DesignationProfessor, Duke-NUS Medical School SingaporeDirector, Translational Immunology InstituteUCAN-A Chair, President, Eureka Institute
Faculty BioMy field of research is to understand and manipulate human immunity to ultimately and tangibly improve Health. I have developed a comprehensive technology platform which pivots on high dimensionality approaches, including cytometry, 10X single cell next generation RNA sequencing and in vitro functional modelling. We have developed Artificial Intelligence (AI) tools to distill mechanistically and clinically relevant knowledge from the interfaces among these high complexity datasets and the clinical data. By leveraging on this platform, validated predictive modelling is developed. This platform enables fundamental progress in several translationally relevant, first in class scientific contributions, which span across disease areas ranging from Autoimmunity to Cancer. It is important to emphasise the unifying conceptual framework to conceive mechanistic and therapeutic manipulations of the human immunome not as an intervention on discrete pathways which stand isolated and can be switched on and off, but rather as the sophisticated manipulation of a gradient of pathways and cell subsets which are inextricably interlaced, and can be modulated within a continuum of intensity, comparable to what a rheostat does to the intensity of lighting in a room. I look at the architecture of the Immune System and its therapeutic manipulation by evolving from fragmentation to a continuum gradient balanced on homeostasis and tilted by perturbations such as disease or even conventional therapy.My contribution is to have conceived and evolved this concept to tangible applications. Each of the projects can bring a solution to unmet needs. Combined, the platform advances Science by looking holistically and with high dimensionality at mechanisms of immune imbalances, thus leading to the identification of novel immune therapeutic targets which we are developing for restoration of immune homeostasis. Some of the most advanced projects include: 1) Defining for the first time an AI-driven, high dimensional architecture of the healthy Immunome (EPIC), and assessing the effects of Disease as perturbations of this architecture; 2) Conceiving and developing Chimeric Antigen Receptor Treg (CARTreg) as an entirely novel approach to cellular immunotherapy of transplant rejection, graft versus host disease and systemic autoimmunity; 3) Conceiving and developing new composition of matter and next steps for the development to commercial fruition of a Phase IIb – ready, first in class immunotherapy for Rheumatoid Arthritis; 4) A theragnostic platform to predict the opportunity to withdraw patients with arthritis from biologics. My work has been published in most relevant Journals of high calibre (IF of 43 and 8000 citations), and generated a diverse portfolio of more than 100 patents. This work is the foundation of my entrepreneurial activities.I am very active in education. Indeed, a most rewarding part of my professional life is to infect others with my passion for what I do, and to share my experiences, my successes and my failures. I am the co-founder and President of the Eureka Institute for Translational Medicine, an international organization focused on the advancement of Translational Medicine through research, education and policy shaping.
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