Molecular Biology of viruses. Coordinator: Brandimarti

From the perspective that viruses are the "nature's molecular biology lab", I'm interested to investigate virus-host interactions, aimed to uncover the molecular details and eventually exploit and repurpose dissected viral functions.

Research interests of the lab mainly focus on investigating viral functions to both understand the molecular basis of virus-host interactions for therapeutical intervention, and to explore potential repurposing of individual viral activities.

Mechanisms leading to neurodegeneration in HAND (HIV-Associated Neurocognitive Disorders) are the main focus of the lab. Though HIV (Human Immunodeficiency Virus) does not infect neurons, it creates a toxic environment for neuronal cells and alters their survival and function. These alterations are investigated to uncover the molecular details resulting in neurocognitive impairments.

A partially independent research interest focuses on the effect of viral proteins on cell cycle machinery. Upon viral infection, enzymes devoted to control cell cycle may be perturbed and change their specificity toward different substrates, with a different final outcome. This is particularly true in post-mitotic cells like neurons, where cell cycle molecules cannot play their established, canonical role.

Research themes

Effects of HIV-1 neurotoxins on lipid rafts-associated proteins

These studies aim to exploit the specific properties of US9 (a Herpes Simplex Virus transport protein), to study protein transport/accumulation in experimental models of HIV neurotoxicity. US9 will be used as a probe to monitor alterations of cellular proteins trafficking/distribution in neurons, and as a driver to target enzymatic activities to specific subcellular compartments, to untangle the relationship between viral neurotoxicity and APP processing.

Role of cks1 (cyclin dependent kinase subunit 1) in controlling cell cycle and activities of CDKs.

cks1 is a component of the CDK (cyclin dependent kinase) complex that drives and controls cell cycle. Its essential role in mitotic cells has been demonstrated in all eukaryotic organisms, from yeast to mammals. This project aims to investigate a possible alternative effect of cks1 in post-mitotic cells.

Lab members

Olimpia Meucci, Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia PA, USA (collaboration).

Main publications

Pedrazzi M, Nash B, Meucci O, Brandimarti R. Molecular Features Contributing to Virus-Independent Intracellular Localization and Dynamic Behavior of the Herpesvirus Transport Protein US9. PloS One. 2014;9(8):e104634. DOI:10.1371/journal.pone.0104634

Khan MZ, Brandimarti R, Shimizu S, Nicolai J, Crowe E, Meucci O.The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein. Cell Death Differ. 2008. 15(10):1663-72. DOI:10.1038/cdd.2008.95

LaVail JH, Tauscher AN, Sucher A, Harrabi O, Brandimarti R.Viral regulation of the long distance axonal transport of herpes simplex virus nucleocapsid. Neuroscience. 2007; 146(3):974-85. DOI:10.1016/j.neuroscience.2007.02.010

Khan MZ, Shimizu S, Patel JP, Nelson A, Le MT, Mullen-Przeworski A, Brandimarti R, Fatatis A, Meucci O. Regulation of neuronal P53 activity by CXCR 4.Mol Cell Neurosci. 2005;30(1):58-66. DOI:10.1016/j.mcn.2005.05.007

KHAN, M.Z., BRANDIMARTI, R., MUSSER, B.J., RESUE, D.M., FATATIS, A., and O. MEUCCI. The chemokine receptor CXCR4 regulates cell cycle proteins in neurons. J Neurovirol. Jun;9(3):300-14. 2003. DOI:10.1080/13550280390201010