James Gorman
Principal Investigator, Brain Targeting Program WYSS Institute, Harvard Medical School
Jim is Principal Investigator on the Wyss Institute Brain Targeting Program (BTP). In this role, Jim leads a team developing new approaches to transport drugs through the blood brain barrier (BBB) into the CNS. The BTP collaborates broadly, using its brain shuttles to develop improved brain-targeted therapeutics to dramatically improve treatment of brain diseases. A major focus of the BTP is fostering pre-competitive collaboration between diverse pharmaceutical companies, academics, and philanthropists to accelerate progress in brain delivery. The vision shared by Jim and his BTP colleagues is to make available to drug developers the engineering tools and expertise to target any drug to any brain cell type and subcellular compartment for the treatment of any brain disease.
Jim worked for 7 years in licensing, acquisitions, portfolio management and strategic initiatives at Abbott Labs (now Abbvie). He oversaw antibody technology platform development and therapeutic R&D portfolio management, from target identification and validation through pre-clinical drug discovery and development. There, he received the Abbott President’s Award for his role in initiating, championing and executing the 2001 acquisition of the blockbuster anti-TNF antibody Humira®, in 2021 the top-selling drug worldwide, with annual sales of $20.7 billion. Jim formed and led Abbott’s Antibody Strategy Team and then co-chaired the Portfolio Management Committee, initiating and overseeing a process that led to the launch of ten new inflammation and oncology discovery projects. After leaving Abbott, he co-founded and served as CEO of two biotech startups. BioAssets Development developed antibody anti-inflammatory therapies for treatment of pain in patients with disk herniation and sciatica, and was acquired by Cephalon. 121 Bio developed single domain antibodies for use in immune-oncology, and was acquired by Agenus.
Jim obtained his M.D. and Ph.D. degrees at Harvard Medical School, where he researched molecular genetics of antibody formation in the lab of Dr. Frederick Alt. He graduated summa cum laude from Yale University.
Seminars
- Profiling TfR, IGF1R, LRP1 and emerging BBB targets across human brain microvessels reveals conserved disease-state expression but high inter-individual variability with potential implications for patient stratification
- Understanding order-of-magnitude variability in receptor abundance and its potential impacts on binding kinetics, target engagement, and dose–exposure relationships for shuttle-enabled therapeutics
- Engineering and benchmarking dual-target brain shuttles to optimize transcytosis efficiency while balancing affinity, valency, and receptor trafficking dynamics
- Evaluating modality-specific considerations for dual shuttles including antibody and oligonucleotide payload delivery, and defining engineering principles to enhance target engagement while avoiding rapid plasma clearance, reduced BBB transport or decreased neuronal uptake
- Which alternative BBB receptors (e.g. CD98hc, insulin receptor, LRP1, basigin) show the most promise beyond TfR1 for achieving sufficient brain uptake without compromizing safety or peripheral PK?
- How can we optimize receptor affinity, valency, and trafficking profiles to balance efficient transcytosis with minimal lysosomal degradation or target-mediated clearance?
- What preclinical models and translational biomarkers are most predictive for comparing receptor performance and de-risking clinical success across different shuttle platforms?
- How should developers prioritize receptor selection based on modality (e.g. antibodies, enzymes, oligonucleotides) and indication-specific needs for brain distribution and cellular targeting
