Our laboratory focuses on the study of the innate immune response to respiratory viruses. We are particularly interested in understanding the early events of the virus-host interaction that determine the quality of the antiviral response and the clinical outcome of the infection. We hope to gather knowledge that will lead to the development of better antiviral therapies and vaccines. We are interested in the following specific areas:
- Identification and characterization of viral features and host molecular mechanisms that determine the onset and quality of the antiviral immune response.
- Characterization of host mechanisms that regulate the antiviral immune response ensuring clearance of the virus while minimizing damage of the host tissue.
Are defective viral genomes the ultimate trigger for antiviral immunity?
We have described a critical role for defective viral genomes (DVGs), which were until recently considered an epiphenomenon of in vitro
virus replication, as primary stimuli for the activation of the antiviral response, both in vitro
and in vivo
. DVGs are generated by a large number of animal and plant viruses, but their role during the virus-host cycle remained speculative. We recently demonstrated that DVGs arise naturally during mouse infection with SeV or with mouse-adapted influenza virus and provide primary danger signals for the initiation of the antiviral response in the lung. We are interested in identifying viral features that confer the potent immunostimulatory activity to DVGs and to harness these motifs for the development of novel adjuvants. We are also interested in characterizing the host pathways involved in the response to DVGs in order to identify potential targets for antiviral therapy. Moreover, we are investigating the role of DVGs in determining the antiviral response during respiratory infections in the human lung in order to establish the role of DVGs in respiratory virus pathogenesis in humans.
Systemic regulation of the lung antiviral response
Upon viral recognition and sensing of the infecting virus, infected cells produce cytokines and chemokines that promote the recruitment and activation of immune cells. We reported that soon after a respiratory infection, molecules produced in the infected lung are transported through the blood to signal cells located in the distal bone marrow. Cells instructed in the bone marrow by type I IFNs produced in the lung and transported to the bone marrow through the blood become resistant to virus infection and respond more efficiently to viral cues when recruited to the lung, therefore enhancing the innate immune response and facilitating the clearance of the virus. We are currently interested in characterizing other mediators of the lung-bone marrow axis and in determining their role during the initial anti-viral response. In particular, we are investigating the regulatory function of innate immune cells that massively infiltrate the lung during infection and that contribute to virus clearance while protecting the tissue for excessive damage.
Carolina B. López PhD
PhD in Biomedical Sciences
Mount Sinai School of Medicine, NY firstname.lastname@example.org
Deepika Jain PhD
Research Specilist D / Lab Manager (joined Nov. 2011)
PhD in Medical Biochemistry
Delhi University, India
Yan Sun, PhD
Postdoctoral Researcher (joined Jan. 2013)
PhD in Pathobiology
University of Illinois at Urbana-Champaign, Urbana, IL email@example.com
Undergraduate Student (joined 2013)
School of Arts & Sciences, UPenn firstname.lastname@example.org
Jennifer Grier, PhD
Postdoctoral Researcher (Penn-PORT) (joined Nov. 2013)
University of Pennsylvania email@example.com
Visiting Scholar (joined Dic. 2013)
PhD Student at the College of Veterinary Medicine, China Agricultural University firstname.lastname@example.org
Jie Xu, PhD
Postdoctoral Researcher (Joined Jan. 2014)
PhD in Biological Science Georgia State University
Position: Graduate Student
Went to: Research Instructor, Korea University Xiomara Mercado-López, PhD
Position: Postdoctoral Fellow, University of Pennsylvania, PA
Went to: Assistant Professor, Universidad de Puerto Rico, Campus Arecibo. Emily Dunay
Position: Undergraduate Student, University of Pennsylvania, PA Karla Tapia
Position: Research Specialist C
Went to: Research Technician, Universidad Católica de Chile. Luis Muñoz
Position: Research Specialist D, Lab manager
Went to: ImClone, NY Tamar Hermesh, PhD
Position: Graduate Student (co-mentor), Mount Sinai School of Medicine, NY
Went to: Postdoctoral Fellow, Rockefeller University, NY Maria Ines Barria, PhD
Position: Postdoctoral Fellow, Mount Sinai School of Medicine, NY
Went to: Postdoctoral Fellow, Mount Sinai School of Medicine, NY Olga Herrera
Position: PREP Student, Mount Sinai School of Medicine, NY
Went to: continue PREP program at Mount Sinai, NY
Current position: Regeneron, NY Jacob Yount, PhD
Position: Graduate Student (co-mentor), Mount Sinai School of Medicine, NY
Went to: Postdoctoral Fellow, Rockefeller University, NY
Current position: Assistant Professor, Center for Microbial Interface Biology, Ohio State university.
Rotation, Summer students, and Undergrads
- Ethan Mack (UPenn, IGG, MD/PhD), Fall 2013
- Alexis Leanza (UPenn, CTSA Internship), Summer 2013
- Cristhian Cadena (UPenn, SUIP), Summer 2012 and 2013
- Lakshmi Bhagavathula (UPenn, Master in Biotechnology), Summer-Fall 2012
- Tori Yamamoto (UPenn, IGG), Fall 2012
- Julia Rood (UPenn, IGG, MD/PhD), Fall 2012
- Joshua Sherman (UPenn, Vagelos Program in Life Sciences & Management), Spring 2012
- Steven Siegel (UPenn, MVP, MD/PhD), Fall 2011
- Megan Wise (UPenn, MVP), Fall 2011
- Jerome Molleston (UPenn, MVP, MD/PhD), Summer and more 2011
- Michael Adu (UPenn, SUIP), Summer 2011
- Sabrina Tsang (UPenn, MVP), Spring 2011-Fall 2012
- Ciara Gimblet (UPenn, MVP), Spring 2011
- Gretchen Harms (UPenn, IGG), Winter 2011
- Zachary Zalinger (UPenn, MVP), Winter 2011
Google Scholar Link
Kim WK, Jain D, Sánchez MD, Koziol-White C, Matthews K, Ge M, Haczku A, Panettieri RA, Frieman MB, and López CB. (2014) Deficiency of Melanoma Differentiation-associated protein 5 results in Exacerbated Chronic Post-Viral Lung Inflammation. Am. J. Respir. Crit. Care Med. 189(4):437-48. doi: 10.1164/rccm.201307-1338OC. PMID: 24417465.
Tapia K, Kim WK, Sun Y, Mercado-López X, Dunay E, Wise M, Adu M, and López CB. (2013) Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity. PLoS Pathog 9(10): e1003703. doi:10.1371/journal.ppat.1003703. * Featured Article. *Co-first authors.
Mercado-López M, Cotter CR, Kim WK, Muñoz L, Sun Y, Tapia K, and López CB. (2013) Highly Immunostimulatory RNA Derived from a Sendai Virus Defective Viral Genome. Vaccine. 2013 Oct 4. pii: S0264-410X(13)01294-2. doi: 10.1016/j.vaccine.2013.09.040. [Epub ahead of print] PMID: 2409987.
Hermesh T, Moran TM, Jain. D, and López CB. (2012) Granulocyte colony-stimulating factor protects mice during respiratory virus infections. PLoS One 7(5): e37334. doi:10.1371/journal.pone.0037334. PMID: 22615983 PMCID: PMC3353936.
Harty RN, Schmitt AN, Bouamr F, López CB and Krummenacher C. (2011) Virus Budding/Host Interactions. Advances in Virology-Editorial. EPub doi:10.1155/2011/963192.
Neil RC, Tapia KA, Dandapani A, MacArthur BD, López C, Ma’ayan A. (2011). Stochastic model of virus and defective interfering particle spread across mammalian cells with immune response. Q-bio.PE, arXiv:1108.4901.
Cotter C, Kim WK, Nguyen M, Yount J, López CB, Blaho, and Moran TM. (2011) The Virion Host Shut-off (vhs) Protein of HSV-1 Blocks the Replication-Independent Activation of NF-κB in Dendritic Cells. J. Virol. Sept 21, EPub Ahead of Print. PMID: 2193765.
López CB and Hermesh T. (2011) Systemic Responses During Local Viral Infections: Type I IFNs Sound the Alarm (Review). Curr. Opin. Immunol 23(4):495-9. PMID: 21752617 PMCID: PMC3163724.
Zhang J, Zhang Y, Dutta D, Argaw AT, Bonnamain V, Seto J, Braun DA, Zameer A, Hayot F, López CB, Raine CS and John GR (2011) Pro- and Anti-apoptotic Actions of Stat1 versus Stat3 Underlie Neuroprotective and Immunoregulatory Functions of Interleukin-11. J. Immunol. 187:1129-1141. PMID: 21709156.
Leung LW, Park M, Martinez O, Valmas C, López CB, and Basler CF. (2011) The Ebolavirus VP35 Protein Suppresses Interferon Production from Conventional but not Plasmacytoid Dendritic Cells. Immunology and Cell Biology. EPub ahead of print. 25 Jan. PMID: 21263462.
Hu J, Nudelman G, Shimoni Y, Kumar M, Ding Y, López C, Hayot F, Wetmur JG, Sealfon SC. (2011) Role of Cell-to-Cell Variability in Activating a Positive Feedback Antiviral Response in Human Dendritic Cells. PLoS One. 2011 Feb 8;6(2):e16614.
Hermesh T, Moltedo B, López CB and Moran TM. (2010) Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses-Review. Viruses 2:2541-2558. PMID: 21994630 PMCID: PMC3185581.
Yount JS, Moltedo B, Yang Y, Charron G, Moran TM, López CB and Hang HH. (2010) Palmitoylome profiling reveals S-palmitoylation-dependent anti-viral activity of IFITM3. Nature Chem. Biol. 6:610-614. PMID: 20601941 *Evaluated in the Faculty of 1000 website.
Hermesh T, Moltedo B, Moran TM and López CB. (2010) Antiviral Instruction of Bone Marrow Leukocytes during Respiratory Viral Infections. Cell Host & Microbe.7:343-353. PMID: 20478536. PMCID: PMC2874206 * Featured Article and Previewed.
Cotter C, Nguyen ML, López CB, Blaho JA and Moran TM. (2010) Virion-Associated Vhs Protein Blocks the Activation of Human Dendritic Cells during a Productive HSV-1 Infection. Plos One. 5:e8684. PMCID: PMC2823768.
Gurfein TB, Zhang Y, López CB, Argaw AT, Zameer A, Moran TM and John GR. Interleukin-11 Regulates Autoimmune Demyelination (2009). J Immunol. 183:4229-4240. PMID: 19734214.
Moltedo B, López CB, Pazos M, Becker MI, Hermesh T and Moran TM. (2009) Cutting Edge: stealth Influenza Virus Replication Precedes the Initiation of Adaptive Immunity. J Immunol. 183:3569-3573. PMID: 19717515.
2008 and before
Escribese MM, Kraus T, Rhee E, Fernandez-Sesma A, López CB and Moran TM. (2008) Estrogen Inhibits Dendritic Cell Maturation to dsRNA Viruses. Blood. 112:475-84. PMID: 18802009, PMCID: PMC2597128.
Yount JS, Gitlin L, Moran TM and López CB. (2008) MDA5 Participates in the Detection of Paramyxovirus Infection and is Essential for the Early Activation of DCs in Response to SeV DI Particles. J. Immunol. 180:4910-4919. PMID: 18354215.
Yount JS, Moran TM and López CB. (2007) Cytokine-Independent Upregulation of MDA5 in Viral Infection. J. Virol. 81:7316-7319. PMID: 17475649, PMCID: PMC1933291.
Yount JS, Kraus T, Horvath C, Moran TM and López CB. (2006) A Novel Role for Defective Interfering Particles in Enhancing Dendritic Cell Maturation. J. Immunol. 177:4503-4513. PMID: 16982887.
López CB, Yount JS, Hermesh T and Moran TM. (2006) Sendai Virus Infection Induces Efficient Adaptive Immunity Independently of Type I IFNs. J. Virol. 80:4538-4545. PMID: 16611914, PMCID: PMC1472017.
López CB, Yount JS and Moran TM. (2006) Minireview. TLR-independent Triggering of Dendritic Cell Maturation by Viruses. J. Virol. 80:3128-3134. PMID: 16505141, PMCID: PMC1440398.
Trumpfheller C, Finke JS, López CB, Moran TM, Moltedo B, Soares H, Huang Y, Schesinger S, Park CG, Nussenzweig MC, Granelli-Piperno A, Steinman RM. (2006) Intensified and Protective CD4+ T Cell Based Immunity at a Mucosal Surface Induced in Mice with Anti-dendritic Cell HIV gag Fusion Antibody Vaccine. J. Exp. Med. 203:607-617. PMCID: PMC2118242.
López CB, Moltedo B, Alexopoulou L, Bonifaz L, Flavell R and Moran T (2004). TLR-Independent Induction of Dendritic Cell Maturation and Immunity by Negative Stranded RNA Viruses. J. Immunol. 173:6882-6889. PMID: 15557183. *Evaluated in the Faculty of 1000 website.
Silva MA, López CB, Rivertin F, Oligny L, Menezes J and Seidman E (2004). Characterization and Distribution of Colonic Dendritic Cells in Paediatric Crohn’s Disease. Inf. Bowel Dis.10:504-512. PMID: 15472509.
López CB, Garcia-Sastre A, Williams BRG and Moran T (2003). The Type I Interferon Pathway, but Not the Secreted Interferon, Participates in the Maturation of Dendritic cells Induced by Negative Stranded RNA Viruses. J Inf. Dis., 187:1123-1136. PMID: 12660927.
López CB, Moran TM, Schulman JL, and Fernandez-Sesma A (2002) Antiviral Immunity and the Role of Dendritic Cells. Int. Rev. Immunol. 21:339-353. PMID: 12486818.
López CB, Fernandez-Sesma A, Schulman J and Moran T (2001) Myeloid Dendritic Cells Stimulate Both Th1 and Th2 Immune Responses depending on the Nature of the Antigen. J. Interf. Cytok. Res.21:763-773. PMID: 11576470.
López CB, Fernandez-Sesma A, Czelusniak S, Schulman J and Moran T (2000) A Mouse Model for immunization with Ex-Vivo Virus-Infected Dendritic Cells. Cell. Immunol. 206:107-115. PMID: 11161442.
López CB, Rao DT, Freiner H, Shapiro R, Marks J and Frey A (1998) Repression of Interleukin-2 mRNA Translation in Primary Human Breast Carcinoma Tumor Infiltrating Lymphocytes. Cell. Immunol. 190:141-155. PMID: 9878115.
López CB, Kalergis AM, Becker MI, Garbarino JA and De Ioannes AE (1998). CD8+ T Cells are the Effectors Cells of the Contact Dermatitis Induced by Urushiol in Mice and are Regulated by CD4+ T Cells. Int. Arch. Allergy and Immunol. 117:194-201. PMID: 9831807.
Kalergis AM, López CB, Díaz MI, Becker MI, Garbarino JA and De Ioannes AE (1997) Modulation by Clofibrate and Tetradecyl Glycidic Acid of the Contact Dermatitis Induced in Mice by an Urushiol Related Allergen 3-Pentadecyl (10-enyl) Cathecol. J. of Invest. Dermat. 108: 57-61. PMID: 8980288.
Moran T.M and López CB. (2009) Host Immune Response to Influenza Virus in “RNA Viruses: Host gene response to Infection” Decheng Yang, Editor. World Scientific Publishing, Vancouver, BC, Canada.