Oscar Alzate, Ph.D.

Alzate
alzate@email.unc.edu
website

Associate Professor

  • Physicist: University of Antioquia - Medellín, Colombia.
  • Mathematician: Pontifical Bolivariana University - Medellín, Colombia
  • M.Sc. (Biophysics): The Ohio State University - Columbus, OH. USA
  • Ph.D. (Mol. Biophysics): The Ohio State University - Columbus, OH. USA.
  • Post-doc. (Biochemistry/Proteomics): The Ohio State University - Columbus, OH. USA.
  • Diploma. (Neurophysics). International Centre for Theoretical Physics - Trieste, Italy.

Research Interests

The Alzate Laboratory for Neuroproteomics and Neurodegeneration at the University of North Carolina School of Medicinehas two major interests:

1. Understanding the "Dynamics" of specific proteomes (PROTEOME DYNAMICS), under the influence of environmental and genetic factors. In particular we seek to understand how a proteome changes under oxidative stress. Findings that we seek to apply to any biological system under "normal" and "disease" conditions.

  • A proteome, contrary to popular culture, is not the "complement" of a genome. The genome of a cell or organism is pretty much well-established from birth. However, the proteome is the "permanently-changing", set of ALL the proteins that define each cell and organ at any give time. Therefore, the proteome IS NOT defined by the genome. The Genome only determines the proteins that will be synthesized from this genetic code at the beginning. Once the proteins are synthesized, they will undergo significant changes that will make the proteome a product of environmental factors (such as temperature, pH, oxidative stress, ionic strength, etc), protein-protein interactions, protein-D/RNA interactions, and posttranslational modifications. Taking into consideration how many conditions act upon any cell or organism, it is clear that there is NOT a single proteome.
  • Our laboratory discovered that the mitochondrial Heat Shock protein 70 (aka MORTALIN, PBP74, GRP75, mtHsp70, p66sh, among other names) is differentially regulated in the brains of human APOE targeted replacement (hApoE-TR) mice. These mice were originally developed at the laboratory of Dr. Oliver Smithies at UNC, these mice express either of the human APOE isoforms of this protein (APOE2, APOE3, and APOE4) and are used as animal models to study the biological role played by ApoE. The finding that mortalin is differentially expressed in these mice became relevant for neurodegeneration research because APOE is the only human gene known to confere a risk of developing Alzheimer's disease (AD). Following this initial finding, we analyzed brain tissues from AD patients and found that mortalin is also differentially regulated in these brains as a function of both, the genotype (APOE3/3, and APOE4/4) and the disease state. We found that mortalin is expressed in the human brain as four isoforms that can be fractionated using Isoelectric focusing, which suggested that such isoforms may be differentially phosphorylated between disease and non-disease states; hypothesis that we have not demosntrated despite extensive analysis of mortalin isoforms using LC-MS/MS and MALDI-MS/MS spectrometry.
  • We have tried to implement several approaches to understand the biological role played by mortalin in neurodegeneration. As our initial approach, and based in an extensive literature existing on mortalin structure and function, we proposed that mortalin undergoes post-translational modifications as a cellular response to avoid deleterious effects from oxidative stress, therefore, mortalin would be a perfect target to understand the physiological effects of oxidative stress, and other mechanisms that alter the cell's homeostasis. We started by constructing clones intended at over expressing mortalin in mouse-derived astrocytes (APOE3/3 and APOE4/4), and vectors whose aim was to decrease mortalin expression by shRNA-targeted gene silencing.

2. We seek to develop techniques to isolate, identify and characterize proteomes and subproteomes.

Selected Publications

PubMed 1