Bas Baaten, Ph.D.

Bas Baaten

Bas Baaten, Ph.D.

Adjunct Assistant Professor

Fax: (858)795-5412

Bas Baaten's Research Focus

Aging, Adaptive Immunity, Host-Pathogen Interactions, Host Defense, Inflammation, Innate Immunity, Extracellular Matrix, Infectious Disease Processes, Virulence Factors
Infectious Diseases, Aging-Related Diseases, Pandemic Influenza
Immune System and Inflammation, Respiratory System, Hematopoietic System
Mouse, Human
Cellular and Molecular Imaging, Gene Knockout (Complete and Conditional), Fluorescence Microscopy, In vivo Modeling

Respiratory viruses are very contagious and pose a severe burden to the health of many people, especially the elderly. Influenza viruses specifically cause an average of 36,000 deaths in yearly epidemics in the USA alone, with sporadic, devastating worldwide pandemics. The Baaten lab studies the establishment and maintenance of immunity to respiratory viruses, such as influenza virus. The research is focused on identifying the mechanisms that govern the balance between immunity and pathology at the nasal and pulmonary mucosa following infection. Insights into these mechanisms will be exploited to modulate responses to provide more effective protection to virulent strains and overcome defective immunity in the elderly.

Bas Baaten's Research Report

Immunity versus pathology

Influenza-associated morbidity and mortality due to yearly epidemics and sporadic, devastating pandemics are a significant health and economic burden. Severe complications arising from highly virulent viruses are associated with rapid, massive inflammatory cell infiltration. Although neutrophils are the predominant cell population recruited to the lung in response to pandemic influenza viruses, the mechanisms by which they gain entry to the respiratory tract remain unclear. We demonstrated a previously unknown contribution of the gelatinase matrix metalloprotease (MMP) 9 to influenza pathogenesis by mediating excessive neutrophil migration into the lung, which not only controls viral replication, but also contributes to morbidity (PLOS Pathogen, 2012). Neutrophil migration was dependent on MMP9 secretion and dependent on toll-like receptor (TLR) signaling in non-hematopoietic cells and was mediated in part by TNFα. Innate recognition of influenza virus therefore provides a mechanism that facilitates recruitment of neutrophils through chemokines and enables their motility within the tissue via MMP9-mediated cleavage of the basement membrane (Movie 1), which could be exploited for therapeutic purposes. 

Movie 1: Neutrophil recruitment to the lung in response to influenza virus infection: (1) TLR signaling in response to influenza virus infection of epithelial cells induces a local chemokine gradient (2) that attracts neutrophils from the periphery (3) Neutrophil motility in the parenchyma following diapedesis is mediated by the proteolytic activity of MMP9, which is controlled by TLR signaling-induced TNFα (4).

We are currently looking into the contribution of MMPs in other cell populations to influenza virus pathogenesis. For example, T cells are crucial in resolving influenza by killing virus-infected cells in the respiratory tissues. T cell migration to the infected respiratory epithelium is crucial for their effector responses. How T cells are induced and maintained, and migrate to infected tissues has important implications in the outcome after viral infection and is of great interest. We showed that T cell immunity to influenza virus is regulated by the adhesion receptor CD44 by regulating T cell survival (Immunity, 2010). The summation of signals to T cells during migration and adhesion to the extracellular matrix can critically impact their development and homeostasis (reviewed in Frontiers in Immunological Memory, 2012). We are currently investigating the role of MMPs in T cell migration and function.

Defective immunity in the elderly

Most natural infections in humans are restricted to the nasal mucosa and the upper respiratory tract and are resolved before causing lung pathology. The Nasal Associated Lymphoid Tissue (NALT) is the first immune tissue that is exposed to inhaled pathogens and is crucial for optimal mucosal immunity. Furthermore, we demonstrated that mucosal adjuvants can enhance and boost immunity to respiratory viruses (European Journal of Immunology, 2006 and Vaccine, 2010). Replication-capable vaccines that specifically target the upper respiratory tract and NALT, such as cold-adapted viruses, mimic natural infection and induce superior cross-reactive immunity compared to inactivated intramuscular vaccines. Very little is known about the requirements for T cell migration to the NALT following influenza virus infection or vaccination. We observed that L-Selectin, among other integrins, is critical for the migration of CD8 T cells to this mucosal site and demonstrated that T cell responses at the mucosal surfaces of the aged NALT were greatly reduced (unpublished observation). We are now identifying the requirements (T cell-intrinsic and environmental defects) for cold-adapted influenza virus-mediated immunity in the aged.


Past and ongoing studies that give new insights into the requirements for cellular immunity during viral pathogenesis could elucidate the balance between protection and pathology. Understanding the mechanisms that lead to effective mucosal immunity therefore has considerable therapeutic relevance. 

Research was made possible by grants from National Institute for Allergy and Infectious DiseasesNational Institute for Aging, and the American Foundation for Aging Research. 

Bas Baaten's Bio

Bas Baaten received his Ph.D. from the Royal Veterinary College at the University of London in 2003 in studies on the interaction of herpes viruses at the respiratory mucosa. He trained as a postdoctoral scientist at the Edward Jenner Institute for Vaccine Research near Oxford (UK) investigating nasal and pulmonary immunity in response to infection with respiratory viruses, such as RSV and influenza A virus. Dr Baaten continued his work on influenza virus pathogenesis at the Sidney Kimmel Cancer Center in San Diego, USA, where he was promoted to Senior Research Scientist in 2007. He joined the Sanford-Burnham Medical Research Institute in 2009 as a Staff Scientist and was appointed as a Research Assistant Professor in 2010. In 2012 he was appointed as an Assistant Professor in the Infectious and Inflammatory Disease Center, Inflammatory Diseases program. Dr Baaten received his first NIH grant in 2008 and has developed a research program on virus-host interactions at the respiratory mucosa with continued extramural funding from research grants from the NIH and the American Foundation for Aging Research.

IPP Accessory


Location, location, location: the impact of migratory heterogeneity on T cell function.

Baaten BJ, Cooper AM, Swain SL, Bradley LM

Front Immunol 2013 Oct 8 ;4:311

CD44 regulates survival and memory development in Th1 cells.

Baaten BJ, Li CR, Deiro MF, Lin MM, Linton PJ, Bradley LM

Immunity 2010 Jan 29 ;32(1):104-15

Show All Select Publications

Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance.

Nakanishi Y, Duran A, L'Hermitte A, Shelton PM, Nakanishi N, Reina-Campos M, Huang J, Soldevila F, Baaten BJG, Tauriello DVF, Castilla EA, Bhangoo MS, Bao F, Sigal D, Diaz-Meco MT, Moscat J

Immunity 2018 Dec 18 ;49(6):1132-1147.e7

Location, location, location: the impact of migratory heterogeneity on T cell function.

Baaten BJ, Cooper AM, Swain SL, Bradley LM

Front Immunol 2013 Oct 8 ;4:311

Identification of small molecules that interfere with H1N1 influenza A viral replication.

Bottini A, De SK, Baaten BJ, Wu B, Barile E, Soonthornvacharin S, Stebbins JL, Bradley LM, Chanda SK, Pellecchia M

ChemMedChem 2012 Dec ;7(12):2227-35

Regulation of Antigen-Experienced T Cells: Lessons from the Quintessential Memory Marker CD44.

Baaten BJ, Tinoco R, Chen AT, Bradley LM

Front Immunol 2012 ;3:23

Harnessing memory adaptive regulatory T cells to control autoimmunity in type 1 diabetes.

Li CR, Baaten BJ, Bradley LM

J Mol Cell Biol 2012 Feb ;4(1):38-47

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