Our Faculty

Akira Imamoto, DDS PhD

  • Associate Professor of Ben May Department of Cancer Research
    Committee on Cancer Biology
  • Research and Scholarly Interests: Cardiovascular Diseases, DiGeorge Syndrome, Network, Gene, Pharyngeal Arches, Signal Transduction Pathways, Velocardiofacial Syndrome
  • Websites: BenMay, Research Network Profile
  • Contact: aimamoto@uchicago.edu
  • Graduate Program: Cancer Biology

We are interested in elucidating mechanisms by which a mutation or combination of mutations affect broader network within and between cells during development. Our current model is DiGeorge/velocardiofacial/del22q11 syndrome (OMIM: 188400 and 192430), a contiguous gene syndrome in approximately 1 in 4000 live births. The common manifestations of this syndrome include cardiovascular defects, aplasia or hypoplasia of the thymus and parathyroid glands, and craniofacial anomalies. Urogenital defects, learning disabilities, and other psychiatric disorders are also common. Two 22q11 genes, TBX1 and CRKL, have been implicated in this syndrome. While they show a strong dosage-sensitive interaction in mouse models, they encode different classes of proteins. Tbx1 is a T-box transcription factor, while CRKL is an adapter protein presumably down stream of tyrosine kinases. To date, few direct links have been known between the signaling pathways in which they are involved. Using multitudes of techniques, we aim to find missing pieces to establish their functional links.

Fred Hutchinson Cancer Res Ctr
Seattle, WA
Post-doc
1996

Osaka University
Osaka, Japan
PhD
1988

Osaka University
Osaka, Japan
DDS
1984

Cell shape-based chemical screening reveals an epigenetic network mediated by focal adhesions.
Kanazawa T, Michida H, Uchino Y, Ishihara A, Zhang S, Tabata S, Suzuki Y, Imamoto A, Okada M. Cell shape-based chemical screening reveals an epigenetic network mediated by focal adhesions. FEBS J. 2021 10; 288(19):5613-5628.
PMID: 33768715

Essential role of the Crk family-dosage in DiGeorge-like anomaly and metabolic homeostasis.
Imamoto A, Ki S, Li L, Iwamoto K, Maruthamuthu V, Devany J, Lu O, Kanazawa T, Zhang S, Yamada T, Hirayama A, Fukuda S, Suzuki Y, Okada M. Essential role of the Crk family-dosage in DiGeorge-like anomaly and metabolic homeostasis. Life Sci Alliance. 2020 02; 3(2).
PMID: 32041892

Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive regulator of genitourinary development.
Haller M, Mo Q, Imamoto A, Lamb DJ. Murine model indicates 22q11.2 signaling adaptor CRKL is a dosage-sensitive regulator of genitourinary development. Proc Natl Acad Sci U S A. 2017 05 09; 114(19):4981-4986.
PMID: 28439006

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.
Lopez-Rivera E, Liu YP, Verbitsky M, Anderson BR, Capone VP, Otto EA, Yan Z, Mitrotti A, Martino J, Steers NJ, Fasel DA, Vukojevic K, Deng R, Racedo SE, Liu Q, Werth M, Westland R, Vivante A, Makar GS, Bodria M, Sampson MG, Gillies CE, Vega-Warner V, Maiorana M, Petrey DS, Honig B, Lozanovski VJ, Salomon R, Heidet L, Carpentier W, Gaillard D, Carrea A, Gesualdo L, Cusi D, Izzi C, Scolari F, van Wijk JA, Arapovic A, Saraga-Babic M, Saraga M, Kunac N, Samii A, McDonald-McGinn DM, Crowley TB, Zackai EH, Drozdz D, Miklaszewska M, Tkaczyk M, Sikora P, Szczepanska M, Mizerska-Wasiak M, Krzemien G, Szmigielska A, Zaniew M, Darlow JM, Puri P, Barton D, Casolari E, Furth SL, Warady BA, Gucev Z, Hakonarson H, Flogelova H, Tasic V, Latos-Bielenska A, Materna-Kiryluk A, Allegri L, Wong CS, Drummond IA, D'Agati V, Imamoto A, Barasch JM, Hildebrandt F, Kiryluk K, Lifton RP, Morrow BE, Jeanpierre C, Papaioannou VE, Ghiggeri GM, Gharavi AG, Katsanis N, Sanna-Cherchi S. Genetic Drivers of Kidney Defects in the DiGeorge Syndrome. N Engl J Med. 2017 02 23; 376(8):742-754.
PMID: 28121514

A pre-metazoan origin of the CRK gene family and co-opted signaling network.
Shigeno-Nakazawa Y, Kasai T, Ki S, Kostyanovskaya E, Pawlak J, Yamagishi J, Okimoto N, Taiji M, Okada M, Westbrook J, Satta Y, Kigawa T, Imamoto A. A pre-metazoan origin of the CRK gene family and co-opted signaling network. Sci Rep. 2016 Sep 30; 6:34349.
PMID: 27686861

RKIP regulates MAP kinase signaling in cells with defective B-Raf activity.
Zeng L, Ehrenreiter K, Menon J, Menard R, Kern F, Nakazawa Y, Bevilacqua E, Imamoto A, Baccarini M, Rosner MR. RKIP regulates MAP kinase signaling in cells with defective B-Raf activity. Cell Signal. 2013 May; 25(5):1156-65.
PMID: 23416466

A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors.
Seo JH, Wood LJ, Agarwal A, O'Hare T, Elsea CR, Griswold IJ, Deininger MW, Imamoto A, Druker BJ. A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors. Cancer Res. 2010 Sep 15; 70(18):7325-35.
PMID: 20807813

Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration.
Shemon AN, Eves EM, Clark MC, Heil G, Granovsky A, Zeng L, Imamoto A, Koide S, Rosner MR. Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration. PLoS One. 2009 Jun 24; 4(6):e6028.
PMID: 19551145

Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop.
Seo JH, Suenaga A, Hatakeyama M, Taiji M, Imamoto A. Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop. Mol Cell Biol. 2009 Jun; 29(11):3076-87.
PMID: 19307307

Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target.
Zeng L, Imamoto A, Rosner MR. Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert Opin Ther Targets. 2008 Oct; 12(10):1275-87.
PMID: 18781826

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