Mimi Shirasu-Hiza, PhD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Genetics & Development

Our laboratory aims to understand how specific circadian-regulated physiological functions 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.

Gender

  • Female

Credentials & Experience

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

Honors & Awards

2011 March of Dimes, Basil O'Connor Award

2012 Hirschl Career Award

2016 The Harold and Golden Lamport Award for Excellence in Basic Science Research, CUMC

Research

Circadian-regulated physiological functions: how does your circadian clock help you fight disease?

Our laboratory aims to understand how specific circadian-regulated physiological functions 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.

Research Interests

  • Neurobiology of Learning and Memory
  • Neurogenetics
  • Neural Degeneration and Repair
  • Cellular/Molecular/Developmental Neuroscience
  • Circadian-regulated metabolism
  • glial development and pathology
  • Sleep
  • mitochondria biology and disease

Grants

2011 March of Dimes, Basil O'Connor Award

2012 Hirschl Career Award

2013 NIH R01 GM105775

2013 NIH R01 AG045842

CHARLES REVSON SENIOR FELLOWSHIP (Private)

Jul 1 2017 - Jun 30 2019

AGING OF TISSUE-SPECIFIC CLOCKS IN THE IMMUNE SYSTEM OF DROSOPHILA (Federal Gov)

Aug 15 2013 - May 31 2018

CIRCADIAN REGULATION OF PHAGOCYTOSIS (Federal Gov)

May 1 2013 - Jan 31 2018

INVESTIGATING NOVEL MECHANISMS OF HOST TOLERANCE OF P. AERUGINOSA AND B. CEPACIA INFECTION (Private)

Jul 1 2012 - Jun 30 2017

PHAGOCYTOSIS IS MISREGULATED IN A DROSOPHILA MODEL OF FRAGILE X SYNDROME (Federal Gov)

Sep 1 2013 - Aug 31 2015

INVESTIGATING CIRCADIAN-REGULATED IMMUNE RESPONSES IN DFMR1 (Private)

Feb 1 2011 - Sep 30 2013

Selected Publications

-  Y. Zhuravlev, S. Hirsch, S.N. Jordan, M. Shirasu-Hiza, J. Dumont, and J.C. Canman. 2017. CYK-4 regulates Rac, not Rho, during cytokinesis. Molecular Biology of the Cell (in press).

-  O'Connor R.M., Stone E.F., Wayne C.R., Marcinkevicius E.V., 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

-  Sundaramoorthy S, Garcia Badaracco A, Hirsch SM, Park JH, Davies T, Dumont J, Shirasu-Hiza M, Kummel AC, Canman JC.Low efficiency Upconversion Nanoparticles for High-Resolution Coalignment of Near-Infrared and Visible Light Paths on a Light Microscope. . 2017 Feb 21. doi: 10.1021/acsami.6b15322.

-  Davies T, Sundaramoorthy S, Jordan SN, Shirasu-Hiza M, Dumont J, Canman JC.Using fast-acting temperature-sensitive mutants to study cell division on Caenorhabditis elegans..2017;137:283-306. doi: 10.1016/bs.mcb.2016.05.004.

-  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 perCell Metabolism 2016 Dec 13;24(6):763-764. doi: 10.1016/j.cmet.2016.11.002.

-  Jordan SN, Davies T, Dumont J, Shirasu-Hiza M, Canman JC. Cortical PAR polarity proteins promote robust cytokinesis during asymmetric cell division. Journal of Cell Biology 2016 Jan 4;212(1):39-49.

-  Allen VW, O’Connor RM, Ulgherait M, Zhou CG, Stone EF, Hill VM, Murphy KR, Canman JC, Ja WW, Shirasu-Hiza MMperiod-regulated feeding behavior and TOR signaling modulate survival of infection. Current Biology 2015 Dec 29. pii: S0960-9822(15)01490-6.

-  Amaral FE, Parker D, Randis TM, Kulkarni R, Prince AS, Shirasu-Hiza MM, Ratner AJ. Rheostat Control of S. pneumoniae Virulence by Minimal Manipulation of pneumolysin mRNA Folding Free Energy. PLoS One 2015 Mar 23;10(3):e0119823.

-  Davies T, Jordan SN, Chand V, Sees JA, Laband K, Carvalho AX, Shirasu-Hiza M, Kovar DR, Dumont J, Canman JC. High-resolution temporal analysis reveals a functional timeline for the molecular regulation of cytokinesis. Developmental Cell 2014 Jul 28;30(2):209-23.

-  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 Pathogens Jan;8(1):e1002445.

            • Highlighted in Nature Rev Microbiol 2012 Feb 13;10(3):162.

-  Sait M, Kamneva OK, Fay DS, Kirienko NV, Polek J, Shirasu-Hiza MM, Ward NL. Genomic and experimental evidence suggests that Verrucomicrobium spinosum interacts with eukaryotes. Frontiers in Microbiology. 2011 Oct 18;2:211.

-  Shirasu-Hiza MM, Dionne MS, Pham LN, Ayres JS, Schneider DS.  Interactions between circadian rhythm and innate immunity in Drosophila melanogaster. Current Biology 2007 May 15;17(10):R353-5.

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

-  Schneider DS, Ayres JS, Brandt SM, Costa A, Dionne MS, Gordon MD, Mabery EM, Moule MG, Pham LN, Shirasu-Hiza MM. Drosophila eiger mutants are sensitive to extracellular pathogens. PLoS Pathogens 2007 Mar; 3(3): e41.

-  Pham LN, Dionne MS, Shirasu-Hiza M, Schneider DS. A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathogens, 2007 Mar; 3(3):e2

-  Dionne MS, Pham LN, Shirasu-Hiza M, Schneider DS. Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila. Current Biology

-  Mitchison TJ, Maddox P, Gaetz J, Groen A, Shirasu M, Desai A, Salmon ED, Kapoor TM.Roles of polymerization dynamics, opposed motors, and a tensile element in governing the length of Xenopus egg extract spindles. Molecular Biology of the Cell 2005 Jun; 16(6): 3064-76.Epub 2005 Mar 23.

-  Shirasu-Hiza M, Perlman ZE, Wittmann T, Karsenti E, Mitchison TJ. Eg5 causes elongation of meiotic spindles when flux-associated microtubule depolymerization is blocked. Current Biology 2004 Nov 9; 14(21): 1941-5.

-  Shirasu-Hiza M, Coughlin P, Mitchison TJ. Identification of XMAP215 as a Microtubule Destabilizing Factor in Xenopus Egg Extract by Biochemical Purification. Journal of Cell Biology 2003 Apr 28;161(2):349-58.