Assistant Professor, Department of Pathobiology, University or Pennsylvania

Penn Institute for Immunology, University of Pennsylvania

Immunology Graduate Group, University of Pennsylvania

Cell and Molecular Biology Graduate Group (MVP Program), The University of Pennsylvania

Research Areas: Antiviral immune responses, Dendritic cells, Infectious Disease, Lung immunity, Viral infections, Virus-host interaction, Innate immunity, Inflammatory responses, Respiratory,
PubMed Link
Contact Information:
School of Veterinary Medicine,
Department of Pathobiology,
Hill Pavilion 318,
380 South University Ave.

 Phone 215-573-3493
 Email lopezca@vet.upenn.edu

Our laboratory focuses on the study of the innate immune response to well-adapted 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:

a. Identification and characterization of viral features and host molecular mechanisms that determine the onset and quality of the antiviral immune response.

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.

b. Characterization of host mechanisms that regulate the antiviral immune response ensuring clearance of the virus while minimizing damage of the host 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.

Micah Gilbert (Undergraduate Student); Emily Dunay (Undergraduate Student); Yan Sun PhD (Postdoc); Jennifer Grier PhD (postdoc); Jie Xu PhD (postdoc); Deepika Jain PhD (Lab Manager); Jia Xue (Student, Visiting Scholar).

Visit http://www.lopezlab.org for up to date information

Benitez AA, Panis M, Xue J, Shim JV, Varble A, Frick AL, López CB, Sachs D, and tenOever BR In vivo RNAi screening identifies MDA5 as a contributor to the cellular defense against influenza A virus Cell Reports 11: 1714-26, 2015.

Sun Y, Jain D, Koziol-White CJ, Genoyer E, Gilbert M, Tapia K, Panettieri RA, Hodinka RL, and López CB Immunostimulatory Defective Viral Genomes Promote Strong Innate Antiviral Responses During Respiratory Syncytial Virus Infection in Mice and Humans PLOS Pathogens In Press: , 2015.

López CB Defective viral genomes: critical danger signals of viral infections (Gem-Review) J Virol 88: 8720-3, 2014.

Kim WK, Jain D, Sánchez MD, Koziol-White CJ, Matthews K, Ge MQ, Haczku A, Panettieri RA Jr, Frieman MB, López CB. Deficiency of MDA5 Results in Exacerbated Chronic Post-Viral Lung Inflammation. Am J Respir Crit Care Med. 189: 437-48, 2014.

Mercado-López X, Cotter CR, Kim WK, Muñoz L, Tapia K, and López CB. Highly Immunostimulatory RNA Derived from a Sendai Virus Defective Viral Genome. Vaccine 31(48): 5713-21, 2013.

Tapia K, Kim WK, Sun Y, Mercado-López X, Dunay E, Wise M, Adu M, and López CB Defective Viral Genomes Arising In Vivo Provide Critical Danger Signals for the Triggering of Lung Antiviral Immunity. PLoS Pathogens 9(10): e1003703, 2013.

Hermesh T, Moran TM, Jain. D, and López CB. Granulocyte colony-stimulating factor protects mice during respiratory virus infections. PLoS One 7(5):e37334: , 2012.

López CB and Hermesh T Systemic Responses During Local Viral Infections: Type I IFNs Sound the Alarm Curr.Opi. Immunol. 23: 495-9, 2011.

Hermesh Tamar, Moltedo Bruno, Moran Thomas M, López Carolina B Antiviral instruction of bone marrow leukocytes during respiratory viral infections. Cell host & microbe 7: 343-53, 2010.

Yount Jacob S, Gitlin Leonid, Moran Thomas M, López Carolina B MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai Virus defective interfering particles. Journal of immunology (Baltimore, Md. : 1950) 180: 4910-8, 2008.

Bs/Ms (Biochemistry) Pontificia Universidad Catolica de Chile, 1996

PhD (Biomedical Sciences) Mount Sinai School of Medicine, 2002