H. Michael Shepard
H. Michael Shepard, PhD is an American cancer researcher who was shared the 2009 Warren Alpert Award by Harvard Medical School with Axel Ullrich, Dennis Slamon and Robert Weinberg, and the 2019 Lasker Clinical research award, which he shared with Slamon and Ullrich for trastuzumab/Herceptin.
Education and Career
He is also a Fellow of the Kennedy Institute of Rheumatology/University of Oxford and Adjunct Faculty at Indiana University, Bloomington. Shepard holds a bachelor's degree from the University of California, Davis, and a Ph.D. from Indiana University, where he was also a Damon Runyon Cancer Research Foundation Fellow. His introduction to biotechnology came when he joined Genentech in 1980, where most of the work leading to trastuzumab/Herceptin was done. Following Genentech, he has been a Founder or Principal in several biotech companies. These include Canji, Inc. (Gene therapy using tumor suppressor genes), NewBiotics (Tumor-suppressor dependent overexpression of enzymes that activate prodrugs), Receptor Biologix (Splice variants engineered as ligand traps), and Halozyme (enzymes that target the extracellular matrix in solid tumors). Shepard continues his work in translational medicine and consults with biotech and biopharma focusing on biomarker-driven treatments for cancer and other diseases.
Background for Discovery of trastuzumab/Herceptin.
Following Ullrich's characterization of the HER2 protooncogene, Shepard collaborated with Ullrich and Slamon to explore possible molecular links to breast cancer. Slamon discovered, along with other colleagues in the field, that HER2 overexpression in breast cancer predicts shorter survival. However, a lot of proteins are overexpressed in cancer cells and correlate with shorter survival. Therefore, the remaining question was: Is the overexpression of HER2 a significant driver in tumor progression and how does this work? Shepard and Hudziak discovered that HER2 overexpression not only drives tumorigenesis through cell proliferation, but endows tumor cells with resistance to innate immune system protections, resulting in more rapid tumor progression (partly in collaboration with Prof. Hans Schreiber at the University of Chicago). Shepard and colleagues at Genentech (Paul Carter, Gail Lewis) then invented trastuzumab/Herceptin, the first humanized monoclonal antibody to successfully treat solid tumors, and the first approved tyrosine kinase inhibitor. This innovation reduces the risk of recurrence and extends survival time for patients with metastatic as well as early-stage HER2-positive malignancies. About 3 million women have received the treatment since it became available, many of them with significant benefit. Trastuzumab/Herceptin has become the dominant model of antibody therapeutics and biomarker-driven drug discovery.
Other activity
Shepard has made seminal contributions to gene therapy of cancer, to tumor suppressor gene targeted small molecule therapeutics, and to drugs which target the tumor extracellular matrix. He continues his work, now expanding successful treatment paradigms used in cancer to approach inflammatory and autoimmune diseases. Shepard also consults for biopharma companies on how to develop meaningful biomarkers that will speed drug development. Education is another of Dr. Shepard's passions, and he gives lectures meant to teach, stimulate, excite and give hope to interested scientists and students, and to cancer patients who need to more about how the disease works. Dr. Shepard has co-authored many peer-reviewed publications and patents.
Patents
- U.S. Patent 7,138,388 — Methods to treat autoimmune and inflammatory conditions
- U.S. Patent 7,105,156 — Method of using an adenoviral vector encoding a retinoblastoma protein to treat hyperproliferating cells
- U.S. Patent 6,946,259 — Compositions and methods for treating cells having double minute DNA
- U.S. Patent 6,683,061 — Enzyme catalyzed therapeutic activation
- U.S. Patent 6,551,585 — Use of tumor necrosis factor as an adjuvant
- U.S. Patent 6,495,553 — Methods and compositions for overcoming resistance to biologic and chemotherapy
- U.S. Patent 6,399,063 — Monoclonal antibodies directed to the HER2 receptor
- U.S. Patent 6,387,371 — Monoclonal antibodies directed to the HER2 receptor
- U.S. Patent 6,348,352 — Methods for selectively transducing pathologic mammalian cells using a tumor suppressor gene
- U.S. Patent 6,339,151 — Enzyme catalyzed therapeutic agents
- U.S. Patent 6,333,169 — HER2 extracellular domain
- U.S. Patent 6,331,524 — Organ-specific targeting of cationic amphiphile / DNA complexes for gene therapy
- U.S. Patent 6,245,750 — Enzyme catalyzed therapeutic agents
- U.S. Patent 6,165,464 — Monoclonal antibodies directed to the HER2 receptor
- U.S. Patent 6,159,706 — Application of enzyme prodrugs as anti-infective agents
- U.S. Patent 6,015,567 — HER2 extracellular domain
- U.S. Patent 5,851,991 — Therapeutic use of the retinoblastoma susceptibility gene product
- U.S. Patent 5,837,520 — Method of purification of viral vectors
- U.S. Patent 5,772,997 — Monoclonal antibodies directed to the HER2 receptor
- U.S. Patent 5,720,954 — Monoclonal antibodies directed to the HER2 receptor
- U.S. Patent 5,710,255 — Characterization of a novel anti-p110.sup.RB monoclonal antibody
- U.S. Patent 5,677,171 — Monoclonal antibodies directed to the HER2 receptor
- U.S. Patent 4,963,354 — Use of tumor necrosis factor (TNF) as an adjuvant
- U.S. Patent 4,808,402 — Method and compositions for modulating neovascularization