Professor Dot Bennett Group Page

Bennett-Sviderskaya Laboratory

Dorothy C Bennett, Professor of Cell Biology	Elena V Sviderskaya Senior Lecturer

Cell Biology Research Centre, Molecular and Clinical Sciences Research Institute, Jenner Wing (Mailpoint J2A) St George's, University of London Cranmer Terrace London SW17 0RE, UK	Cell Biology Research Centre, Molecular and Clinical Sciences Research Institute, Jenner Wing (Mailpoint J2A) St George's, University of London Cranmer Terrace London SW17 0RE, UK
dbennett@sgul.ac.uk	esviders@sgul.ac.uk

Looking for our cell lines? - See Wellcome Trust Functional Genomics Cell Bank

Looking for cell culture methods? See Materials and Methods used in melanocyte culture

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Current group members:

Dr Robert Brooks (Hon. Senior Lecturer)

Mr Philip Goff (Research Assistant/PhD Student)

Miss Emily Woodcock (PhD Student)

Dr Shyamal Amin (Academic Visitor)

Mr Muhammad Akbar (Project Student)

Miss Zahida Faisal (Project Student)

Our research interests:

The melanocyte, or pigment cell. (Available in a range of pleasing, natural colours, including gold if you count fish.)

Its cancer - malignant melanoma. (Not pleasing; a common, highly malignant and rapidly progressing disease.) Molecular genetics of melanoma.
The role of cell senescence and immortalization in melanoma development and therapy, and in ageing.
Cell senescence and wound healing: possible therapeutic applications.
Genetics of melanocytes. Pigmentation is an attractive and accessible system for genetic study; for example over 350 genetic loci required for normal pigmentation are known in the mouse. The molecular, cellular and genetic basis of pigmentary defects, like vitiligo and Hermansky-Pudlak syndrome.
Development of melanocytes. Characterization of the developmental precursors of melanocytes: melanoblasts and stem cells. Analysis and control of gene expression during differentiation.

Current research topics:

Melanocyte senescence and immortalization: relations to genetics and progression in cutaneous malignant melanoma
The therapeutic potential of cell senescence pathways
Molecular genetics of pigmentation in mice and humans
Control of differentiation and determination of immortal mouse neural crest-like stem cell lines

The Wellcome Trust Functional Genomics Cell Bank :

Our research group maintains the Wellcome Trust Functional Genomics Cell Bank, Director Dr Elena Sviderskaya.

The bank holds over 250 immortal lines of mammalian cells of various types, including:

over 120 lines of mouse melanocytes, mostly carrying mutations at various pigmentary loci;
7 lines of mouse melanoblasts, and
around 40 lines of human melanoma cells from various stages of melanoma progression.
4 lines/10 sublines of immortalized normal human melanocytes

Many of these are freely available to researchers on request, with some restrictions on unpublished lines and lines obtained from other laboratories.

Most frequently requested line:

melan-a a/a (nonagouti, black) mouse melanocytes, from C57BL/6 mice.

Recent group publications:

Original Papers

Patel S, Wilkinson CJ and Sviderskaya EV. (2020) Loss of both CDKN2A and CDKN2B allows for centrosome overduplication in melanoma. J Invest Dermatol. In press.

Zhang Y, Takahashi Y, Hong HP, Liu F, Bednarska J, Goff PS, Novak P, Shevchuk A, Gopal S, Barozzi IG, Magnani L, Sakai H, Suguru Y, Fujii T, Erofeev A, Gorelkin P, Majouga A, Weiss DJ, Edwards C, Ivanov A, Klenerman D, Sviderskaya EV*, Edel JB and Korchev YE (2019) High-resolution label-free 3D mapping of extracellular pH of living cells. Nature Comms 10:5610.

Sanzà P, Evans RD, Briggs DA, Cantero M, Montoliu L, Patel S, Sviderskaya EV, Itzen A, Figueiredo AC, Seabra MC and Hume AN (2019) Nucleotide exchange factor Rab3GEP facilitates, but is not the sole determinant of, the specificity of Rab27a targeting. J Cell Sci 2019. jcs.212035.

Zhang Z, Gong J, Sviderskaya EV, Wei A and Li W (2019) Mitochondrial NCKX5 regulates melanosomal biogenesis and pigment production J Cell Sci 132, pii: jcs232009.

Hernando B, Swope VP, Guard S, Starner RJ, Choi K, Anwar A, Cassidy P, Leachman S, Kadekaro AL, Bennett DC and Abdel-Malek ZA (2019) In vitro behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants. Pigm Cell Melanoma Res 32, 259-268.

Norton EJ, Bridges LR, Kenyon LC, Esiri MM, Bennett DC and Hainsworth AH (2019) Cell senescence and cerebral small vessel disease in the brains of people aged 80 years and older . J Neuropathol Exp Neurol 78 , 1066-1072.

Kohli JS, Tolomio E, Frigerio S, Maurichi A, Rodolfo M and Bennett DC (2017) Common delayed senescence of melanocytes from multiple primary melanoma patients. J Inv Dermatol 137, 766-8.

Marathe HG, Watkins-Chow DE, Weider M, Hoffmann A, Mehta G, Trivedi A, Aras S, Basuroy T, Mehrotra A, Bennett DC , Wegner M, Pavan WJ and de la Serna IL (2017) BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation. Nucl Acids Res 45, 6442-58.

Cairney CJ, LS Godwin, AE Bilsland, S Burns, KH Stevenson, L McGarry, J Revie, JD Moore, CM Wiggins, RS Collinson, C Mudd, E Tsonou, M Sadaie, DC Bennett, M Narita, CJ Torrance and WN Keith (2017) A 'synthetic-sickness' screen for senescence re-engagement targets in mutant cancer backgrounds. PLOS Genet 13, e1006942.

Kohli JS, Mir H, Wasif A, Chong H, Akhras V, Kumar R, Nagore E and Bennett DC (2017) ETS1, nucleolar and non-nucleolar TERT expression in nevus to melanoma progression. Oncotarget 8 , 104408-17.

Zhang Y, Clausmeyer J, Babakinejad B, Lapez A, Ali T, Shevchuk A, Takahashi Y, Novak P, Edwards C, Lab M, Gopal S, Chiappini C, Anand U, Magnani L, Coombes C, Gorelik J, Matsue T, Schuhmann W, Klenerman D, Sviderskaya EV * and Korchev YE (2016) Spearhead nanometric field-effect transistor sensors for single-cell analysis. ACS Nano 10, 3214-3221.

Dennis MK, Delevoye C, Acosta-Ruiz A, Hurbain I, Romao M, Hesketh GG, Goff PS, Sviderskaya EV, Bennett DC, Luzio JP, Galli T, Owen DJ, Raposo G and Marks MS (2016) BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers. J Cell Biol 214, 293-308.

Goto Y, I Yajima, MY Kumasaka, N Ohgami, A Tanaka, T Tsuzuki, Y Inoue, S Fukushima, H Ihn, M Kyoya, H Ohashi, T Kawakami, DC Bennett and M Kato (2016) Transcription factor LSF (TFCP2) inhibits melanoma growth. Oncotarget 7, 2379-90.

Jin Y, G Andersen, D Yorgov, TM Ferrara, S Ben, KM Brownson, PJ Holland, SA Birlea, J Siebert, A Hartmann, A Lienert, RM Luiten, A Wolkerstorfer, JP Wietze van der Veen, N van Geel, J Lambert, DC Bennett, A Taïeb, K Ezzedine, EH Kemp, DJ Gawkrodger, AP Weetman, S Koks, E Prans, K Kingo, M Karelson, MR Wallace, WT McCormack, A Overbeck, S Moretti, R Colucci, M Picardo, NB Silverberg, M Olssen, Y Valle, I Korobko, M Böhm, H Lim, I Hamzavi, L Zhou, Q-S Mi, PR. Fain, SA Santorico and RA Spritz (2016) Enhanced genome-wide association studies of autoimmune vitiligo identify 23 novel loci and highlight key pathobiological pathways and causal regulatory variation. Nature Genet 48, 1418-24.

Cao J, Dai X, Wan L, Wang H, Zhang J, Goff PS, Sviderskaya EV, Xuan Z, Xu Z, Xu X, Hinds P, Flaherty KT, Faller DV, Goding CR, Wang Y, Wei W and Cui R (2015) The E3 ligase APC/CCdh1 promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth. Sci Signal 8(392):ra87.

Dennis MK, Mantegazza AR, Snir OL, Tenza D, Acosta-Ruiz A, Delevoye C, Zorger R, Sitaram A, de Jesus-Rojas W, Ravichandran K, Rux J, Sviderskaya EV, Bennett DC, Raposo G, Marks MS and Setty SR (2015) BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery. J Cell Biol 209, 563-577.

Sadaie M, C Dillon, M Narita, AR Young, CJ Cairney, LS Godwin, CJ Torrance, DC Bennett, WN Keith and M Narita (2015) Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition. Mol Biol Cell 26 2971-85.

Fufa TD, Harris ML, Watkins-Chow DE, Levy D, Gorkin DU, Gildea DE, Song L, Safi A, Crawford GE, Sviderskaya EV, Bennett DC, Mccallion AS, Loftus SK and Pavan WJ (2015) Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes . Hum Mol Genet 24, 5433-50.

Evans RD, Robinson C, Briggs DA, Tooth DJ, Ramalho JS, Montoliu L, Sviderskaya EV and Hume AN (2014) Myosin-Va and actin dynamics oppose microtubule based transport to drive organelle dispersion Current Biology 24:1743-1750.

Actis P, Tokar S, Clausmeyer J, Babakinejad B, Mikhaleva S, Cornut R, Takahashi Y, Córdoba LA, Novak P, Shevchuck A, Dougan JA, Kazarian SG, Gorelkin P, Erofeev AS, Yaminsky IV, Unwin PR, Schuhmann W, Klenerman D, RusakovDA, Sviderskaya EV and Korchev YE (2014) Electrochemical nanoprobes for single-cell analysis. ACS Nano 8 :875-884.

Redmond RW, Rajadurai A, Udayakumar D, Sviderskaya EV and Tsao H (2014) Melanocytes are selectively vulnerable to UVA-mediated bystander oxidative signaling . J Invest Dermatol 134:1083-1090.

Lam RYY, Lin Z-X, Sviderskaya EV and Cheng CHK (2014) Mechanistic studies of anti-hyperpigmentary compounds: elucidating their inhibitory and regulatory actions. Int J Mol Sci 15:14649-14668.

Lobos-Gonzalez L, Aguilarguzmán L, Fernandez JG, Muñoz N, Hossain M, Bieneck S, Silva V, Burzio V, Sviderskaya EV, Bennett DC, Leyton L and Quest AFG (2014) Caveolin-1 is a risk factor for post-surgery metastasis in preclinical melanoma models. Melanoma Res 24 , 108-119.

Falletta P, P Bagnato, M Bono, M Monticone, MV Schiaffino, DC Bennett, CR Goding, C Tacchetti and C Valetti (2014) Melanosome-autonomous regulation of size and number: The OA1 receptor sustains PMEL expression. Pigm Cell Melanoma Res 27, 565-579 .

Muinonen-Martin AJ, Q Zhang, W Faller, C Moyes, A Drummond, O Susanto, D Veltman, G Kalna, C Lindsay, DC Bennett, OJ Sansom, R Herd, R Jones, LM Machesky, MJO Wakelam, DA Knecht and RH Insall (2014) Melanoma cells make LPA gradients that drive their chemotactic dispersal and invasion. PLoS Biol 12 :e1001966. doi: 10.1371/journal.pbio.1001966.

Web publication

Bennett DC, Hayward NK, Nathan N, Orlic-Milacic M and Rizos H (2019) Diseases of cellular senescence . In: Reactome - a curated knowledgebase of biological pathways 69. DOI: 10.3180/R-HSA-9630747.1
https://reactome.org/PathwayBrowser/#/R-HSA-9630747

Reviews

Gorgoulis V, P Adams, A Alimonti, DC Bennett, O Bischof, C Bishop, J Campisi, M Collado, K Evangelou, G Ferbeyre, J Gil, E Hara, V Krizhanovsky, D Jurk, A Maier, M Narita, L Niedernhofer, JF Passos, PD Robbins, CA Schmitt, J Sedivy, K Vougas, T von Zglinicki, D Zhou, M Serrano and M Demaria (2019) Perspective. Cellular senescence: defining a path forward. Cell 179, 813-27.

Kohli JS and DC Bennett (2017). Molecular genetics of melanoma progression. In: eLS (Encyclopedia of Life Sciences). (John Wiley & Sons, Ltd, Chichester, UK).

DOI: 10.1002/9780470015902.a0027340.

Bennett DC (2016) Genetics of melanoma progression: the rise and fall of cell senescence. Pigm Cell Melanoma Res 29, 122-40.

Godwin LS, JT Castle, JS Kohli, PS Goff, CJ Cairney, WN Keith, EV Sviderskaya and DC Bennett (2014) Isolation, culture and transfection of melanocytes. Curr Protocols Cell Biol 63 , 1.8.1-1.8.20.

Selected earlier papers (most cited):

Lu M, Breyssens H, Salter V, Zhong S, Hu Y, Baer C, Ratnayaka I, Sullivan A, Brown NR, Endicott J, Knapp S, Kessler BM, Middleton MR, Siebold C, Jones EY, Sviderskaya EV, Cebon J, John T, Caballero OL, Goding CR and Lu X (2013) Restoring p53 function in human melanoma cells by Inhibiting MDM2 and Cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer Cell 23:618-633.

Jin Y, SA Birlea, PR Fain, K Gowan, SL Riccardi, PJ Holland, CM Mailloux, AJD Sufit, SM Hutton, A Amadi-Myers, DC Bennett, MR Wallace, WT McCormack, EH Kemp, DJ Gawkrodger, AP Weetman, M Picardo, G Leone, A Taïeb, T Jouary, K Ezzedine, N van Geel, J Lambert, A Overbeck and RA Spritz (2010). Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. New Engl J Med 362, 1686-1697.

Setty SRG, Tenza D, Sviderskaya EV, Bennett DC, Raposo G and Marks MS (2008) Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. Nature 454:1142-1146.

Ha L, Ichikawa T, Anver M, Dickins R, Lowe S, Sharpless NE, Krimpenfort P, DePinho RA, Bennett DC, Sviderskaya EV* and Merlino G (2007) ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence. Proc Natl Acad Sci USA 104:10968-10973.

Jin Y, CM Mailloux, K Gowan, SL Riccardi, G LaBerge, DC Bennett, PR Fain and RA Spritz (2007) NALP1 in vitiligo-associated multiple autoimmune disease. New Engl J Med 356, 1216-1225.

Bennett DC (2003) Human melanocyte senescence and melanoma susceptibility genes. Oncogene 22, 3063-3069.

Bennett DC and ML Lamoreux (2003) The color loci of mice - a genetic century. Pigment Cell Res 16, 333-344.

Sviderskaya EV, SP Hill, TJ Evans-Whipp, L Chin, SJ Orlow, DJ Easty, SC Cheong, D Beach, RA DePinho and DC Bennett (2002) p16Ink4a in melanocyte senescence and differentiation. J Natl Cancer Inst 94, 446-454.

Suzuki T, Li W, Zhang Q, Karim A, Novak EK, Sviderskaya EV, Hill SP, Bennett DC, Chin L, Levin AV, Nieuwenhuis K, Fong C-T, Castellan C., Miterski B, Swank RT and Spritz RA (2002) Hermansky-Pudlak syndrome is caused by mutations in HPS4 , the human homolog of the mouse light ear gene. Nature Genet 30:321-324.

Job vacancies

Sorry, no vacancies at present.

We are always interested to hear from bright and creative researchers who are thinking about applying for their own funding/ fellowships on topics related to ours, and need a host lab.