CV Science

Uzma Ayesha -Hasan PhD Immunology and Molecular Biology University of London, UK

Course and current status

Biography: Principle Investigator for Inserm at the Centre International de Recherche en Infectiologie and also the Centre Leon Berard, Lyon, France. For the last ten years, I have been working in the field of innate immunity and cancer. My career path started at Kings College then at St Bart's and Royal London Medical School where I was awarded her PhD in Immunology. My post doctoral training was based at Schering Plough under the direction of Giorgio Trinchieri working in the field of Toll Like Receptors. I worked on HPV, EBV and HBV immune escape from innate receptor sensing at IARC, WHO, France. During my stay I also won an EMBO fellowship to work in the lab of Ruslan Medzhitov, Yale. These experiences led to forming a theme within Inserm in which I continue to understand how chronic diseases can alter immune responses.

2022 Coordinator LICL, CRCL, Lyon and HBV and Innate immunity, CIRI, Lyon

I currently have two posts; one is as a PI at the Centre International de Recherche en Infectiologie (CIRI) focused on studying oncoviral deregulation of innate immunity. Here, I work on several projects that linked immunological characterization in HBV infected patients, using CRISPR screens to examine the molecular pathways that altered by its viral proteins. I have recently won grants to study the role of HBV on NK and B cells in patients and will supervise a study in collaboration with the Civil Hospitals in Lyon and Limoges. My other post is at the cancer hospital in Lyon (Centre Leon Berard) at the Lyon Immunotherapy for Cancer Laboratory (LICL).  The creation of the LICL in Lyon is to expand our knowledge by characterizing immune responses in cancer patients who receive immunotherapy. The arrival of the LICL with its cutting-edge technologies and scientific valorization from bench to bedside is the main driver that has led me to join and help coordinate projects. My missions as coordinator are to facilitate the running, valorization, funding as well as to solidify interactions between clinicians, researchers and industry for smooth running of the LICL. I work closely with the LICL director Christophe Caux, help manage the in-silico studies he heads, support the translational cytometry research platform (Innovation in Immunomonitoring and Immunotherapies) run by Christine Caux and the Multiplex Immuno-Fluorescence In Situ (MIFIS) platform lead by Bertrand Dubois. I will also help to establish the Tumor Immune Functions EX VIVO platform with Nathalie Bendriss-Vermare.

2016-2021 Team Immunité innée dans les maladies autoimmunes et infectieuse, CIRI. Current projects include co-ordination and research on NK cell exhaustion by HBV in patients, CRISPR Cas9 screens.

2009-2015: Principle Investigator CR1, Inserm U851:  Team: Oncoviruses and Innate Immunity. HPV and HBV deregulation of innate sensing.

2011: Habilitation a Diriger Les Recherches (HDR) University Claude Bernard Lyon I (UCLB)

2005-2008: Visiting Scientist at International Agency on research for Cancer, Lyon, France. “The role of Toll Like receptors in infectious cancers”.

2001-2004: Scientist at Schering Plough, Lyon, France and Kenilworth, New Jersey, USA. “Toll Like Receptors in HTS: Identification of new TLR agonists for cancer therapy”. 

2000-2001: Research Associate Cytos, Zurich, Switzerland. “HTS Delphi system for identification of new chemokines”.

1997-2001: PhD student St Batholomews and the Royal London Medical School , London, UK; “DNA vaccination for varicella-zoster-virus”. 

1992-1996/7: Program immunology* at Kings College London, London, UK. * BSc awarded 2.1.

Scientific summary

Chronic diseases and Immunity

Research

Oncoviruses and cancer cells have the capacity to escape immune surveillance and promote cellular transformation in order to persist and progress in humans. Innate immune responses play a crucial role in the control of viral replication and are required for a timely orchestration of specific adaptive responses against the infection. The innate immune system can sense pathogen components via the Toll Like Receptor (TLR) family and cytosolic receptors. We observed that the human papillomavirus type 16 (HPV16) (associated with cervical cancer), a virus that infects the basal epithelium, can effectively deregulate the expression and function of Toll Like Receptor 9 (TLR9). We have also shown that TLR9 is deregulated by hepatitis B virus as well as another double-stranded DNA sensor,  AIM2.  Another ambitious goal will be to determine whether TLR9 has a role in regulating the cell cycle in cancer, in particular, to determine the mechanisms that induce events leading to cell death. This highlights a new function of Toll Like Receptors and underscores why TLR9 is targeted in chronic diseases. We have also shown that NK cells from HBV infected patients display an exhaustive phenotype similary to those described in T cells.  More recently, by performing CRISPR/Cas9 screens we have identified new genes that render tumour cells resistant to primary NK cell killing.

Clinic

All studies are conducted in humans and require intensive use of primary human cell cultures in P2/P3 facilities, and tight collaboration with labs and hospitals based nationally and internationally. Most importantly, all our research is corroborated in the clinic with inclusions from patients. Our studies in TLR9-B and NK cell deregulation by HBV have been done with the CHU hospital in Limoges. Here we set up a study to recruit blood, serum and PAX/RNA samples from patients with Chronic Hepatitis B infection. In addition, in collaboration with the IARC, Lyon, we examined whether certain polymorphisms in innate receptors will influence the risk of cervical cancer using DNA samples from women in different regions of the world. The TLR9 cell cycle project is being performed in collaboration with the CRCL and Kings College in London.Work carried out for the LICL involves co-ordinating all the platform and research PIs on projects related to immune therapy in cancer patients and trying to identify immune related signatures in cancer patients that respond vs non respondors to first line or second immunotherapy treatments.