Vojo Deretic, Ph.D.
Department Chairperson
Molecular Genetics and Microbiology
University of New Mexico HSC
915 Camino de Salud NE
Albuquerque, NM 87131
 
Office: BMSB 353
Tel: (505) 272-0291
Fax: (505) 272-6029
E-mail: vderetic@salud.unm.edu

Keywords: Autophagy, macrophage, respiratory epithelial cells, tuberculosis, HIV, cystic fibrosis, phagosome, endosome, trans-Golgi network, membrane trafficking, small GTPases, microbial pathogenesis, nanomedicine

Research Interests

I. Autophagy. Autophagy is as a fundamental biological process defined as a cytoplasmic homeostasis pathway whereby cytoplasm portions get sequestered by membrane for delivery to lysosomes. This leads to removal of damaged or surplus organelles and turnover of stable, long-lived macromolecules. Autophagy has been previously implicated in both health-promoting and disease-associated states in cancer, neurodegeneration, development, and aging. Literally, within last year, a simultaneous discovery has been made by independent groups, including ours, showing that autophagic degradation is a major effector of innate and possibly adaptive immunity mechanism for direct elimination of intracellular microbes and other aspects of immunity. Autophagy is an area of intense study in our group.

II. Tuberculosis. Phagolysosome biogenesis as a fundamental organelle trafficking process and a key aspect of pathogenesis in tuberculosis. Our interests are focusing on normal trafficking processes and how they are altered during pathogenesis of infectious disease with the emphasis on intracellular survival of Mycobacterium tuberculosis.

III. AIDS. HIV infect phagocytic cells early in the transmission process with macrophages play a major role as the source of persistent virus during late stages of AIDS when CD4+ T cells become depleted.  In macrophages, HIV utilizes a normal cellular membrane trafficking pathway routinely generating vesicles within late endosomal compartments referred to as multivesicular bodies (MVB) due to their appearance as sacs filled with internal vesicles. Substitute normal internal vesicles with HIV virions, and you get the picture of what the virus does. Thus, a good part of HIV life cycle rests upon fundamental membrane trafficking and protein sorting within the endosomal system. In collaboration with Dr. Antonito Panganiban, MGM, we are studying HIV trafficking events and investigating ways of inhibiting HIV in MVB organelles, as well as analyzing synergism between tuberculosis and HIV, as both pathogens converge upon the same trafficking pathway in the host cell.

IV. Cystic Fibrosis (CF) is the most common inheritable lethal disease among Caucasians. Using a ratiometric pH-sensitive GFP variant, We have found, that intracellular organelles are hyperacidified in CF lung epithelial cells.  These findings are the basis for clinical trials that are about to begin in collaboration with Dr. Elizabeth Perkett, Pediatrics, who is the CF Center director at UNM SOM. The expected outcome measures are reduced infection, inflammation, and pulmonary decline. This is an example of how cell biology studies can take in one step basic research findings to the bedside.

V. Nanomedicine. Our laboratory relies heavily on imaging, and uses routinely techniques of confocal microscopy, live 4D imaging of dynamic intracellular events, ratiometric imaging (pH and Ca2+), particle tracking, FRET, TIRF, flow cytometry, and will soon be equipped for high resolution confocal live microscopy. In these processes we are developing means of applying nanotechnology as an approach to interrogate intracellular trafficking processes and learn about the physical properties of intracellular pathogens that may play a role in affecting the host cells. We collaborate with Drs. Graham Timmins, school of Pharmacy and Dr. David Peabody, who leads the nanobioscience effort in our Department and broader within the HSC.

For information about post-doc positions in the Deretic lab, see Job Opportunities.

For Deretic Laboratory Supplementary Materials  

Selected Recent Publications (out of 112 PubMed listed publications)

Fratti, R. A., J. Chua, I. Vergne, and V. Deretic. 2003. Mycobacterium tuberculosis glycosylated phosphatidylinositol causes phagosome maturation arrest. Proc. Natl. Acad. Sci. USA USA. 100: 5437-5442.

Vergne, I., J. Chua, and V. Deretic. 2003. Tuberculosis Toxin Blocking Phagosome Maturation Inhibits a Novel Ca2+/Calmodulin-PI3K hVPS34 Cascade. J Exp Med 198:653-609. (Journal cover page).

Vergne, I., R.A. Fratti, P.J. Hill, J. Belisle and V. Deretic. 2004. Mycobacterium tuberculosis phagosome maturation arrest: mycobacetrial phosphatidylinositol analog PIM stimulates early endosomal fusion. Mol. Biol. Cell. 15:751-760.

Chua, J., I. Vergne, S. Master, and V. Deretic. 2004. A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest. Curr Opin Microbiol 7:71-7

Firoved, A. M., S. R. Wood, W. Ornatowski, V. Deretic, and G. S. Timmins. 2004. Microarray Analysis and Functional Characterization of the Nitrosative Stress Response in Nonmucoid and Mucoid Pseudomonas aeruginosa. J Bacteriol 186:4046-50.

Firoved, A. M., W. Ornatowski, and V. Deretic. 2004. Microarray analysis reveals induction of lipoprotein genes in mucoid Pseudomonas aeruginosa: implications for inflammation in cystic fibrosis. Infect Immun 72:5012-8

Timmins, G. S., S. Master, F. Rusnak, and V. Deretic. 2004. Requirements for nitric oxide generation from isoniazid activation in vitro and inhibition of mycobacterial respiration in vivo. J Bacteriol 186:5427-31.

Vergne, I., R. A. Fratti, P. J. Hill, J. Chua, J. Belisle, and V. Deretic. 2004. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol Biol Cell 15:751-60.

Chua, J., and V. Deretic. 2004. Mycobacterium tuberculosis reprograms waves of phosphatidylinositol 3-phosphate on phagosomal organelles. J Biol Chem 279:36982-92.

Deretic, V., I. Vergne, J. Chua, S. Master, S. B. Singh, J. A. Fazio, and G. Kyei. 2004. Endosomal membrane traffic: convergence point targeted by Mycobacterium tuberculosis and HIV. Cell Microbiol 6:999-1009

Vergne, I., J. Chua, S. B. Singh, and V. Deretic. 2004. Cell biology of mycobacterium tuberculosis phagosome. Annu Rev Cell Dev Biol 20:367-94.

Gutierrez, M. G., S. S. Master, S. B. Singh, G. A. Taylor, M. I. Colombo, and V. Deretic. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119:1-20.

Deretic, V. 2005. Autophagy in innate and adaptive immunity. Trends Immunol 26:523-8.

Deretic, V. 2005. Ay, there's the rab: organelle maturation by Rab conversion. Dev Cell 9:446-8.

Vergne, I., J. Chua, H. H. Lee, M. Lucas, J. Belisle, and V. Deretic. 2005. Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 102:4033-8.

Singh, S.B., A. Davis, G. A. Taylor, and V. Deretic. 2006. Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria. Science 3 August 2006: 11295771 DOI: 10.1126/science.1129577
Click on the link for free access to the reprint pdf.