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Jose L. Avalos

Contact Information

javalos@wi.mit.edu

Research

Development of renewable liquid transportation fuels is a key component of the international strategy to reduce CO2 emissions and slow the progression of global climate change. While ethanol is the most successful biofuel to date, its physicochemical properties and current methods of production make it an inadequate long-term solution to this problem. Therefore, microbial strains need to be developed that produce advanced biofuels that overcome ethanol’s limitations. The goal of my research, which is carried out in close collaboration with Gerald Fink from the Whitehead Institute, is to engineer natural and synthetic metabolic pathways to develop microbial strains that produce alternative fuels to ethanol. My interests include synthetic biology, metabolic engineering, enzymology, structural biology and protein engineering.

Education

PhD (2004) Johns Hopkins University School of Medicine. Baltimore, MD.

MSc (1998) Imperial College, University of London. London, UK.

BEng (1997) Universidad Iberoamericana, Mexico City, Mexico.

Publications

  1. Smith JS, Brachmann CB, Celic I, Kenna MA, Muhammad S, Starai VJ, Avalos JL, Escalante-Semerena JC, Grubmeyer C, Wolberger C, Boeke JD. “A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family”. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6658-63.
  2. Sauve, AA., Celic, I., Avalos, JL., Deng, H., Boeke, JD., and Schramm, VL.Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions”. Biochemistry 2001 Dec 25; 40(51): 15456-15463.
  3. Smith J.S., Avalos, JL., Celic, I., Muhammad, S., Wolberger, C., and Boeke, J.D. “Sir2 family of NAD(+)-dependent protein deacetylases”. Methods Enzymol, 2002; 353: 282-300.
  4. Avalos, JL., Celic, I., Muhammad, S., Cosgrove, MS, Boeke, JD., and Wolberger, C.Structure of a Sir2 Enzyme Bound to an Acetylated  p53 Peptide”. Mol. Cell. 2002; Sep;10(3): 523-535.
  5. Avalos, JL., Boeke, JD., and Wolberger, C. “Structural Basis for the Mechanism and Regulation of Sir2 Enzymes”. Mol. Cell. 2004; Mar;12(13): 639-648.
  6. Avalos, JL., Bever, MK., Wolberger, C. “Structure-Based Mechanism of Sirtuin Inhibition by Nicotinamide: Altering the NAD+ cosubstrate specificity of a Sir2 enzyme”. Mol Cell. 2005 Mar 18;17(6):855-68.
  7. Cosgrove, MS., Bever, K., Avalos, JL., Muhammad, S., Zhang, X., Wolberger, C. “The Structural Basis of Sirtuin Substrate Affinity”. Biochemistry. 2006 Jun 20;45(24):7511-21.
  8. Hoff, K., Avalos, JL., Sens, K. and Wolberger, C. “Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide”. Structure. 2006 Aug;14(8):1231-40.
  9. Tao X, Avalos JL, Chen J, MacKinnon R. “Crystal structure of the eukaryotic strong inward-rectifier K+ channel Kir2.2 at 3.1 A resolution”. Science. 2009 Dec 18;326(5960):1668-74.

Patents

  • Avalos JL. and Wolberger C. Title:Identifying a modulator of the Sir2 enzyme activity, contacting a Sir2 enzyme with a compound for modulation of the Sir2 enzyme activity, and detecting modulation of the Sir2 enzyme activity by the compound”. Patent Number(s): WO2006081329-A2; EP1844157-A2. A new structure-based strategy to design drugs with therapeutic potential for certain types of cancer, age-related ailments and other diseases. Filed Jan. 2006. Issued Sep. 2008.