Michal Šmída

Functional Genomics

Tumors have Achilles´ heel too! Just to find it!

  • Mission: Describe resistance mechanisms of leukemias to current therapies and identify novel molecular targets of therapy.
  • Vision: Propose innovative therapeutic opportunities with superior efficacy.

We are aiming at identification of novel drug targets that might be exploited in the clinic as innovative targeted therapies, with the focus on two common hematologic malignancies, chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). CRISPR/Cas9 technology along with lentiviral infection is used to generate cell models carrying common mutations observed in the patients. Functional consequences of these aberrations onto cell signaling and behavior are thoroughly analyzed. 

SELECTED PUBLICATIONS
  • Ledererova A, Dostalova L, Kozlova V, Peschelova H, Ladungova A, Culen M, Loja T, Verner J, Pospisilova S, Smida M*, Mancikova V* (*shared authors). Hypermethylation of CD19 promoter enables antigen-negative escape to CART-19 in vivo and in vitro. J ImmunoTher Cancer. 2021 Aug;9(8):e002352. DOI: 10.1136/jitc-2021-002352
  • Kozlova V, Ledererova A, Ladungova A, Janovska P, Slusarczyk A, Domagala J, Kopcil P, Vakulova V, Oppelt J, Bryja V, Doubek M, Mayer J, Pospisilova S, Smida M. CD20 is dispensable for B-cell receptor signaling but is required for proper actin polymerization, adhesion and migration of malignant B cells. Plos One. 2020 Mar 25;15(3):e0229170. DOI: 10.1371/journal.pone.0229170
  • Mancikova V, Peschelova H, Kozlova V, Ledererova A, Ladungova A, Verner J, Loja T, Mayer J, Pospisilova S, Smida M. Performance of a-CD19 Chimeric Antigen Receptor T cells in genetically defined classes of Chronic Lymphocytic Leukemia. J ImmunoTher Cancer. 2020 Mar;8(1):e000471. DOI: 10.1136/jitc-2019-000471
  • Smida M, Fece de la Cruz F, Uras IZ, van Jaarsveld R, Konopka T, Nagy-Bojarszky K, Muellner MK, Bago-Horvath Z, Haura EB, Loizou JI, Nijman SMB. MEK inhibitors block growth of Ataxia Telangiectasia Mutated (ATM) mutant lung tumors. Nature Communications. 2016;7, 13701. DOI: 10.1038/ncomms13701
SPECIALIZED EXPERTISE AND TECHNOLOGY

CRISPR/Cas9 technology, production of knockout and knock-in cell lines

Genome-wide CRISPR/Cas9 knockout screening

Drug screening using diverse drug libraries on primary cells

Portfolio of cell biology methods, incl. lentiviral infection

Genomic approaches like RNA sequencing, ATACseq, single-cell RNA sequencing

CAR-T cell technology

COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES

Czech National Infrastructure for Biological Data ELIXIR CZ

National infrastructure for translational medicine EATRIS-CZ