NIHR SRMRC Lecture

08 December 2016

Prof Andrew Baird (Dept of Surgery, University of California, San Diego)

“A Uniquely-Human Response to Injury, Infection and Inflammation Defined by the Emergence of Uniquely-Human Genes During Human Evolution”

Thursday 8th December

12:00 – 13:00

IBR Seminar Room, College of Medical and Dental Sciences, University of Birmingham

Synopsis of research:

There is a sub-class of genes called “uniquely-human genes” that are only found in the hominid genome. Arising after hominid divergence from great apes, these genes are not restricted to the human central nervous system, but instead appear widely expressed in locations like bone marrow and cells like circulating leukocytes.

Noting that these cells are uniquely suited to address the (injury and infection) sequelae of new “hominid” behaviors, we investigated whether the emergence of these new genes could gauge injury, infection and inflammation homeostasis.

The findings impact understanding the origin of complex human disease, underscore certain limitations to models of human disease and suggest that the contribution of uniquely human genes to complex human disease deserves further study.

Prof A Baird biography:

Originally trained as a steroid biochemist/endocrinologst in Montreal Canada (McGill University 1976-1980), Professor Baird started his research career at the Salk Institute (San Diego, California) in the laboratories of Professor Roger Guillemin (Nobel,1977). There, he carried out basic research on the control of cell growth and function in the early days of cell culture in work that was going to lead to the isolation and characterization of the first-ever angiogenic factor called basic fibroblast growth factor (FGF2).

He was then involved in characterizing FGF2 receptors, identifying the FGF2 promoter, generating the first transgenic mice over-expressing the FGF2 gene and establishing the first structure-function studies characterizing FGF2 ligand-receptor interactions. With this information, he identified a series of FGF2 agonists and antagonists for wound healing, injury and tissue regeneration.

His work in developing FGF2 therapeutics was instrumental in understanding why growth factors were not the huge bio-therapeutic successes expected when they were first discovered. This experience turned his attention to the unique challenges of drug delivery for growth factor therapeutics and specifically, the spatio-temporal needs for multiple factors at multiple times.

To this end he turned his attention from protein to gene therapeutics while developing new vectors for gene delivery, new processes to create gene delivery vectors using directed evolution, new modes of gene targeting and gene delivery and discovering a small molecule inhibitor of macrophage-migration inhibiting factor (MIF) that is currently in drug development for inflammatory disease.

His laboratories currently work on human injury and inflammation, and the development of techniques to identify genes of the “therapeutome”. These are genes that encode proteins with direct and intrinsic therapeutic value, specifically for tissue repair.

His recent discoveries of unique set of “human-only genes” in human inflammation breaks new ground by recognizing that humans have unique sets of genes that are involved in response to injury. This novel concept is particularly innovative given that injury is perceived as evolutionary conserved and its mechanisms evident from the simplest organisms to all mammals.

That being said, this innovative concept underscores the important role of human-based studies in drug development and likely provides new insight into the limited success of advanced therapeutics. In 2016, he was recognized by the JWC-World Union of Wound Healing Societies (WUWHS) with the Wound Care Innovation Award, given every four years for the most significant innovation in wound healing.

1976-1980 PhD Graduate student McGill University, Montreal, Canada

1980-1990 Post Doc, Junior Faculty,  Salk Institute, San Diego California

1990-1995 Professor, Department Chair, The Whittier Institute, San Diego California

1995-2001 Founder, Chief Scientific Officer (1)Prizm Pharmaceuticals, (2) Tissue Repair Company, (3) Ciblex Corporation

2001-2005 Professor Kings College London and U. Birmingham

2007-present Professor & Vice Chair (Surgery) UC San Diego