow DK, Noble M, DeRisi JL, Weissman JS. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature. 2006 Jun 15;441(7095):840-6. Epub 2006 May 14. PubMed PMID: 16699522.
  • Howson R, Huh WK, Ghaemmaghami S, Falvo JV, Bower K, Belle A, Dephoure N, Wykoff DD, Weissman JS, O'Shea EK. Construction, verification and experimental use of two epitope-tagged collections of budding yeast strains. Comp Funct Genomics. 2005;6(1-2):2-16. PubMed PMID: 18629296; PubMed Central PMCID: PMC2448600.
  • Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS. Global analysis of protein expression in yeast. Nature. 2003 Oct 16;425(6959):737-41. PubMed PMID: 14562106.
  • Powell KD, Ghaemmaghami S, Wang MZ, Ma L, Oas TG, Fitzgerald MC. A general mass spectrometry-based assay for the quantitation of protein-ligand binding interactions in solution. J Am Chem Soc. 2002 Sep 4;124(35):10256-7. PubMed PMID: 12197709.
  • Ghaemmaghami S, Oas TG. Quantitative protein stability measurement in vivo. Nat Struct Biol. 2001 Oct;8(10):879-82. PubMed PMID: 11573094.
  • Ghaemmaghami S, Fitzgerald MC, Oas TG. A quantitative, high-throughput screen for protein stability. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8296-301. PubMed PMID: 10890887; PubMed Central PMCID: PMC26941.
  • Ghaemmaghami S, Word JM, Burton RE, Richardson JS, Oas TG. Folding kinetics of a fluorescent variant of monomeric lambda repressor. Biochemistry. 1998 Jun 23;37(25):9179-85. PubMed PMID: 9636065.