Mimi
Shirasu-Hiza
Our laboratory aims to understand how specific circadian-regulated physiological functions (such as innate immunity, metabolism, and sleep) contribute to health and disease 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. Moreover, many diseases (bacterial infeciton, Alzheimer's, Parkinson's, Huntington's, bipolar disease, schizophrenia, epilepsy, breast cancer, aging) are associated with loss of circadian regulation. How does loss of circadian regulation accelerate or delay the progression of disease? We 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. We now have three major foci for our research: innate immune cell function; metabolism; and sleep. 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 disease pathology.
- Hill VM, O’Connor RM, Sissoko GB, Irobunda IS, Leong S, Canman JC, Shirasu-Hiza M. A bi-directional relationship between sleep and oxidative stress in Drosophila. PLoS Biology (accepted).
- O'Connor RM, Stone EF, Wayne CR, Marcinkevicius EV, Ulgherait M, Delventhal R, Pantalia MM, Hill VM, Zhou CG, McAllister S, Chen A, Ziegenfuss JS, Grueber WB, Canman JC, Shirasu-Hiza MM.A Drosophila model of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells. J Cell Biol 2017 Mar 6;216(3):595-605. doi: 10.1083/jcb.201607093. Epub 2017 Feb 21.
• Highlighted in J Cell Biol: Logan M. Fragile phagocytes: FMRP positively regulates engulfment activity. J Cell Biol 2017 Feb 22. doi: 10.1083/jcb.201702034
• Selected as Editors’ Choice in Science Signaling: Mushegian A. Impaired phagocytosis in fragile X. Sci Signal. 2017 Apr 4; 10 (473). Doi: 10.1126/scisignal.aan3520
- Ulgherait M, Chen A, Oliva MK, Kim HX, Canman JC, Ja WW, Shirasu-Hiza M. Dietary restriction extends the lifespan of circadian mutants tim and per. Cell Metabolism2016 Dec 13;24(6):763-764. doi: 10.1016/j.cmet.2016.11.002.
- Allen VW, O’Connor RM, Ulgherait M, Zhou CG, Stone EF, Hill VM, Murphy KR, Canman JC, Ja WW, Shirasu-Hiza MM. period-regulated feeding behavior and TOR signaling modulate survival of infection. Current Biology 2015 Dec 29. pii: S0960-9822(15)01490-6.
- Stone EF, Fulton BO, Ayres JS, Pham LN, Ziauddin J, Shirasu-Hiza MM. The circadian clock protein Timeless regulates phagocytosis of bacteria in Drosophila. PLoS PathogensJan;8(1):e1002445.
• Highlighted in Nature Rev Microbiol 2012 Feb 13;10(3):162.