Castellano Lab

Non-coding RNA in cancer lab

Dr Castellano's group focuses on a class of molecules called noncoding RNA (ncRNA). 2% of human DNA contains RNA that encodes proteins, whilst the vast majority of the rest represent ncRNA. We, and others, have shown several RNAs from this class are pivotal in the development of cancer. Our particular focus is on microRNAs and long ncRNAs. They were thought to have no function so there is still much to be learnt about their roles in cancerogenesis. We hope to identify ncRNAs and novel pathways involved in cancer growth or treatment resistance that could be targeted with new therapies. The modulation of these molecules is possible in clinical practice and early drug trials targeting specific ncRNA are underway. We also suspect that these molecules will make good biomarkers as they are very stable in the blood and could be used to assist in earlier diagnosis and monitoring treatment response.

Selected publications

• Circulating MicroRNAs in Small-bowel Neuroendocrine Tumors: A Potential Tool for Diagnosis and Assessment of Effectiveness of Surgical Resection.
  Malczewska A, Frampton AE, Mato Prado M, Ameri S, Dabrowska AF, Zagorac S, Clift AK, Kos-Kudła B, Faiz O, Stebbing J, Castellano L, Frilling A.
  1 Jul 2021 Annals of surgery 274(1).
• SCIRT lncRNA Restrains Tumorigenesis by Opposing Transcriptional Programs of Tumor-Initiating Cells.
  Zagorac S, de Giorgio A, Dabrowska A, Kalisz M, Casas-Vila N, Cathcart P, Yiu A, Ottaviani S, Degani N, Lombardo Y, Tweedie A, Nissan T, Vance KW, Ulitsky I, Stebbing J, Castellano L.
  1 Feb 2021 Cancer Research 81(3):580-593.
• TGF-β induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression.
  Ottaviani S, Stebbing J, Frampton AE, Zagorac S, Krell J, De Giorgio A, Trabulo SM, Nguyen VTM, Magnani L, Feng H, Giovannetti E, Funel N, Gress TM, Jiao LR, Lombardo Y, Lemoine NR, Heeschen C, Castellano L.
  1 Dec 2018 Nature Communications 9(1).
• Sustained expression of miR-26a promotes chromosomal instability and tumorigenesis through regulation of CHFR.
  Castellano L, Dabrowska A, Pellegrino L, Ottaviani S, Cathcart P, Frampton AE, Krell J, Stebbing J.
  1 Jan 2017 Nucleic Acids Research 45(8):4401-4412.
• MIR-515-5p controls cancer cell migration through MARK4 regulation.
  Pardo OE, Castellano L, Munro CE, Hu Y, Mauri F, Krell J, Lara R, Pinho FG, Choudhury T, Frampton AE, Pellegrino L, Pshezhetskiy D, Wang Y, Waxman J, Seckl MJ, Stebbing J.
  1 Apr 2016 EMBO Reports 17(4):570-584.
• TP53 regulates miRNA association with AGO2 to remodel the miRNA-mRNA interaction network.
  Krell J, Stebbing J, Carissimi C, Dabrowska AF, Giorgio AD, Frampton AE, Harding V, Fulci V, Macino G, Colombo T, Castellano L.
  1 Mar 2016 Genome Research 26(3):331-341.
• MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promote pancreatic tumor growth and progression.
  Frampton AE, Castellano L, Colombo T, Giovannetti E, Krell J, Jacob J, Pellegrino L, Roca-Alonso L, Funel N, Gall TMH, De Giorgio A, Pinho FG, Fulci V, Britton DJ, Ahmad R, Habib NA, Coombes RC, Harding V, Knösel T, Stebbing J, Jiao LR.
  1 Jan 2014 Gastroenterology146 (1).

---

Job Opportunities

People interested in postgraduate or postdoctoral positions should contact directly Dr Leandro Castellano L.Castellano@sussex.ac.uk