A recipient of the Harvard Medical School Warren Alpert Award and the Lasker Prize for Clinical Medicine, Shepard began his career at Genentech in 1980. After several years of successfully cloning interferons and other potential therapeutics, Shepard initiated a group at Genentech with the aim of understanding mechanisms of sensitivity and resistance to various immune-based therapeutics (TNF-a, IFN-gamma). This work resulted in showing that overexpression of HER2 results in resistance to cytotoxicity by TNF/macrophages, and the discovery of the MAB 4D5, which became Herceptin (Hcp), which reversed this resistance. Dr. Shepard led the teams that characterized this MAb’s biologic activity, created humanized versions, and brought the antibody into clinical trials. Hcp is the first MAb effective against solid tumors to reach approval. Hcp also proved that tyrosine kinases are targets in cancer. Finally, Hcp initiated the 'era’ of personalized medicine with its ‘Herceptest' for overexpression of HER2. This work lead to Dr. Shepard’s recognition as a recipient of Harvard's Alpert Prize in 2007. With this work as background, Dr. Shepard joined Canji in 1992, and brought the first adenovirus gene therapy into clinical trials (for ovarian cancer). Dr. Shepard has founded two biotech companies. NewBiotics: Creating small molecule cancer therapeutics that target cancer targets that are overexpressed following the inactivation of tumor suppressor genes; and Receptor Biologix: Which pioneered the concept of 'pan-HER' inhibition (single drug inhibiting the EGFR, HER2, and HER3). At Halozyme, Dr. Shepard worked with other management (and partners) to obtain three European drug approvals and one US drug approval for EnhanzeTM technology for subcutaneous drug delivery. Dr. Shepard's team at Halozyme also created a platform for discovering tumor specific therapeutics, based upon the physical/chemical properties of the tumor extracellular matrix. The product candidates to emerge from this platform include tumor-specific MABs, and enzyme therapeutics for immuno-oncology. Shepard received the Lasker Prize in Clinical Medicine in 2019 for his work on Herceptin/trastuzumab.