Denise M. Monack

Honors and Awards

• Sidney Raffel Award for Outstanding Accomplishment in Graduate Study, Stanford University (2001)
• Terman Fellowship, Terman Fellows Program (10/1/08-9/30/11)
• Baxter Faculty Scholar Award, Baxter Foundation (May 2008)

Professional Education

• Ph.D., Stanford University Microbiology & Immunology (2002)

Postdoctoral Advisees

• Zahra Belhocine, Petr Broz, Laura McLaughlin, Thomas Ruby

Research Interests

The primary focus of my research is to understand the genetic and molecular mechanisms of intracellular bacterial pathogenesis. We use two model systems, Salmonella typhimurium and Francisella tularensis, to study the complex host-pathogen interactions.
Both of these organisms survive and multiply in macrophages, an important immune effector cell. Macrophages express Pattern Recognition Receptors on the surface as well as in the cytosol. My laboratory focuses on the cytosolic recognition of bacteria that leads to Type I Interferon signaling and Inflammasome activation. We take both a genetic and biochemical approach to understand the molecular mechanisms involved in host recognition pathways leading to inflammation and pathogen evasion mechanisms.
Salmonella typhi causes the systemic disease typhoid fever and Francisella tularensis causes the systemic disease tularemia (“rabbit fever”). Utilizing mouse models of systemic salmonellosis and tularemia, we would like to understand how Salmonella persists within certain hosts for years in the face of a robust immune response and how F. tularensis, a stealth invader, can cause a rapid, lethal infection.

Publications

• Identification of fevR, a novel regulator of virulence gene expression in Francisella novicida. Brotcke A,  Monack DM.  Infect Immun.  2008; 76 (8): 3473-80
• Host transmission of Salmonella enterica serovar Typhimurium is controlled by virulence factors and indigenous intestinal microbiota. Lawley TD,  Bouley DM, Hoy YE, Gerke C, Relman DA, Monack DM.  Infect Immun.  2008; 76 (1): 403-16
• Activation of the inflammasome upon Francisella tularensis infection: interplay of innate immune pathways and virulence factors. Henry T,  Monack DM.  Cell Microbiol.  2007; 9 (11): 2543-51
• Type I interferon signaling is required for activation of the inflammasome during Francisella infection. Henry T,  Brotcke A, Weiss DS, Thompson LJ, Monack DM.  J Exp Med.  2007; 204 (5): 987-94
• In vivo negative selection screen identifies genes required for Francisella virulence. Weiss DS,  Brotcke A, Henry T, Margolis JJ, Chan K, Monack DM.  Proc Natl Acad Sci U S A.  2007; 104 (14): 6037-42
• Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse. Lawley TD,  Chan K, Thompson LJ, Kim CC, Govoni GR, Monack DM.  PLoS Pathog.  2006; 2 (2): e11
• The inflammasome: a key player in the inflammation triggered in response to bacterial pathogens. Monack DM,  J Pediatr Gastroenterol Nutr.  2008; 46 Suppl 1 E14
• Francisella tularensis: activation of the inflammasome. Weiss DS,  Henry T, Monack DM.  Ann N Y Acad Sci.  2007; 1105 219-37
• Identification of MglA-regulated genes reveals novel virulence factors in Francisella tularensis. Brotcke A,  Weiss DS, Kim CC, Chain P, Malfatti S, Garcia E, Monack DM.  Infect Immun.  2006; 74 (12): 6642-55
• Mig-14 is an inner membrane-associated protein that promotes Salmonella typhimurium resistance to CRAMP, survival within activated macrophages and persistent infection. Brodsky IE,  Ghori N, Falkow S, Monack D.  Mol Microbiol.  2005; 55 (3): 954-72
• Persistent bacterial infections: the interface of the pathogen and the host immune system. Monack DM,  Mueller A, Falkow S.  Nat Rev Microbiol.  2004; 2 (9): 747-65
• Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFNgamma neutralization. Monack DM,  Bouley DM, Falkow S.  J Exp Med.  2004; 199 (2): 231-41
• virK, somA and rcsC are important for systemic Salmonella enterica serovar Typhimurium infection and cationic peptide resistance. Detweiler CS,  Monack DM, Brodsky IE, Mathew H, Falkow S.  Mol Microbiol.  2003; 48 (2): 385-400
• Modulation of virulence by two acidified nitrite-responsive loci of Salmonella enterica serovar Typhimurium. Kim CC,  Monack D, Falkow S.  Infect Immun.  2003; 71 (6): 3196-205
• Salmonella-induced macrophage death: the role of caspase-1 in death and inflammation. Monack DM,  Navarre WW, Falkow S.  Microbes Infect.  2001 Nov-Dec; 3 (14-15): 1201-12
• Actin-based motility is sufficient for bacterial membrane protrusion formation and host cell uptake. Monack DM,  Theriot JA.  Cell Microbiol.  2001; 3 (9): 633-47
• The making of a gradient: IcsA (VirG) polarity in Shigella flexneri. Robbins JR,  Monack D, McCallum SJ, Vegas A, Pham E, Goldberg MB, Theriot JA.  Mol Microbiol.  2001; 41 (4): 861-72
• Salmonella pathogenicity island 2-dependent macrophage death is mediated in part by the host cysteine protease caspase-1. Monack DM,  Detweiler CS, Falkow S.  Cell Microbiol.  2001; 3 (12): 825-37
• Apoptosis as a common bacterial virulence strategy. Monack D,  Falkow S.  Int J Med Microbiol.  2000; 290 (1): 7-13
• Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model. Monack DM,  Hersh D, Ghori N, Bouley D, Zychlinsky A, Falkow S.  J Exp Med.  2000; 192 (2): 249-58
• Macrophage-dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Cirillo DM,  Valdivia RH, Monack DM, Falkow S.  Mol Microbiol.  1998; 30 (1): 175-88
• Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection of mice. Monack DM,  Mecsas J, Bouley D, Falkow S.  J Exp Med.  1998; 188 (11): 2127-37
• Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Monack DM,  Mecsas J, Ghori N, Falkow S.  Proc Natl Acad Sci U S A.  1997; 94 (19): 10385-90
• Salmonella typhimurium invasion induces apoptosis in infected macrophages. Monack DM,  Raupach B, Hromockyj AE, Falkow S.  Proc Natl Acad Sci U S A.  1996; 93 (18): 9833-8