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Olga S. Latinovic, PhD, MSc

Academic Title:

Assistant Professor

Primary Appointment:

Microbiology and Immunology

Location:

Institute of Human Virology, N 615

Phone (Primary):

(410) 706-2769

Fax:

(410) 706-1992

Education and Training

  • 2006: PhD, Lehigh University, PA.
  • 2006-2007: Postdoctoral Fellow, Institute of Human Virology, University of Maryland Biotechnology Institute.
  • 2007-2008: Research Associate, Institute of Human Virology, University of Maryland Biotechnology Institute.
  • 2008-2010: Research Associate, Institute of Human Virology, University of Maryland School of Medicine.
  • 2010-present: Assistant Professor, Institute of Human Virology, University of Maryland School of Medicine, Department for Microbiology and Immunology.

Biosketch

The ability of HIV to develop resistance to antiviral drugs is well documented. This necessitates that researchers take into account the virus’s ability to adapt. Dr. Latinovic’s research focus is on developing novel antiviral therapy strategies that block HIV entry with minimum side effects. By blocking viral entry, infection of new cells is prevented.

A target of great interest is the cellular chemokine co-receptor CCR5 as it plays a critical role in HIV entry. CCR5, a G protein-coupled receptor (GPCR), is the predominant HIV-1 coreceptor during horizontal transmission (i.e. during primary infection) and early stages of HIV spread within infected individuals. It is an especially attractive antiviral target because it is relatively dispensable for normal immune function and human health, which minimizes potential side effects produced by drugs directed at CCR5.

In order to validate such drugs, Dr. Latinovic’s most recent research interest and published work use humanized mouse models that are reconstituted with human hematopoietic cells. These models mimic the natural course of HIV infection in humans and allow for validation of drug treatment in a convenient in vivo model. Ultimately drugs so validated can be candidates for future clinical trials in humans.

Research/Clinical Keywords

HIV-1 Entry Inhibition In Vivo

Highlighted Publications

Y. Affram, J. Zapata, W. Tolbert, W. Zhou, M. Iglesias-Ussel, M. Pazgier, K. Ray, O. S. Latinovic, and F. Romerio, The HIV-1 antisense protein ASP is an integral protein of the viral envelope, Journal of Virology, pii: JVI.00574-19. doi: 10.1128/JVI.00574-19 (2019).

O. S. Latinovic, L. M. Neal, A. Heredia, Y. Tagaya, S. Medina-Moreno, J. C. Zapata, M. Reitz, J. Bryant, R. R. Redfield, Suppression of Active and Persistent HIV-1 Infection in CD34+ Hematopoietic Humanized Mice by Combination of Long Acting cART Therapy and CCR5 Targeting Drugs,  AIDS Research and Human Retroviruses,  doi: 10.1089/AID.2018.0305. (2019).

Yan Zhang, Xuexiang Du, Mingyue Liu, Fei Tang, Peng Zhang, Chunxia Ai, James Fields, Eric Sundberg, Olga S. Latinovic, Martin Devenport, Pan Zheng and Yang Liu, Lysosomal CTLA-4 Degradation Causes Immunotherapy-related Adverse Effect and Restrains Immunotherapeutic Efficacy of Anti-human CTLA-4 Antibodies, Cell Research, doi: doi.org/10.1038/s41422-019-0184-1. (2019).

D. Zella, S. Curreli, F. Benedetti, S. Krishnan, F. Cocchi, O. S. Latinovic, F. Denaro, F. Romerio, M. Djavani, M.E. Charurat, J. L. Bryant, Tettelin H., and R.C. Gallo, Mycoplasma promotes malignant transformation in vivo and its DnaK has broad oncogenic properties, Proceedings of the National Academy of Sciences, 115( 51):E12005-E12014 pii: 201815660. (2018).

O. S. Latinovic, M. Reitz, A. Heredia, CCR5 Inhibitors and HIV-1 Infection, Journal of AIDS, Vol 1, Issue 1 (2018).

Additional Publication Citations

Books

  1. Olga Latinovic, Micromechanics and Structure of Soft and Biological Materials: An Optical Tweezers Study, Verlag Dr. Muller Publishing, ISBN (978-3-639-23050-5), 2010.
  2. Ming-Tzo Wei, O. Latinovic, L. A. Hough, Y.-Q. Chen, H. D. Ou-Yang, A. Chiou, "Studying microrheology of soft and living materials using optical trapping," in Handbook of Photonics for Biomedical Engineering, Kim, Donghyun; Ho, Aaron H.-P.; Somekh, Michael G. (Eds.), Springer-Verlag, Berlin, (2016). ISBN 978-94-007-5053-1.

All Publications

A. Heredia, B. Gilliam, O. Latinovic, N. Le, D. Bamba, A. DeVico, G.B. Melikian, R. C. Gallo and R. R. Redfield, Rapamycin reduces CCR5 density levels on CD4 T cells and this effect results in potentiation of Enfuvirtide (T-20) against R5 HIV-1 in vitro, Antimicrobial Agents and Chemotherapy, Volume 51, No.7, 2489-2496 (2007).

A. Heredia, O. Latinovic, R. C. Gallo, G. B. Melikian, M. Reitz, N. Le and R. R. Redfield, Low doses of Rapamycin enhance the antiviral activity of CCR5 antagonist VCV against wild-type and drug resistant R5 HIV-1, Proceeding of the National Academy of Sciences, Volume 105, No. 51, 20476-20481 (2008).

K. Miyauchi, Y. Kim, O. Latinovic, V. Morozov and G. B. Melikian, HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes, Cell, Volume 137, Issue 3, 433-444 (2009).

O. Latinovic, A. Heredia, Robert C. Gallo, Marv Reitz, Nhut Le and Robert R. Redfield, Low doses of the immunomodulatory drug Rapamycin decrease the anti-HIV effective dose of the CCR5 antagonist Aplaviroc: potential clinical implications, Antiviral Research, Volume 83, 86-89 (2009).

O. Latinovic, J. Kuruppu, C. Davis, N. Lee and A. Heredia, Pharmacotherapy of HIV-1 Infection: Focus on CCR5 antagonist Maraviroc, Review for Clinical Medicine: Therapeutics, Volume 1, 1497-1510 (2009).

O. Latinovic, L. A. Hough and H. D. Ou-Yang, Structural and Micromechanical Properties of Collagen Type I, the Journal of Biomechanics, Volume 43, Issue 3, 500-505 (2010).

O. Latinovic, M. Reitz, N. Le, J. S. Foulke, G. Fatkenheuer, C. Lehmann, H. Valdez, R. R. Redfield and A. Heredia, CCR5 antibodies HGS004 and HGS101 inhibit Maraviroc-resistant HIV-1 and Inhibition is more potent in the presence of Maraviroc: Clinical Implications, Virology, (2011).

N. Jha, O. Latinovic, E. Martin, G. Novitskiy, M, Marin, K. Miyauchi, J. Naughton, J. A. T. Young and G.B. Melikyan, Imaging single retrovirus entry through alternative receptor isoforms and intermediate virus-cell fusion, PloS Pathogens, Volume 7, Issue 1, 1001260 (2011).

O. Latinovic, N. Le, M. Reitz, R. Pal, A. DeVico, J. S. Foulke, R. R. Redfield and A. Heredia, Synergistic Inhibition of CCR5-tropic HIV-1 by Maraviroc and CCR5 Antibody HGS004 in Primary Cells: Potential Implications for Treatment and Prevention, AIDS, 1;25(9):1232-5 (2011).

F. Cocchi, A. L. DeVico, W. Lu, M. Popovic, O. Latinovic, M. M. Sajadi, R. R. Redfield, M. K. Lafferty, M. Galli, A. Garzino-Demo and R. C. Gallo, The Soluble Factors from T Cells Inhibiting X4 Strains of HIV are a Mixture of Beta Chemokines and RNases, Proceeding of the National Academy of Sciences, PMID: 22431590, (2012).

O. Latinovic, K. Schneider, H. Szmacinski, J. R. Lakowicz, A. Heredia and R. R. Redfield, Binding of fusion protein FLSC IgG1 to CCR5 is enhanced by CCR5 antagonist Maraviroc, Antiviral Research, Volume 112: 80-90 (2014).

F. Obata, P. B. Subrahmanyam, A. E. Vozenilek, L. M. Hippler, T. Jeffers, M. Tongsuk, I. Tiper, P. Saha, D. M. Jandhyala,G. L. Kolling, O. Latinovic and T. J. Webb, Natural Killer T (NKT) cells accelerate Shiga toxin type 2 (Stx2) pathology in mice, Frontiers in Microbiology, section Infectious Diseases, doi: 10.3389/fmicb.2015.00262, (2015).

O. Latinovic, S. Medina-Moreno, K. Schneider, N. Gohain, J. Zapata, M. Pazgier, M. Reitz, J. Bryant, R.R. Redfield, Full length single chain Fc protein (FLSC IgG1) as a potent anti-viral therapy candidate: Implications for in vivo studies, AIDS Research and Human Retroviruses - Volume 31, Number 00, (2015).

F. Obata, L. M. Hippler, P. Saha, D. M. Jandhyala and O. Latinovic, Shiga toxin type-2 (Stx2) induces glutamate release via phosphoinositide 3-kinase (PI3K) pathway in murine neurons, Frontiers of Molecular Neuroscience, ISSN: 1662-5099 (2015).

D. Basta, O. Latinovic, M. K. Lafferty, L. Sun, J. Bryant, A. Caruso, R. Gallo, A. Garzino-Demo. Angiogenic, lymphoangiogenic and adipogenic effects of HIV-1 Matrix protein p17 Ugandan variant. Pathogens and Diseases (2015). DOI: http://dx.doi.org/10.1093/femspd/ftv062

O. Latinovic and R.R. Redfield, CCR5-Cellular doorway for HIV-1 Entry. Review for Journal for Human Virology and Retrovirology. 2(5):00056, (2015).

A. Heredia, O.S. Latinovic, F. Barbault, E. P. H. deLeeuw. A Novel Small Molecule Inhibitor of HIV Entry. Drug Design. Development and Therapy. Vol 9, 1-10 (2015).

O.S. Latinovic, J. Zhang, Y. Tagaya, A. L. DeVico, T. Fouts, K. Schneider, J. Lakowicz, A. Heredia and R. R. Redfield, Synergistic inhibition of R5 HIV-1 by Maraviroc and FLSC IgG in primary cells: Implications for prevention and treatment- Current HIV Research, PMID: 26354735, Vol 14, Issue 1, (2016).

O. S. Latinovic, S. Medina-Moreno, L.M. Hippler, J.C. Zapata and R.R. Redfield, Humanized NSG Mouse Models of HIV-1 Infection and Pathogenesis, Review for Journal for Human Virology and Retrovirology, 3 (2): 00087, (2016).

Curreli S, Wong BS*, Latinovic O*, Konstantopoulos K, Stamatos NM, Class 3 semaphorins induce F-actin reorganization in human dendritic cells: Role in cell migration, J Leukoc Biol. (2016) . pii: jlb.2A1114-534R. [Epub ahead of print]

O. S. Latinovic, S. Medina-Moreno, K. Schneider, N. Gohain, J. Zapata, L.M. Hippler, Y. Tagaya, M. Pazgier, M. Reitz, J. Bryant, R.R. Redfield, Full length single chain Fc protein (FLSC IgG1) as a potent anti-viral therapy candidate: Implications for in vivo studies, World Biomedical Frontiers, ISSN: 2328-0166, section of Infection and Immunity (2016)

O. S. Latinovic, M. Reitz, A. Heredia, CCR5 Inhibitors and HIV-1 Infection, Journal of AIDS, Vol 1, Issue 1 (2018).

O. S. Latinovic, S. Medina-Moreno, K. Schneider, N. Gohain, J. Zapata, L.M. Hippler, Y. Tagaya, M. Pazgier, M. Reitz, J. Bryant, R.R. Redfield, Full length single chain Fc protein (FLSC IgG1) as a potent anti-viral therapy candidate: Implications for in vivo studies, World Biomedical Frontiers, ISSN: 2328-0166, section of Infection and Immunity (2016)

D. Zella, S. Curreli, F. Benedetti, S. Krishnan, F. Cocchi, O. S. Latinovic, F. Denaro, F. Romerio, M. Djavani, M.E. Charurat, J. L. Bryant, Tettelin H., and R.C. Gallo, Mycoplasma promotes malignant transformation in vivo and its DnaK has broad oncogenic properties, Proceedings of the National Academy of Sciences, 115( 51):E12005-E12014 pii: 201815660. (2018).

O. S. Latinovic, L. M. Neal, A. Heredia, Y. Tagaya, S. Medina-Moreno, J. C. Zapata, M. Reitz, J. Bryant, R. R. Redfield, Suppression of Active and Persistent HIV-1 Infection in CD34+ Hematopoietic Humanized Mice by Combination of Long Acting cART Therapy and CCR5 Targeting Drugs,  AIDS Research and Human Retroviruses,  doi: 10.1089/AID.2018.0305. (2019).

Yan Zhang, Xuexiang Du, Mingyue Liu, Fei Tang, Peng Zhang, Chunxia Ai, James Fields, Eric Sundberg, Olga S. Latinovic, Martin Devenport, Pan Zheng and Yang Liu, Lysosomal CTLA-4 Degradation Causes Immunotherapy-related Adverse Effect and Restrains Immunotherapeutic Efficacy of Anti-human CTLA-4 Antibodies, Cell Research, doi: doi.org/10.1038/s41422-019-0184-1.  (2019).

Y. Affram, J. Zapata, W. Tolbert, W. Zhou, M. Iglesias-Ussel, M. Pazgier, K. Ray, O. S. Latinovic, and F. Romerio, The HIV-1 antisense protein ASP is an integral protein of the viral envelope, Journal of Virology, pii: JVI.00574-19. doi: 10.1128/JVI.00574-19 (2019).

* Co-authorship

Research Interests

  • Developing novel antiviral therapy strategies that block HIV entry with minimum side effect.
  • Cellular chemokine co-receptor CCR5 as it plays a critical role in HIV entry.
  • The use humanized mouse models, reconstituted with human hematopoietic cells. These models mimic the natural course of HIV infection in humans and allow for validation of drug treatment in a convenient in vivo model.