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Maria Cecilia Marcondes, Ph.D.

Assistant Professor Adjunct
Department of Neuroscience
California Campus
Scripps VIVO Scientific Profile
cmarcond@scripps.edu
(858) 784-7447

Scripps Research Joint Appointments

Assistant Professor, Department of Molecular and Cellular Neuroscience

Other Joint Appointments

American Association of Immunology
Society for Neurosciences
Society on NeuroimmunePharmacology

Research Focus

 

The interface between the Immune System and the Central Nervous System

The Central Nervous System (CNS) is susceptible to inflammation and also contributes to the development of inflammatory processes in response to local and peripheral insults. CNS glial cells, microglia and astrocytes, are early responders to infection and injury, quickly modifying the production of inflammatory mediators, cytokines, free radicals, as well as neurothrophic factors. Glial cells contribute to the recruitment of peripheral immune and inflammatory cells, which further activate glial cells, and impact function and viability of neurons, ultimately affecting cognitive functions, behavior, body temperature, and circadian rythm.

Viral infections of the CNS can affect glial cells and the immune environment in the CNS, producing acute and chronic neurological symptoms. This is the case for the Human Immunodeficiency Virus (HIV).  HIV crosses the blood brain barrier in the first few weeks after infection, carried by macrophages. Once in the brain, it productively infects microglia and perivascular macrophages, and the responses triggered by HIV are a double edged swords, with damaging, but also beneficial effects. Importantly, HIV-associated neurocognitive disorders and neuroAIDS, are not decreased by antiretroviral therapies, and for this reason, HIV+ individuals that now live longer, still experience a high incidence of CNS consequences. In fact, aging is one of the factor that can aggravate neurological outcomes in HIV-infected individuals. On the other hand, HIV may trigger several mechanisms that are common to, and accelerate the aging process. The Marcondes Lab examines mechanisms epigenetic mechanisms that are common between HIV and aging in glial cells.

Another factor that can aggravate CNS dysfunction in HIV infection is drug abuse. A drug of special concen is methamphetamine, which is cheap and fast growing, and also highly addictive. The epidemiology of methamphetamine abuse and of HIV infection highly overlap. Drug abusers are more likely to become exposed to HIV due to risk behaviors. We have previously shown that methamphetamine increases the abundance and activation of HIV target cells in the CNS, increasing the reservoir and aggravating inflammatory pathology. The Marcondes Lab is highly focused on how methamphetamine, directly, through the induction of second messengers such as cyclic AMP and free radicals, or to its ability to increase dopamine in vivo, modulates infiltrating macrophages and glial cells to become inflammatory and bear HIV productive infection.

Methamphetamine alone has several deleterious consequences to the brain, but it also affects the core body temperature, producing an often lethal hyperthermia. This condition has the participation of free radicals in peripheral thermogenic sites, such as the brown adipose tissue. The Marcondes Lab examines oxidative stress-mediated mechanisms that affect body temperature by modifying thermogenic programs centrally and in the brown fat.

 

Education

B.Sc., UNISA - Sao Paulo, Brazil, 1987
M.Sc., Philosophy, Universidade de Sao Paulo, Conselho Nacional de Pesquisa, CNPq, Brazil, 1992
Ph.D., Immunology, Universidade de Sao Paulo, FundaƧao de Amparo 'a Pesquisa do Estado de Sao Paulo, FAPESP, Brazil, 1996

Professional Experience

*1986-1987 Biologist: Salck Industria e Comércio de Produtos Biológicos, Sao Paulo, Brazil, Department of Immune-Diagnosis Research.
*1987-1992 Science Instructor: Estaçao Ciencia (Science Museum) – Lapa – Sao Paulo, Brazil.
*1992-1997 Faculty: Immunology, Universidade Cidade de São Paulo (UNICID), São Paulo, Brasil.
*1997-1999 Post-doc: New York University Medical Center, Skirball Institute of Molecular Medicine, Department of Molecular Pathogenesis, Sponsored by Dr. Juan Lafaille, Project: " Cells and molecules involved in the regulation of Experimental Autoimmune Encephalomyelitis and Spinal Cord Lesions".
*1999-2005 Post-doc, The Scripps Research Institute, Department of Neuropharmacology.
*2005-2011 Staff Scientist - The Scripps Research Institute, Molecular and Integrative Neurosciences Department.
*2011-2013 Assistant Professor - The Scripps Research Institute, Molecular and Integrative Neurosciences Department.
*2013-present Assistant Professor - The Scripps Reseach Institute, Molecular and Cellular Neurosciences Department.
*2015 - Lecturer, Interdisciplinary Research Fellowship in NeuroAIDS, at the University of California, San Diego, CA

Awards & Professional Activities

2005 Award Brazilian Society of Immunology – Sao Paulo, Brazil.
2006 Award International Society of Neuroimmunology  – Nagoya, Japan.
2008 Junior Scientist award – 26th Non Human Primate Models of AIDS – San Juan, Puerto Rico.

Selected References

All Publications

Najera JA, Bustamante EA, Bortell N, Morsey B, Fox H, Ravasi T, Marcondes MC. Methamphetamine abuse affects gene expression in brain-derived microglia of SIV-infected macaques to enhance inflammation and promote virus targets. BMC Immunology. 2016; 17(1):7. doi: 10.1186/s12865-016-0145-0

Bortell N, Najera NA, Sanchez-Alavez M, Marcondes MC. In vivo effects of methamphetamine on brown fat reactive oxygen species and mitochondria. Temperature (Austin), 2015, 2(4): 453. Doi: 10.1080/23328940.2015.1091874

Mediouni S, Marcondes MC, Miller C, McLaughlin JP, Valente ST. The cross-talk of HIV-1 Tat and methamphetamine in HIV-associated neurocognitive disorders. Front Microbiol. 2015 Oct 23;6:1164. doi: 10.3389/fmicb.2015.01164. 2015. Review. PMID: 26557111

Marcondes MC, Morsey B, Emanuel K, Lamberty BG, Flynn CT, Fox HS. CD8+ T cells maintain suppression of simian immunodeficiency virus in the central nervous system. J Infect Dis. 211(1):40-4, 2015; doi: 10.1093/infdis/jiu401. PMID: 25035516

Bortell, N.; Morsey, B.; Basova, L.; Fox, H, Marcondes, MC.  Phenotypic changes in the brain of SIV-infected macaques exposed to methamphetamine parallel macrophage activation patterns induced by the common gamma-chain cytokine system. Front Microbiol., 6: 900, 2015; Doi: 10.3389/fmicb.2015.00900.

Sanchez-Alavez M, Conti B, Wood MR, Bortell N, Bustamante E, Saez E, Fox HS and Marcondes MCG (2013) ROS and sympathetically mediated mitochondria activation in brown adipose tissue contribute to methamphetamine-induced hyperthermia. Front. Endocrinol. 4:44. doi: 10.3389/fendo.2013.00044

Marcondes MC, Spina C, Bustamante EA and Fox HS. Increased Toll-like receptor signaling pathways characterize CD8 cells in rapidly progressive SIV infection. BioMed Research International, 2013, 2013: 796014, PMID: 23484159.

Marcondes MC, Morrison BE, Nomura DK, Sanchez-Alavez M, Sanchez-Gonzalez A, Saar I, Kim KS, Bartfai T, Maher P, Sugama S, Conti B. IL-13Ra1 Expression in Dopaminergic Neurons Contributes to Their Oxidative Stress–Mediated Loss following Chronic Systemic Treatment with Lipopolysaccharide. J Immunol. 2012 Dec 15;189 (12):5498-502. Epub 2012. PMID: 23169588.

Marcondes MC, Zhukov V, Bradlow H, Sanchez-Alavez M, Gonzalez AS, Curtiss LK,  Conti B. Effects of chronic mental stress and atherogenic diet on the immune inflammatory environment in mouse aorta. Brain Behav Immun. 2011 Nov;25(8):1649-57. Epub 2011 Jun 22. PubMed PMID: 21722726; PubMed Central PMCID:PMC3191305.

Marcondes MC, Flynn C, Watry DD, Zandonatti M, Fox HS. Methamphetamine increases brain viral load and activates natural killer cells in simian immunodeficiency virus-infected monkeys. Am J Pathol. 2010 Jul;177(1):355-61. Epub 2010 May 20. PubMed PMID: 20489154; PubMed Central PMCID: PMC2893678.

Marcondes MC, Flynn C, Huitron-Rezendiz S, Watry DD, Zandonatti M, Fox HS. Early antiretroviral treatment prevents the development of central nervous system abnormalities in simian immunodeficiency virus-infected rhesus monkeys. AIDS. 2009 Jun 19;23(10):1187-95. PubMed PMID: 19455015; PubMed Central PMCID: PMC2698130.

Furtado GC, Marcondes MC, Latkowski JA, Tsai J, Wensky A, Lafaille JJ. Swift  entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis. J Immunol. 2008 Oct 1;181(7):4648-55. PubMed PMID: 18802067.

Marcondes MC, Watry D, Zandonatti M, Flynn C, Taffe MA, Fox H. Chronic alcohol consumption generates a vulnerable immune environment during early SIV infection in rhesus macaques. Alcohol Clin Exp Res. 2008 Sep;32(9):1583-92. Epub  2008 Jul 9. PubMed PMID: 18616669; PubMed Central PMCID: PMC2579901.

Marcondes MC, Burdo TH, Sopper S, Huitron-Resendiz S, Lanigan C, Watry D, Flynn C, Zandonatti M, Fox HS. Enrichment and persistence of virus-specific CTL in the brain of simian immunodeficiency virus-infected monkeys is associated with a unique cytokine environment. J Immunol. 2007 May 1;178(9):5812-9. PubMed PMID: 17442965.

Marcondes MC, Furtado GC, Wensky A, Curotto de Lafaille MA, Fox HS, Lafaille  JJ. Immune regulatory mechanisms influence early pathology in spinal cord injury and in spontaneous autoimmune encephalomyelitis. Am J Pathol. 2005 Jun;166(6):1749-60. PubMed PMID: 15920160; PubMed Central PMCID: PMC1602407.

Marcondes MC, Burudi EM, Huitron-Resendiz S, Sanchez-Alavez M, Watry D, Zandonatti M, Henriksen SJ, Fox HS. Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection. J Immunol. 2001 Nov 1;167(9):5429-38. PubMed PMID: 11673562.