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Mimi  Shirasu-Hiza
Mimi Shirasu-Hiza
Assistant Professor, Genetics and Development


Address: 701 West 168th Street HHSC 1604 New York NY 10032
Phone: 212-305-4186
Fax: 212-923-2090
E-mail:

ms4095@columbia.edu

Education and Training:
Ph.D. 2003, University of California, San Francisco
Postdoctoral Fellow 2004-2009, Stanford University
Affiliations:
bullet  Genetics and Development
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Training Activities:
bullet  Genetics and Development
Research Summary:
(800 words, max)
Circadian-regulated immunity: how does your circadian clock help you fight infection?
Current Research:
Our laboratory aims to understand how the circadian clock regulates specific immune functions using Drosophila melanogaster. Circadian rhythm, or the oscillation of biological functions over the 24 hour day, is increasingly recognized as an important factor in human health. Many diseases have a circadian component, particularly inflammatory diseases. For example, you are most likely to have a heart attack at 8 am, flares of rheumatoid arthritis at 6 am, and an asthma attack at 4 am. However, the molecular mechanisms underlying circadian-regulated physiologies of the immune system and their role in protecting us against bacterial infection remain unclear.

We have found that, in the fly, circadian mutants are immunocompromised against bacterial pathogens and that the immunity of wild-type flies oscillates with circadian rhythm: flies have different survival times depending on the time of day that they are infected. Our overarching goal is to use circadian biology as a prism to understand the interaction, coordination, and regulation of complex physiologies in the whole animal that contribute to survival after bacterial infection. The lab is currently focused on two major projects:

1) Neuroimmunity: Using quantitative live fluorescence imaging in adult flies, we found that specific aspects of immune cell function oscillate with circadian rhythm. This oscillation is lost in circadian mutant flies, including flies defective in circadian clock neurons. We are using fly genetics and fluorescence imaging to identify the signals and pathways underlying this neuroimmune communication from the the nervous system to peripheral immune cells.

2) Novel circadian-regulated immune mechanisms: We found that circadian proteins regulate two different types of immunity, resistance and tolerance. Resistance mechanisms increase survival after infection by restricting microbial growth. Tolerance mechanisms increase the organism's ability to tolerate the pathogenic effects of infection. Our goal is to obtain a comprehensive molecular description of circadian-regulated immunity in Drosophila, including both resistance and tolerance mechanisms that together represent the full range of immune responses to infection.

Drosophila is a powerful system for rapid gene identification. Due to the high level of molecular and mechanistic conservation with vertebrate innate immunity, this work will provide a basis for the investigation of related vertebrate proteins that serve similar immune functions and may be potential targets for therapeutics to increase immunity against infection.

Publications:
(6 max)
1. M. Shirasu-Hiza, D.S. Schneider: Circadian genes regulate phagocytosis in Drosophila melanogaster.  In Preparation  

2. M. Shirasu-Hiza, D.S. Schneider: (2007) Confronting physiology: how do infected flies die?.  Cellular Microbiology  9(12): 2775-2783

3. D.S. Schneider, J. Ayres, S. Brandt, A. Costa, M. Dionne, M. Gordon, E. Mabery, M. Moule, L. Pham, and M. Shirasu-Hiza: (2007) Drosophila eiger mutants are sensitive to extracellular pathogens.  PLoS Pathogens  3(3): e41

4. L. Pham, M. Dionne, M. Shirasu-Hiza, and D.S. Schneider: (2007) A specific primed immune response in Drosophila is dependent on phagocytes.  PLos Pathogens  3(3): e26

5. M. Shirasu-Hiza, M. Dionne, L. Pham, J. Ayres, and D.S. Schneider: (2007) Circadian rhythm and innate immunity in Drosophila melanogaster.  Current Biology  17(10): R353-355

6. M. Dionne, L. Pham, M. Shirasu-Hiza, and D.S. Schneider: (2006) Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila.  Current Biology  16(20): 1977-1985

URL for lab page:
 

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