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Lopez Laboratory

Virus-Host Interactions and Innate Immunity

Our body, as well as that of all other animals, is equipped with a complex defense system that protects us from microbes that cause disease. Our laboratory studies the signals that turn on and regulate this defense system –the immune system- when we are infected with common viruses, such as the influenza virus or the respiratory syncytial virus. These viruses can cause or exacerbate chronic lung diseases, such as asthma, and can be fatal in some patients. 

The immune response that prevents the virus from growing to dangerous levels and causing disease can be very damaging to our own body if turned on in the absence of real threat from disease-causing microbes; thus, the immune response it is tightly regulated and is only active upon recognition of specific signals from the invading pathogens by specialized cellular proteins. 

By identifying the viral and cellular molecules involved in initiating the immune response during infection and by elucidating how our body protects itself from the ammunitions of the immune system, we hope to contribute to the development of better antiviral treatments and vaccines to protect humans and other animals from these infections.

Ongoing projects

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?

Electron Microscopy of SeV

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

Molecules produced in infected tissue

      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. 
 
Current Members
Carolina Lopez, PhD, Penn Vet

Carolina B. López PhD
Principal Investigator

PhD in Biomedical Sciences
Mount Sinai School of Medicine, NY
lopezca@vet.upenn.edu
Yan Sun, PhD, Penn Vet

Yan Sun, PhD
Postdoctoral Researcher (joined  Jan. 2013)

PhD in Pathobiology
University of Illinois at Urbana-Champaign, Urbana, IL yansun@vet.upenn.edu

Emily Dunay
Undergraduate Student (joined 2011)

School of Arts and Sciences, UPenn
emdunay@sas.upenn.edu

Micah Gilbert, Undergraduate, Penn Vet

Micah Gilbert
Undergraduate Student (joined 2013)

School of Arts & Sciences, UPenn  micahg@sas.upenn.edu
Jennifer Grier, PhD, Penn Vet

Jennifer Grier, PhD
Postdoctoral Researcher (Penn-PORT) (joined Nov. 2013)

University of Pennsylvania
grierjt@mail.med.upenn.edu
Jia Xue, PhD student
 Jia Xue
Visiting Scholar (joined Dic. 2013) PhD Student at the College of Veterinary Medicine, China Agricultural University
xuejia1@vet.upenn.edu
 Jie Xu, Post-doc, Lopez Lab

 Jie Xu, PhD
Postdoctoral Researcher (Joined Jan. 2014)
PhD in Biological Science Georgia State University
 jiexu1@vet.upenn.edu


Past members

Deepika Jain, PhD (2011-2014)
Position: Research Specialist D/Lab Manager.

Won-keun Kim (2008-2013)
Position: Graduate Student
Went to: Research Instructor, Korea University

Xiomara Mercado-López, PhD (2010-2013)
Position: Postdoctoral Fellow, University of Pennsylvania, PAWent to: Assistant Professor, Universidad de Puerto Rico, Campus Arecibo.

Karla Tapia (2008-2012)
Position: Research Specialist C
Went to: Research Technician, Universidad Católica de Chile.

Luis Muñoz (2003-2011)
Position: Research Specialist D, Lab manager
Went to: ImClone, NY

Tamar Hermesh, PhD (2005-2010)
Position: Graduate Student (co-mentor), Mount Sinai School of Medicine, NY
Went to: Postdoctoral Fellow, Rockefeller University, NY

Maria Ines Barria, PhD (2009-2010)
Position: Postdoctoral Fellow, Mount Sinai School of Medicine, NY
Went to: Postdoctoral Fellow, Mount Sinai School of Medicine, NY

Olga Herrera (2009-2010)
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 (2002-2007)
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

2014

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.

2013

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.

2012

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.

2011

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.

2010

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.

2009

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.

Book Chapters

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.


 Recent News About the Lopéz Laboratory

  • Carolina López was awarded an AAI Junior Faculty Travel Grant, IMMUNOLOGY 2014TM.
  • Last publications by the López Lab were featured in the January issue of the Penn Vet Research Newsletter. See the article here.
  • Won's paper was accepted! January, 2014.
  • We welcome Jennifer Grier PhD, Jia Xue, and Jie Xu PhD to our laboratory! 
  • Xiomara's paper was accepted in Vaccine!
  • Karla and Won's paper has been accepted in PLoS Pathogens!
  • Best wishes to Xiomara Mercado-Lopez and Won-keun Kim that went back to their respective countries to continue their careers! August, 2013.
  • Dr. López was awarded the Zoetis Award for Veterinary Research Excellence. See article here
  • CONGRATULATIONS Dr. Won-keun Kim! for his graduation from MSSM on June, 2013.
  • Good luck to Karla Tapia that went back to Chile! and welcome to Yan Sun that joins us as a postdoctoral researcher, January, 2013
  • Kudos to Cristhian Cadena, our summer SIUP student that won an award for his poster presentation at the Annual Biomedical Research Conference for Minority Students!
  • Congratulations to Xiomara Mercado-López Ph.D. and Deepika Jain Ph.D. for winning prizes for their posters at the Vet School Annual Faculty Retreat!, 2012
  • Dr. López was one of 15 young scientists selected to participate in the closed door Herrenhausen Symposium on Viral Pathogenesis, Seeon, Germany, June 4-7, 2012, organized by Nature Medicine.
  • Congratulations to Won-keun Kim for submitting his first manuscript!
  • We welcome Dr. Susan Weiss that has joined the lab for a Sabbatical.
  • The López Lab was featured in the October issue of the Penn Vet Research Newsletter. See the article here.
  • Xiomara Mercado-López was awarded a Research Supplement to Promote Diversity in Health- Related Research Programs, NIH. June, 2011.
  • Won-keun Kim was awarded an AAI Trainee Travel award, AAI, IMMUNOLOGY 2011TM.
  • Carolina López was awarded an AAI Junior Faculty Travel Grant, IMMUNOLOGY 2011TM.