Name: Mala Maini
Institution: University College London
Location: London, UK
Twitter (if applicable): @maini_lab
Orcid (if applicable): 0000-0001-6384-1462
Could you tell me a little bit about your research and what it entails?
Our research is mainly based on samples that patients with HBV or liver cancer kindly donate and we are really grateful to them and all the staff who make this possible. Using techniques like high-dimensional flow cytometry, we can get a lot of information from tiny numbers of cells freshly extracted from liver biopsies, for example. We study the cellular interactions within the liver to determine what underpins the failure of immune control and consequent necroinflammatory damage driving chronic hepatitis B and liver cancer. Based on our findings we test out new immunotherapeutic approaches in the laboratory to boost immune control. We are focusing on the cross-talk between different immune cell types and the influences of the local microenvironment; these insights could be relevant to understanding the balance between immunity and immunopathology in other liver diseases. Some recent examples of our work are:
- IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection
- T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System
- Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host
- CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver
- Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells
How did you come to be interested in viral hepatitis?
I’ve specialised in looking after patients with viral hepatitis for decades and was frustrated by the lack of good treatment options for them. After stepping out of my clinical job to do a PhD in basic aspects of T cell immunology with Peter Beverley, I wanted to try to apply that knowledge to an infection relevant to patients in my clinics. Several other serendipitous twists cemented that resolve.
I attended my first international conference and heard Frank Chisari presenting elegant work done in his lab by Luca Guidotti, showing how T cells could clear hepatitis B without damaging hepatocytes. I contacted Andrew McMichael in Oxford and persuaded them to make us a new state-of-the-art reagent (an HLA-peptide tetramer) to study HBV-specific T cells, and applied for a fellowship. I didn’t get the fellowship first time round, but got some bridging funding from Persephone Borrow at the Jenner institute. Simultaneously, Antonio Bertoletti, whose publications on HBV T cells had been another inspiration, unexpectedly moved to UCL and from that moment on, there was no stopping us! (For example, https://www.ncbi.nlm.nih.gov/pubmed/10579980 and https://www.ncbi.nlm.nih.gov/pubmed/10770795)
What do you see as the biggest accomplishment in your field in the past few years?
There has been really exciting progress in immunotherapy in recent times, which is starting to be applied to hepatitis B. The use of checkpoint inhibitors like PD-1 blockade to reinvigorate anti-tumour immunity in patients with several types of cancer has been a transformative demonstration of the power of immunotherapy. A recent trial has shown that this approach also holds promise for hepatocellular carcinoma, which is one of the major complications of hepatitis B and the second leading cause of cancer deaths worldwide. We participated in the first-in-man testing of genetically engineered T cells for hepatitis B-related hepatocellular carcinoma, another innovative therapy for this cancer. Hopefully our research will continue to inform further refinements in hepatitis B immunotherapy in the coming years.
What do you see as the main challenges for research in your field in the coming years?
Deciphering the complexity of immune regulation in order to select the best targets to safely boost control of HBV and liver cancer is an ongoing challenge. Continued access to liver tissue (from patient biopsies and surgical specimens) is vital to assess interactions between immune responses and the virus within the specialised niche of the liver. Hepatitis B is gaining more attention but there is still work to be done to convince funding bodies and others how vital and neglected this area is; I still get people saying “there’s a preventative vaccine for this infection, why is it a high priority?” Thankfully there’s been more press highlighting the huge burden of 240 million people already chronically infected for whom the preventative vaccine is no help.
The Maini Lab supporting the NOhep campaign to eliminate viral hepatitis by 2030.
What personal career achievement are you most proud of? Why?
I’m not proud of a personal career achievement but of the constantly evolving team of researchers I’ve trained and of all of our hard work and achievements together. It’s still a massive thrill every time we get the results of a new experiment, or find a relevant clue from the literature, which fits another piece into the ever-fascinating puzzle of the immune system. I love to see the dedication and collaborative spirit of my group; we’ve had so much fun together over many years. And seeing our findings influencing the direction of other’s research and the development of therapies is really satisfying. Securing recognition and funding to keep all this going is always a relief, so getting a Wellcome Trust Senior Investigator award was a big milestone on that front.