Vojo Deretic, is distinguished professor and chair of the Department of Molecular Genetics and Microbiology at the University of New Mexico School of Medicine. Deretic was the founding director of the Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence. The AIM center promotes autophagy research nationally and internationally.
Education
Vojo Peter Deretic received his undergraduate, graduate and postdoctoral education in Belgrade, Paris, and Chicago. He was a faculty member at the University of Texas, University of Michigan, and joined University of New Mexico Health Sciences Center in 2001.
Career and research
Vojo Deretic's main contributions to science come from studies by his team on the role of autophagy in infection and immunity. Autophagy is a cytoplasmic pathway with quality control and metabolic roles. Autophagic removal of damaged or surplus organelles, has been implicated in cancer, neurodegeneration such as Alzheimer's disease, Huntington's disease and Parkinson's disease, diabetes, development, and aging. Deretic's group is one of those that made the discovery that autophagic degradation is a major effector of innate and possibly adaptive immunity mechanisms for direct elimination of intracellular microbes (such as Mycobacterium tuberculosis). This has placed immunity and infection on the repertoire of autophagy's sphere of influence.
Studies in the Deretic laboratory have contributed to our understanding of the basic mechanisms of autophagy in mammalian and human cells applicable to generic, i.e. metabolic and quality control autophagy, as well as to autophagy processes specializing in immune functions. The work by Deretic and colleagues has shown how autophagosomes form in mammalian cells, identifying HyPAS (hybrid pre-autophagosomal structure) prophagophores as direct precursors to autophagosomes in mammalian cells. The HyPAS prophagophores are formed through a membrane fusion between endosomes endowed with the E3 ligase ATG16L1 and the cis-Golgi derived FIP200 vesicles and cisternae. By subsequent atg8ylation, a nascent prophagophore converts into an LC3-positive phagophore. LC3B is one of the six major mammalian ATG8 proteins, which modify membranes in a process referred to as atg8ylation, analogous to the process of protein modification via ubiquitylation. Autophagosomal phagophores expand through lipid transfer processes dependent on ATG9A and ATG2A/B whereas mATG8s play multiple roles, one of which is to serve as adaptors for autophagic receptors thus sequestering cargo into the autophagosomal lumen. The latest findings form Dr. Deretic's laboratory show that atg8ylation and mATG8s play a role in recruiting ESCRT machinery to seal open phagophores, thus generating double membrane autophagosomes, and to maintain autophagosomal membranes in a sealed and impermeable, i.e. nonporous state so that digestion of the captured material can take place.
The tight relationship between autophagy as a quality control and metabolic process on the one hand, and as innate immunity process on the other hand, probably harks back to the bacterial endosymbiotic origins of mitochondria. From bacteria to viruses, autophagy and autophagy-related processes, often referred to as non-canonical autophagy, recently categorized as different manifestations of membrane atg8ylation, play roles in controlling microbes or are targeted by pathogens. For example, as shown in a study from the Deretic laboratory, SARS-CoV-2 inhibits the earliest stage of autophagosome formation in human cells known as the prophagophore or HyPAS.