
Adriano Marchese, PhD
Professor
Locations
- Biochemistry
TBRC C3850
Contact Information
Education
MSc, University of Toronto, 1994
BS, University of Toronto, 1991
Biography
Adriano Marchese received his Bachelor of Science Degree in Pharmacology in 1991 from the University of Toronto. He continued his graduate studies at the University of Toronto where he earned his MSc (1994) and PhD (1998) in Pharmacology. He then went to Thomas Jefferson University for his postdoctoral training. In 2004 he joined the faculty of the Department of Pharmacology at Loyola University Chicago. In 2016 he decided to move his lab to the Medical College of Wisconsin where he joined the faculty of the Biochemistry Department. Dr. Marchese has had a long-standing interest in understanding the molecular mechanisms governing G protein-coupled receptor signaling.
Research Interests
Research in the Marchese lab is directed towards understanding the molecular mechanisms governing G protein-coupled receptor (GPCR) signaling. GPCRs are cell surface receptors expressed throughout the body, mediating a wide variety of physiological processes such as smell, taste, vision, neurotransmission, cardiovascular control, chemotaxis, pain tolerance, immunity and much more. GPCRs are also targets, either directly or indirectly, of a large fraction of medicines prescribed worldwide to treat many diseases. Our goal is to elucidate the mechanisms governing GPCR signaling. We believe this will lead to a better understanding of how GPCR signaling contributes to disease, which may also help to identify new targets that could be used to develop new medicines with less side effects.
Our work is focused primarily on the chemokine receptor CXCR4, a prototypical GPCR implicated in several diseases. Of particular interest to us is the role that CXCR4 signaling plays in cancer progression. CXCR4 is over-expressed on the surface of many types of cancer cells and its expression correlates with poor prognosis. This is mainly because CXCR4 signaling contributes to metastatic disease, the cause of most cancer related deaths. CXCR4 expressing cancer cells tend to disseminate to and colonize anatomical sites where the cognate ligand for CXCR4, called CXCL12, is located. This includes the liver, bone marrow, lungs and lymph nodes among other tissues. Despite the importance of CXCR4 signaling in cancer the mechanisms remain poorly understood.
Current research efforts in the Marchese lab is in two areas. In one area we are focused on elucidating the molecular mechanisms regulating CXCR4 expression in cells. In particular, we are studying how CXCR4 levels are regulated by membrane trafficking within the endocytic pathway. Upon binding to CXCL12 at the cell surface CXCR4 rapidly internalizes and traffics along the endocytic pathway to lysosomes, a terminal degradative compartment. Modification of C-terminal tail lysine residues with ubiquitin by the E3 ubiquitin ligase AIP4 serves as a sorting signal for CXCR4 to enter the lysosomal degradative pathway. Consequently, this leads to a loss in the cellular complement of CXCR4 and long-term attenuation of signaling. Our goal is to understand the mechanisms governing CXCR4 ubiquitination and its sorting into the degradative pathway.
In another area of research, we are studying how CXCR4 signaling contributes to cell migration. CXCR4 expressing cancer cells move up a gradient of CXCL12, its cognate ligand, via a process known as directed cell migration or chemotaxis. This process contributes to tissue colonization and tumor cell metastasis. Our goal is to elucidate the signaling pathways that are responsible for CXCR4-promoted cell migration.
We use cell-free assays, cell culture models and primary cells in our research. We employ state-of-the-art genetic, pharmacological and biochemical approaches. We also use live-cell microscopy imaging to examine CXCR4 trafficking at the subcellular level along the endocytic pathway as well as to monitor cell migration along chemokine gradients using specialized microfluidic devices.
Publications
-
A non-GPCR-binding partner interacts with a novel surface on β-arrestin1 to mediate GPCR signaling.
(Zhuo Y, Gurevich VV, Vishnivetskiy SA, Klug CS, Marchese A.) J Biol Chem. 2020 10 09;295(41):14111-14124 PMID: 32753481 PMCID: PMC7549033 SCOPUS ID: 2-s2.0-85092803357 08/06/2020
-
The chemokine X-factor: Structure-function analysis of the CXC motif at CXCR4 and ACKR3.
(Wedemeyer MJ, Mahn SA, Getschman AE, Crawford KS, Peterson FC, Marchese A, McCorvy JD, Volkman BF.) J Biol Chem. 2020 10 02;295(40):13927-13939 PMID: 32788219 PMCID: PMC7535910 SCOPUS ID: 2-s2.0-85092681956 08/14/2020
-
(D'Agostino G, Artinger M, Locati M, Perez L, Legler DF, Bianchi ME, Rüegg C, Thelen M, Marchese A, Rocchi MBL, Cecchinato V, Uguccioni M.) Front Immunol. 2020;11:550824 PMID: 33072091 PMCID: PMC7533569 SCOPUS ID: 2-s2.0-85091956339 10/20/2020
-
Heterologous regulation of CXCR4 lysosomal trafficking.
(Caballero A, Mahn SA, Ali MS, Rogers MR, Marchese A.) J Biol Chem. 2019 05 17;294(20):8023-8036 PMID: 30936203 PMCID: PMC6527173 SCOPUS ID: 2-s2.0-85066114226 04/03/2019
-
Mitochondria-targeted drugs stimulate mitophagy and abrogate colon cancer cell proliferation.
(Boyle KA, Van Wickle J, Hill RB, Marchese A, Kalyanaraman B, Dwinell MB.) J Biol Chem. 2018 09 21;293(38):14891-14904 PMID: 30087121 PMCID: PMC6153299 SCOPUS ID: 2-s2.0-85054023214 08/09/2018
-
(English EJ, Mahn SA, Marchese A.) J Biol Chem. 2018 07 20;293(29):11470-11480 PMID: 29899118 PMCID: PMC6065176 SCOPUS ID: 2-s2.0-85050381858 06/15/2018
-
Detecting Cell Surface Expression of the G Protein-Coupled Receptor CXCR4.
(Nevins AM, Marchese A.) Methods Mol Biol. 2018;1722:151-164 PMID: 29264804 PMCID: PMC6345166 SCOPUS ID: 2-s2.0-85038862440 12/22/2017
-
(Alekhina O, Marchese A.) J Biol Chem. 2016 Dec 09;291(50):26083-26097 PMID: 27789711 PMCID: PMC5207078 SCOPUS ID: 2-s2.0-85002567012 10/30/2016
-
Monitoring Chemokine Receptor Trafficking by Confocal Immunofluorescence Microscopy.
(Marchese A.) Methods Enzymol. 2016;570:281-92 PMID: 26921951 PMCID: PMC5201001 SCOPUS ID: 2-s2.0-84959135724 02/29/2016
-
(Verma R, Marchese A.) J Biol Chem. 2015 Mar 13;290(11):6810-24 PMID: 25605718 PMCID: PMC4358107 SCOPUS ID: 2-s2.0-84924943410 01/22/2015
-
Regulation of GPCR Trafficking by Ubiquitin.
(Kennedy JE, Marchese A.) Prog Mol Biol Transl Sci. 2015;132:15-38 PMID: 26055053 PMCID: PMC4699176 SCOPUS ID: 2-s2.0-84942193272 06/10/2015
-
The ubiquitin ligase deltex-3l regulates endosomal sorting of the G protein-coupled receptor CXCR4.
(Holleman J, Marchese A.) Mol Biol Cell. 2014 Jun 15;25(12):1892-904 PMID: 24790097 PMCID: PMC4055268 SCOPUS ID: 2-s2.0-84902668477 05/03/2014