Dr. Biswas completed his Ph.D. in Biotechnology (Cellular Immunology) at Banaras Hindu University, India followed by postdoctoral studies at the Istituto di Ricerche Farmacologiche "Mario Negri", Milan (Italy) working on the first molecular characterization of tumor associated macrophages in group of Prof Alberto Mantovani and Antonio Sica. During this period, he was awarded a fellowship of the Alfredo Leonardi and G. Pfeiffer Foundation. In 2005, he joined the Bioinformatics Institute of A*STAR in Singapore as Research Scientist (In-Charge) of the (Immune)Cell Interaction group. From 2007 onwards, he is a Principal Investigator at the Singapore Immunology Network (SIgN, A*STAR), heading the Human Innate Immunity Lab. He has held adjunct associate professor position at the Department of Microbiology, National University of Singapore and LKC School of Medicine, Nanyang Technological University, Singapore. He is also a visiting Professor at Humanitas University (Medical School), Milan, Italy. His research interest is in monocyte-macrophages biology and their role in in selected human disease.
- Visiting Professor, Humanitas University, Milan, Italy
Keywords: Monocyte/macrophage, inflammation and cancer, immunotherapy, immunometabolism.
Monocytes and macrophages are versatile cells that not only serve as a first line of host defence (against pathogens and cancer) but also have important homeostatic functions in organogenesis and development [Ginhoux,…Biswas, Nat Immunol 2016]. To perform these varied roles, these cells are endowed with remarkable functional diversity such as triggering an immune-inflammatory response, phagocytosizing and killing pathogens, tissue remodelling and repair, and orchestrate immunoregulation(Fig 1). However, such functions are tightly controlled (in magnitude and time and context) and a result of an activation response(s) to a particular microenvironmental stimuli(s) that ‘polarize’ these cells to the particular functional phenotype [Biswas & Mantovani, Nat Immunol 2010]. Importantly, a dysregulation in these tightly regulated activation phenotype and functions is often associated with pathogenesis. Thus, understanding the dysregulated phenotype of these cells and the mechanism(s) that drive this process provides an important insight into the molecular basis of pathogenesis, which in turn, can provide immune signatures (biomarkers) associated the disease as well as potential therapeutic targets. Work in our lab is focussed towards investigating the following questions:
- How do monocytes/macrophages perceive different microenvironmental cues and translate them into ‘tailored’ response(s)?
- >How does a dysregulation in this process contribute to pathogenesis?
- What are the mechanisms, pathways and molecules that orchestrate monocyte/macrophage activation phenotype(s) as well as their dysregulation in selected human diseases?
- Can these molecules be used to ‘reprogram’ myeloid cells to control disease progression?
Fig.1. The hallmarks of macrophage activation and function diversity. Upon activation with particular stimuli, macrophages respond by adopting specific functional phenotypes that are specialized in performing specific functions as shown in the figure. Red: stimuli; Blue: Molecules expressed by macrophages. Black italics: examples of macrophages with the corresponding specialized function(s).
We are addressing the above questions by studying human diseases like cancer, metabolic disease (obesity and Type 2 Diabetes) and sepsis using a combination of patient cohorts, in vitro models and preclinical mice/humanized mice models.
Fig.2. Schematic outline of the research approach taken for our various projects (see text for details).
To this end, we take a Systems Immunology approach (Fig 2), starting from deep immunoprofiling of patients (using a combination of state-of-the-art, high-dimensional, multi-parametric approaches available under the SIgN Immunomonitoring Platform), which leads to identification of myeloid subsets and their immune signatures (=potential biomarkers/liquid biopsies) for the particular disease and/or treatment response (depending on the cohort) studied. This is followed by mechanistic studies (using in vitro models, molecular pathway dissection, etc) to understand what drives the above immune signature and to identify potential therapeutic targets thereof. These targets are then tested in vivo using preclinical mice models (e.g. cancer models) or humanized mice models (available through the SIgN HuNIT platform) and humanized biologics (e.g. humanized checkpoint antibodies, in collaboration with the SIgN Human Monoclonal antibody platform) to see if disease modulation can be achieved in vivo. Further development of these biomarkers and targets are facilitated by the Translational Immunology group in collaboration with Industry partners.
Most of the ongoing projects have a clinical/translational outlook with strong collaborations with clinical partners (at the local hospitals and the cancer centers) as well as multiple international/local academic and industry collaborations. Our lab is also a part of several national research consortiums like VICTORY (Virus-Induced Cancers: Translational Oncology Research and immunologY), CITI (Cancer ImmunoTherapy Imaging), ToxMAD and the Human Functional Genomics Project (international).
- Deep immunoprofiling of human tumor microenvironment and its immunomonitoring upon cancer immunotherapy.
- Immunometabolic regulation of metabolic disease (obesity, type 2 diabetes) and cancer.
- “Trained immunity” in human disease.
Funding: SIgN core funding; JCO (A*STAR); LCG-NMRC, IAF-PP and industry partners.
||Manprit Kaur DHILLON
||Jyue Yuan LIM
||Hedayathulla Bin RAHMATHULLA
Publications Publications_Subhra Biswas
(last updated 30 May 2023)