Man-Wah Tan

Administrative Appointments

• Senator-at-Large, School of Medicine Faculty Senate (2006 - 2009)

Honors and Awards

• V Foundation Scholar, V Foundation (2002)
• Basil O'Connor Scholar, March of Dimes (2002)
• Baxter Foundation Scholar, Baxter Foundation (2001)
• Junior Fellow, Harvard Society of Fellows (1997)

Professional Education

Graduate & Fellowship Program Affiliations

• Genetics
• Immunology
• Microbiology and Immunology

Community and International Work

• New biopharmaceuticals against infectious agents, Penang, Malaysia 
• Host responses to virulence factors from B. pseudomallei, Bangi, Malaysia 

Internet Links

• Tan Lab Home Page

Current Research Interests

I am interested in addressing the fundamental questions of how two antagonistic biological systems interact. My system of choice is the interaction between pathogenic bacteria and their metazoan hosts. Pathogenic bacteria constitute a serious threat to global health and have evolved a variety of strategies to defeat their hosts. A critical first line of defense that is evolutionarily conserved across metazoans is the innate immune system. It enables the host to recognize the aggressors and to communicate this information between and within the cells to elicit appropriate responses to pathogens. Innate immunity involves multiplicity of signaling pathways and effector mechanisms that often function redundantly against a broad spectrum of microbial threats. These molecular factors and signaling cascades function cell autonomously within infected tissues or produce extracellular factors to elicit their effects non-cell autonomously on other tissues. For the elucidation of both cell and non-cell autonomous events, and to gain a more holistic understanding of host-pathogen interactions within the context of a whole organism, I pioneered the use of infection of the nematode C. elegans by bacterial pathogens as the experimental system (Tan and Ausubel, 2000). With this system, both C. elegans and pathogen can be genetically altered and the effects of these alterations on pathogenesis or host immunity can be readily tested. We can also tap into the multifaceted power of genetics and genomics to elucidate the molecular and cellular mechanisms underlying host pathogen interactions in vivo. Because the C. elegans body is transparent, we are able assess the effects of loss- or gain- of a host protein function on the progress of infection simply by visualizing and quantifying the accumulation of fluorescently-labeled bacteria within these animals over time. Spatiotemporal changes in host genes expressions and the subcellular localization host proteins can also be assessed over the course of an infection within a live host. In addition, because the TLR-NF-kB axis, the predominant innate immunity pathway in vertebrate and Drosophila, is absent in C. elegans (Pujol et al., 2001), several TLR-independent innate immunity pathways that might otherwise be masked by the TLR-NF-kB pathway have been discovered. Several of these pathways are also involved in other aspects of organismal biology, including aging and stress responses.
Our recent major findings include the identification of GATA transcription factors as playing a conserved role in epithelial immunity (Shapira et al., 2006), the demonstration that specific polyunsaturated fatty acids modulate basal immunity (Nandakumar and Tan, 2008), the elucidation of neuronal signaling in maintenance of immune homeostasis (Kawli and Tan, 2008) and how this neuro-immuno axis could be targeted by pathogens for immune suppression (Evans et al., 2008b). We further showed that although aging and immunity are mediated by DAF-2 insulin-like signaling, they involve distinct mechanisms that engage different serine threonine kinases (Evans et al., 2008a; Kurz and Tan, 2004). Based on these findings, my research program continues to focus on three related areas:
1) Elucidate the molecular mechanism of innate immunity.
a.Identify and characterize of novel innate immunity genes
b.Define the neuronal circuit that maintains immune homeostasis
c.Define the mechanisms by which long chain fatty acids modulate immunity
d.Define immune responses in uterine tissues
2) Define the interactions between bacterial and host immunity factors,
a.Identify and characterize P. aeruginosa and B. pseudomallei factors require for immune suppression.
b.Identify and characterize S. typhimurium factors required for intestinal colonization
3) Differentiate the mechanisms that regulate immunity, stress responses and longevity.

Publications

• It takes nerves to fight infections: insights on neuro-immune interactions from C. elegans. Kawli T, He F, Tan MW. Dis Model Mech. 2010 Nov-Dec; 3 (11-12): 721-31
• Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans. Kawli T, Wu C, Tan MW. Proc Natl Acad Sci U S A. 2010; 107 (31): 13788-93
• Gamma-linolenic and stearidonic acids are required for basal immunity in Caenorhabditis elegans through their effects on p38 MAP kinase activity. Nandakumar M, Tan MW. PLoS Genet. 2008; 4 (11): e1000273
• Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling Kawli T, Tan MW. Nat Immunol. 2008; 9 (12): 1415-24
• Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. Evans EA, Kawli T, Tan MW. PLoS Pathog. 2008; 4 (10): e1000175