Carolyn Machamer


Office: 410-955-1809

725 N. Wolfe Street
105 WBSB
Baltimore MD 21205

Dr. Machamer is an active member of BCMB, however she is no longer accepting students in her lab.

Cell Biology

We are interested in the structure and function of the Golgi complex, a ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids in the secretory pathway. The Golgi complex has an unusual structure, particularly in vertebrates, where stacks of cisternal membranes are clustered into a ribbon structure near the nucleus. One goal of our research is to understand the role of this structure in Golgi function. Towards this goal, we are studying the targeting and function of resident Golgi proteins. We are interested in the contribution of the lipid bilayer to targeting of transmembrane Golgi proteins, and in the function of a group of peripheral Golgi membrane proteins called golgins. Several golgins, including golgin-160, are substrates for caspase cleavage during programmed cell death (apoptosis). Our hypothesis is that specific stress signals are transduced at Golgi membranes, and that cleavage of golgin-160 may be critical for downstream signaling events. In non-apoptotic cells, golgin-160 is involved in trafficking of specific cargo molecules, including the beta-1-adrenergic receptor, and the insulin-regulated glucose transporter, GLUT4.     The other research interest in the lab is the assembly mechanism of coronaviruses, enveloped viruses that bud into Golgi compartments. Coronaviruses are vertebrate pathogens that usually cause mild respiratory or gastrointestinal disease. However, the emergence of severe acute respiratory syndrome (SARS), which is caused by a novel coronavirus, has sparked much interest in this group of viruses. We are addressing how coronaviruses target their envelope proteins to Golgi membranes, and how they interact with each other at the virus assembly site. We are also exploring how coronaviruses are exocytosed after they bud into the Golgi lumen. Our long-term goal is to understand the advantages of intracellular assembly for coronaviruses. A better understanding of intracellular assembly and the mechanism of exocytosis should lead to novel strategies for antiviral therapeutics. In addition, we are using coronavirus egress as a model for secretion of large cargo, since the size of the virions results in modification of Golgi structure to allow accommodation of these particles. We hope to learn how other large cargo is trafficked through the Golgi (e.g. chylomicrons in the intestine).

Gonzales, R.R. and Machamer, C.E. 2021. The SARS COV-1 3a protein disrupts Golgi complex morphology and cargo trafficking.

Westerbeck, J.W. and C.E. Machamer. 2019. The infectious bronchitis virus coronavirus envelope protein alters Golgi pH to protect spike protein and promote release of infectious virus. J. Virol.93(11):1-15. PMCID: PMC6532078

Gilbert, C.E., E. Sztul and C.E. Machamer. 2018. Commonly used trafficking blocks disrupt ARF1 activation and the localization and function of specific Golgi proteins. Molec. Biol. Cell, E17-11-0622. doi: 10.1091/mbc.E17-11-0622.

Sisk, J.M., M.B. Frieman and C.E. Machamer. 2018. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. J. Gen. Virol., Mar 20. doi: 10.1099/jgv.0.001047

Machamer, C.E. 2015. The Golgi complex in stress and death. Front. Neurosci. 9:421. PMCID: PMC4635215

Westerbeck, J.W. and C.E. Machamer. 2015. A coronavirus E protein is present in two distinct pools with different effects on assembly and the secretory pathway. J. Virol., 89:9313-9323. PMCID: PMC4542375

Gilbert, C.E., D.M. Zuckerman, P.L. Currier, and C.E. Machamer. 2014. Three basic residues of intracellular loop 3 of the beta-1 adrenergic receptor are required for golgin-160-dependent trafficking. Int. J. Mol. Sci.15:2929-45. PMCID: PMC3958891

Taylor M.S., Ruch T.R., Hsiao P.Y., Hwang Y., Zhang P, Dai P.L., Huang C.R., Berndsen C.E., Kim M.S., Pandey A., Wolberger C., Marmorstein R.,  Machamer C.E., Boeke J.D., and Cole P.A.. 2013. Architectural organization of the metabolic regulatory enzyme ghrelin-O-acyltransferease. J. Biol. Chem.288:32212-28. PMCID: PMC3820860.

Sbodio J.I., Paul B.D., Machamer C.E. and Snyder S.H.. 2013. Golgi protein ACBD3 mediates neurotoxicity associated with Huntington’s disease. Cell Reports 4:890-897.

Machamer C.E. 2013. Accommodation of large cargo within Golgi cisternae. Histochem. Cell Biol., 140:261-269.

Chandran S. and Machamer C.E.. 2012. Inactivation of ceramide transfer protein during proapoptotic stress by Golgi disassembly and caspase cleavage. Biochem. J., 442:391-402.

Ruch T.R. and Machamer C.E. 2012. The coronavirus E protein: assembly and beyond.  Viruses 4:363-382.

Ruch T.R. and Machamer C.E.. 2012. A single polar residue and distinct membrane topologies impact the function of the infectious bronchitis coronavirus E protein. PLoS Pathogens 8(5):e1002674.

Ruch T.R. and Machamer C.E 2011. The hydrophobic domain of the infectious bronchitis virus E protein alters the host secretory pathway and is important for release of infectious virus.  J. Virol. 85:675-685.

Zuckerman D.M., Hicks S.W., Charron G., Hang H.C., and Machamer C.E2011. Differential regulation of two palmitoylation sites in the cytoplasmic tail of the beta-1 adrendergic receptor. J. Biol. Chem. 286:19014-23

Cohen J.R., Lin L.D. and Machamer C.E.. 2011. Identification of a Golgi targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein. J. Virol. 85:5794-5803.

Chandran S. and Machamer C.E. 2010. Golgi organization and stress sensing. The Golgi apparatus: Structure, Functions and Mechanisms.  (Nova Science, Inc, Hauppauge NY).

Mcbride C.E. and Machamer C.E 2010. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein. Virology 405:139-148.

McBride C.E. and Machamer C.E2009. A single tyrosine in the SARS coronavirus membrane protein is important for interaction with the spike protein.  J. Virol. 84:1891-1901.

Chandran S. and Machamer C.E2008. Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis.  Traffic 9:1894-1904.

Hogue B.G. and Machamer C.E.2008. Coronavirus structural proteins and virus assembly. Nidoviruses. Edited by S. Perlman, T. Gallagher, and E. Snijder. (ASM), pp. 179-200.

Sbodio J.I. and Machamer C.E2007. Identification of a redox sensitive cysteine residue in GCP60 that regulates its interaction with golgin-160.  J. Biol. Chem 282:29874-29881.

McBride C.E. Li J., and Machamer C.E 2007. The cytoplasmic tail of the spike protein of the severe acute respiratory syndrome coronavirus contains a novel endoplasmic reticulum retrieval signal that binds COPI and promotes interaction with membrane protein. J. Virol., 81:2418-2428.

Hicks S.W. Horn T.A., McCaffery J.M., Zuckerman D.M. and Machamer C.E 2006. Golgin-160 promotes cell surface expression of the beta-1-adrenergic receptor. Traffic 7:1666-1677.

Williams D., Hicks S.W., Machamer C.E., and Pessin J.E. 2006. Golgin-160 is required for the Golgi membrane sorting of the insulin-responsive glucose transporter GLUT4 in adipocytes., Molec. Biol. Cell 17:5346-5355.

Sbodio J.I., Hicks S.W., Simon D., and Machamer C.E 2006. GCP60 preferentially interacts with a caspase-generated golgin-160 fragment. J. Biol. Chem. 281

Youn S., Collisson E.W., and Machamer C.E 2005. Contribution of trafficking signals in the cytoplasmic tail of the infectious bronchitis virus spike protein to virus infection. J. Virol. 79 13209-13217.

Pendleton A.R., and Machamer C.E. 2005. Infectious bronchitis virus 3a protein localizes to a unique punctate domain of the smooth endoplasmic reticulum. J. Virol.,79:6142-6151. PubMed Reference

Hicks S.W. and Machamer C.E. 2005. Golgi structure in stress sensing and apoptosis. Biochim. Biophys. Acta 1744:406-414.

Maag R., Mancini M., Rosen R.A.and Machamer C.E.. 2005. Caspase-resistant golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors. Molec. Biol. Cell 16:3019-2027.