Mimi Shirasu-Hiza, PhD

Departments And Divisions

  • Department of Genetics & Development
  • Assistant Professor of Genetics & Development
Mimi Shirasu-Hiza, <span>PhD</span>

Our laboratory studies neuroimmune communication in Drosophila melanogaster.  Clock neurons regulate the oscillation of biological functions over the 24 hour day, including complex physiologies of the immune system.  The molecular mechanisms underlying the transmission of information from neurons to peripheral immune cells remain unknown.  Using quantitative live fluorescence imaging and molecular genetics, we are mapping the specific neurotransmitters and signaling pathways that mediate circadian neuroimmune communication.  In addition, many neuronal disease states, including autism, Alzheimer’s, Parkinson’s, and even aging, lead to both loss of circadian rhythm and misregulation of the immune system.  We are investigating whether the effects of neuronal disease on immunity are mediated by circadian clock neuronal function.

Circadian-regulated immunity: how does your circadian clock help you fight infection?

    Education & Training

  • BS, Molecular Biophysics and Biochemistry, Yale University
  • PhD, Biochemistry and Cell Biology, Univ. of California, San Francisco
  • Fellowship: Stanford University School of Medicine

Lab Locations

  • Hammer Health Sciences Building

    701 West 168th Street
    Rm 1604
    New York, NY 10032
    Phone:
    (212) 305-4186
    Email:
    ms4095@cumc.columbia.edu

Honors & Awards

2011 March of Dimes, Basil O'Connor Award

2012 Hirschl Career Award

Research Interests

  • Neurobiology of Learning and Memory
  • Neurogenetics
  • Neural Degeneration and Repair
  • Cellular/Molecular/Developmental Neuroscience

Grants

2011 March of Dimes, Basil O'Connor Award

2012 Hirschl Career Award

Lab Projects

  • 1) Neuroimmunity:  How does the brain regulate immunity against infection?  16 neurons in the fly brain are master regulators of circadian rhythm.  We are dissecting the molecular pathway from those 16 neurons to peripheral immune cells, working our way from each end by: 

    a) Defining the neuronal circuits that control circadian immunity

    b) Identifying the cell biological mechanisms of immune cells that are circadian-regulated.

  • 2) Novel circadian-regulated immune mechanisms:  What non-immune system physiologies significantly affect survival of infection?  Why are we more vulnerable to infection when we are tired, depressed, or diabetic?  Resistance mechanisms, or mechanisms of the immune system, affect microbial growth.  In contrast, tolerance mechanisms affect the organism's ability to tolerate the pathogenic effects of infection.  We are identifying tolerance mechanisms associated with:

    a) Sleep--why we sleep remains largely mysterious.  Does sleep affect immunity against infection and how?  We are using new sleep mutants and pharmacological manipulations to probe this relationship.

    b)  Metabolism--we found that the acute flux of dietary nutrients affects immunity against specific types of infection and are identifying the specific metabolic pathways involved.

  • 3) Neurological disease and immunity:  Many neurological disease states, including autism, Alzheimer’s, Parkinson’s, and even aging, lead to both loss of circadian rhythm and misregulation of the immune system.  Loss of circadian regulation by genetic or environmental manipulation leads to changes in immunity.  Does loss of circadian regulation due to neurological disease also change immunity?  And does this immune dysfunction contribute to progression of neurological disease?  Drosophila provides an excellent model system for studying many neurological diseases.  We are currently focused on three models:

    a) Aging

    b) Fragile X syndrome (a major cause of autism in humans)

    c) Parkinson's

Lab Members

  • Elizabeth Stone, graduate student (Neuroscience, MD/PhD)
  • Victoria Allen, graduate student (Integrated Program)
  • Vanessa Hill, graduate student (Integrated Program)
  • Emily Marcinkevicius, postdoctoral fellow
  • Reed O'Connor, technician

Publications

-  E. Stone, B. Fulton, J. Ayres, L. Pham, J. Ziauddin, and M. Shirasu-Hiza.  The circadian clock protein Timeless regulates phagocytosis of bacteria in Drosophila.  PLoS Pathogens (2012) Jan;8(1):e1002445.  doi: 10.1371/journal.ppat.1002445.

            •  Highlighted in Nat Rev Microbiol. 2012 Mar; 10(3):162.

-  Sait M, Kamneva O, Fay D, Kirienko N, Polek J, Shirasu-hiza M and Ward NL (2011) Genomic and experimental evidence suggests that Verrucomicrobium spinosum interacts with eukaryotes. Front. Microbio. 2:211. doi:10.3389/fmicb.2011.00211.

-  M. Shirasu-Hiza and D.S. Schneider.  Confronting physiology: how do infected flies die? Cell Microbiol.  2007 Dec;9(12):2775-83.

-  M. Shirasu-Hiza, M. Dionne, L. Pham, J. Ayres, and D.S. Schneider.  Interactions between circadian rhythm and innate immunity in Drosophila melanogaster. Curr Biol. 2007 May 15;17(10):R353-5.

            •  Described in Research Highlights, Nature 447, 356-357 (24 May 2007)

-  D.S. Schneider, J.S. Ayres, S. Brandt, A. Costa, M. Dionne, M. Gordon, E. Mabery, M. Moule, L. Pham, and M. Shirasu-Hiza.  Drosophila eiger mutants are sensitive to extracellular pathogens. PLoS Pathogens, 2007 Mar 23; 3(3): e41.

-  L. Pham, M. Dionne, M. Shirasu-Hiza, and D.S. Schneider.   A specific primed immune response in Drosophila is dependent on phagocytes.  PLoS Pathogens, 2007 Mar 9; 3(3):e2.

-  M. Dionne, L. Pham, M. Shirasu-Hiza, and D.S. Schneider.  foxo links wasting and disease resistance in Mycobacterium-infected Drosophila.  Curr Biol. 16(20): 1977-85 (2006).

For a complete list of publications, please visit PubMed.gov