Dr Vikramaditya G Yadav in 100 most influential people in drug development and manufacturing

He is one of eight Indian-origin achievers to be recognised and is the youngest member of this illustrious list

Dr Vikramaditya G Yadav, Assistant Professor in the Department of Chemical & Biological Engineering at the University of British Columbia (UBC) in Canada has been recognised by Medicine Maker for his formalisation of ‘biosynthonics’, a novel paradigm for drug discovery and development based on metabolic and enzyme engineering.

Youngest Indian in list

Yadav is one of eight Indian-origin achievers to be recognised and is the youngest member of Medicine Maker’s illustrious list.

Incidentally, Yadav shares the Medicine Maker  honour with three of his professors from MIT— Dr Robert Langer, Dr Charles Cooney and Dr Bernhardt Trout. He was Cooney’s teaching assistant for a course on downstream processing, and Yadav’s experience in the laboratory of Langer greatly shaped his scientific views. Trout taught thermodynamics and statistical mechanics to Yadav during the latter’s first year at MIT.

Contributing to progress

Significant advances have been made in analytical chemistry, genome sequencing and assembly, flow chemistry, chemi- and bioinformatics, metabolic engineering and synthetic chemistry; and the raw computing power that is available for drug research has witnessed exponential improvements.

Biosynthonics, Yadav’s field of work, integrates these parallel innovations into a single platform in order to translate a vastly higher number of small molecule drugs to the bedside. The platform could prove to be particularly effective in tapping into the chemistry of natural products, a veritable treasure chest of therapeutic compounds.

Biosynthonics comprises four principle domains:

1. Design
2. Synthesis
3. Exploration
4. Integration

Design encompasses the selection of electronic features and their steric optimisation onto a rigid molecular framework in order to ensure optimal binding to a specific biological target. The conceptual underpinning this exercise is rooted in fragment – based pharmacophore modeling and all steps are completed in silico. The pharmacophores so-designed are then synthesised in a microbial chassis that has been carefully constructed via metabolic engineering. The third domain of biosynthonics – exploration—expands the biosynthetic ensemble for metabolic engineering through a systematic search of nature’s metabolic landscape. In the fourth domain, the biosynthesised pharmacophores are employed as inputs for conventional target-oriented chemical synthesis (TOS). This integration facilitates access to precise regions of chemical space – either a single molecule or a small assortment of molecules exhibiting minor variations on a chemical theme.

Yadav has also been recognised for his pioneering work on the development of more accurate and rapid pre-clinical screening platforms for identifying drugs targeting neurodegeneration. He is collaborating with colleagues from the biopharma industry and the Faculty of Pharmaceutical Science to construct artificial human brains in a variety of formats, one of which is a brain-on-chip. His team is employing stem cell and tissue engineering, micro – manufacturing and mathematical modeling to design and assemble a brain-on-chip device that mimics the human brain. A brain-on-chip is a type of organ-on-chip device, the kinds of which have already attracted the attention of the pharma industry. Organs-on-chips are miniaturised, three-dimensional models of human tissue that recapitulate the spatiotemporal complexities of the tissue microenvironment as they occur within the body. This provides a highly context-specific platform to test and validate lead compounds, which improves the success rate of compounds in the clinic.

Yadav plans to utilise this device to investigate fundamental details about neurotransmission and test lead compounds targeting two prominent neurodegenerative disorders, chronic traumatic encephalopathy (CTE) and frontotemporal degeneration (FTD) in a high-throughput manner. The co-application of mathematical modeling and analysis with key concepts from stem cell bioengineering, micro-manufacturing and engineering design represents a methodological advancement that will potentially open new frontiers in biomedical engineering.

An illustrious career

His achievements in the course of his glorious career have been many. His work has gained international recognition. He took a keen interest in low – cost science and translational research, and authored a business plan to commercialise a pharma manufacturing technology in resource-constrained settings. This earned him prestigious awards like the ACS Kauffman Foundation Entrepreneurship Prize and the MIT Legatum Fellowship for his business plan, both in 2012.

At MIT, Yadav also flourished as a teacher, author and opinion leader, and was bestowed with the Edward Merrill Prize for Teaching Excellence in 2010, the gold medal from the Biochemical Society, UK in 2012 for his authorship of a general interest article on drug discovery and development, and the SciFinder Future Leader in Chemistry prize in 2012.

He currently serves as the Vice-Chair of the Biotechnology Division of the Chemical Institute of Canada, and was recently honoured by Green College at UBC as one of its first Green College Leading Edge Scholars. He was also awarded the Wall Scholars Award by the Peter Wall Institute for Advanced Studies earlier this year for the Interdisciplinarity and wide-ranging impact of his research.

Moving forward

Yadav, a strong advocate of philanthropic science, hopes to play his part in ensuring people throughout the developing world, especially in his homeland, have access to the very best therapeutics at the lowest prices. He hopes that his team continues in similar stead and successfully translates technological innovations to the pharma industry.