Historically, centrosomes have been known to be essential for cilia formation and accurate cell division. At their core, centrosomes are composed of a pair of centrioles surrounded by an amorphous Peri-Centriolar Material (PCM) formed by various multi-protein complexes.
The centriole templates cilia formation during interphase, while the PCM assembles spindle poles during mitosis to nucleate astral and spindle microtubules (MT asters). Thus, centrosomes are critical for animal development and their dysfunction results in many developmental disorders.
In addition, nearly all types of cancer cells have abnormal numbers of centrosomes and the abnormal number of centrosomes has a direct correlation to chromosomal instability during tumor formation.
This implicates that not only the functionality but also the correct number of centrosomes is crucial for the viability of organisms. Thus, it is very important for biology and medical science to understand the regulatory mechanisms of centrosome biogenesis.
To this end, we aim to elucidate the fundamental principles of centrosome biogenesis to uncover how their dysfunctions can lead to developmental disorders, genomic instability, cancer and diseases associated with aging.
Currently, our studies are concentrated in the following topics using an ideal model organism, fruit fly. We develop a robust system using fruit fly where genetic and biochemical strategies are applied together to study centrosome biogenesis both in vivo and in vitro.
Brenke JK, Salmina ES, Ringelstetter L, Dornauer S, Kuzikov M, Rothenaigner I, Schorpp K, Giehler F, Gopalakrishnan J, Kieser A, Gul S, Tetko IV, and Hadian K (2016). Identification of small-molecule frequent hitters of glutathione s-transferase-glutathione interaction. J Biomol Screen 10.1177/1087057116639992.
Gabriel E, Wason A, Ramani A, Gooi LM, Keller P, Pozniakovsky A, Poser I, Noack F, Telugu NS, Calegari F, Saric T, Hescheler J, Hyman AA, Gottardo M, Callaini G, Alkuraya FS, and Gopalakrishnan J (2016). Cpap promotes timely cilium disassembly to maintain neural progenitor pool. EMBO J 35, 803-819.
Thomopoulou P, Sachs J, Teusch N, Mariappan A, Gopalakrishnan J, and Schmalz HG (2016). New colchicine-derived triazoles and their influence on cytotoxicity and microtubule morphology. ACS Med Chem Lett 7, 188-191.
Pannu V, Rida PC, Celik B, Turaga RC, Ogden A, Cantuaria G, Gopalakrishnan J, and Aneja R (2014). Centrosome-declustering drugs mediate a two-pronged attack on interphase and mitosis in supercentrosomal cancer cells. Cell death & disease 5, e1538.
Schorpp K, Rothenaigner I, Salmina E, Reinshagen J, Low T, Brenke JK, Gopalakrishnan J, Tetko IV, Gul S, and Hadian K (2014). Identification of small-molecule frequent hitters from alphascreen high-throughput screens. J Biomol Screen 19, 715-726.
Zheng X, Gooi LM, Wason A, Gabriel E, Mehrjardi NZ, Yang Q, Zhang X, Debec A, Basiri ML, Avidor-Reiss T, Pozniakovsky A, Poser I, Saric T, Hyman AA, Li H, and Gopalakrishnan J (2014). Conserved tcp domain of sas-4/cpap is essential for pericentriolar material tethering during centrosome biogenesis. Proc Natl Acad Sci U S A 111, E354-363.
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assoc.RG (since 08/2018) Principal Investigator - CMMC-JRG IX (11/2012-07/2018)show more…