Principal Investigator

Giovanna Zinzalla

Affiliated to research

Principal Investigator

About me

PRINCIPAL INVESTIGATOR

AREAS OF EXPERTISE

Chemical Biology, Organic and Medicinal Chemistry, Biochemistry, Structural Biology, Biochemical and Biophysical Assays, Protein-Protein Interactions, Transcription Factors, Drug Discovery

BIOGRAPHY

Dr. Zinzalla obtained her first class honours Laurea in Chemistry (equivalent to MChem) from the University of Milan and carried out her PhD studies with Prof. Stefano Maiorana and Dr Clara Baldoli also at the University of Milan. Her research focused on developing new metal complex conjugates of Peptide Nucleic Acids (PNAs) as biosensors, and she investigated novel trace-less linkers for solid-phase synthesis of drug-like small molecules in collaboration with GlaxoSmithKline.

In 2004 she was awarded a Marie Curie EIF Individual Research Fellowship and appointed as Postdoctoral Research Assistant at the University of Cambridge with Professor Steven Ley, where she initiated a project focused on exploring the role of molecular diversity for drug discovery, with the design of natural product-like compounds as novel therapeutic agents.

In June 2006 she joined the School of Pharmacy, University College London (UCL) (London, UK) as a Senior Research Fellow funded by Cancer Research UK (CR UK), within the CR UK Protein-Protein Interactions Drug Discovery Research Group (unit director: Prof. David E. Thurston). As a co-PI of a CR UK Small Molecule Drug Discovery Initiative program she led the research aimed at discovering protein-protein inhibitors of transcriptional factors such as Hypoxia Inducible Factor 1 (HIF-1) and Signal Transducer and Activator of Transcription 3 (STAT3 ).

In January 2012 she took up the position at the Karolinska Institutet as Assistant Professor in Chemical Biology and a Principal Investigator (Group Leader) within the Centre for Advanced Cancer Therapies (ACT), MTC Department.

Research description

 

HOW TRANSCRIPTIONAL REGULATORS CONTROL GENE EXPRESSION PROGRAMS and CELL FATE in NORMAL and MALIGNANT CELLS

How the transcriptional machinery orchestrates gene expression programs during development, renewal and in response to environmental signals is one of the  outstanding questions in biology. I tackle this fundamental problem by focusing on determining at the molecular level the mechanisms regulating the interactions between transcription factors and their interactions with co-factors, especially with epigenetic regulators.

My work encompasses chemistry, biochemistry, biophysics and structural biology. The ultimate goal is to develop therapeutic agents to treat human diseases, and new approaches for regenerative medicine.

I am currently working on two key molecular machineries: (1) MYC and other members of its Basic-Helix-Loop-Helix-Zipper (bHLHZip) network of transcription factors; and (2) the SWI/SNF (BAF) chromatin remodelling complexes.

Our work on c-MYC is focused on determining: how transcription factor cooperation leads to gene repression; and how the MYC extended network of bHLHLZ transcription factors, i.e., the c-MYC like MONDOA/ChREBP paralogs, regulate metabolism.

Projects on the SWI/SNF complexes are currently directed to understand: how these chromatin remodelling complexes control MYC gene expression; and how the BAF60 and the BAF155/170 subunits, respectively, mediates interactions with diverse transcription factors with roles in cellular processes, such as regeneration, cardiac development and metabolism. We are also exploring ways to target the SWI/SNF complexes for the development of new therapies.

RESEARCH COLLABORATIONS (alphabetical order)

  • Prof. Don Ayer, Huntsman Cancer Institute, University of Utah, USA; 
  • Dr Mark Bycroft, University of Cambridge, Cambridge, UK; 
  • Prof. Gerard Evan, University of Cambridge, UK; 
  • Prof. Laura Itzhaki, University of Cambridge, Cambridge, UK; 
  • Prof. Sophia Yaliraki, Imperial College London, UK; 
  • Prof. Lars-Gunnar Larsson, Karolinska Institutet, Sweden.

Notes:

The structure of INI1/hSNF5 RPT1 and its interactions with the c-MYC:MAX heterodimer provide insights into the interplay between MYC and the SWI/SNF chromatin remodeling complex.  Sammak S, Allen MD, Hamdani N, Bycroft M, Zinzalla G. FEBS J. 2018 11;285(22):4165-4180.  

This publication is recommended in F1000Prime as being of special significance in its field by F1000 Faculty Member Wolfgang Jahnke (Novartis Institutes for Biomedical Research, Basel, Switzerland).

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