H. Michael Shepard

H. Michael Shepard is an American cancer researcher.

He holds a bachelor's degree from the University of California, Davis, and his Ph.D. from Indiana University. Dr. Shepard was a Damon Runyon Cancer Research Foundation Fellow at Indiana University. His introduction to biotechnology came when he joined Genentech in 1980. Following Genentech, he has been a Founder or Principal in several biotech companies. These include Canji, Inc., NewBiotics, Receptor Biologix, and Halozyme.

Shepard was awarded a Lasker Clinical Research award in 2019, which he shared with Dennis Slamon and Axel Ullrich. Following Ullrich’s characterization of the HER2 protooncogene, Shepard collaborated with Ullrich and Slamon to explore possible 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 too much HER2 made tumor cells grow better. Then made a key discovery about how HER2 can cause resistance to immune cell killing of tumor cells. Overexpression of HER2 makes cells resistant to killing by macrophages, which are the first line of defense against cancer. This work was done in collaboration with Dr. Hans Schreiber at the University of Chicago. Shepard and colleagues at Genentech (Paul Carter, Gail Lewis) then invented Herceptin, the first monoclonal antibody that blocks a cancer-causing protein, and developed it into a life-saving therapy for women with breast cancer. The innovation reduces the risk of recurrence and extends survival time for patients with metastatic as well as early-stage disease. Every year, more than 50,000 women in the US are diagnosed with the type of breast cancer that the drug attacks, and over 2.3 million individuals have received the treatment since it became available. Shepard and Ullrich (now at Max Planck Institute of Biochemistry, Martinsried, Germany) conducted their Herceptin investigations at Genentech. Slamon did his at the University of California, Los Angeles (UCLA). Shepard and Slamon, together with Dr. Robert Weinberg, were earlier honored by the Havard Medical School Warren Alpert Prize for research leading to the discovery of Herceptin.

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.

Sample publications:

The Team that Just Wouldn't Quit and a New Paradigm in Cancer Drug Discovery. Cell. 2019 Sep 19;179(1):27-32.

Biomarker-Driven Drug Discovery in Cancer-Trastuzumab Development: 2019 Lasker-DeBakey Clinical Medical Research Award.JAMA. 2019 Sep 10.

Breaching the Castle Walls: Hyaluronan Depletion as a Therapeutic Approach to Cancer Therapy Front Oncol. 2015; 5: 192.

A pan-HER approach for cancer therapy: background, current status and future development. Huang Z, Brdlik C, Jin P, Shepard HM. Expert Opin Biol Ther. 2009 Jan;9(1):97-110.

Inhibition of Cell Growth by NB1011 Requires High Thymidylate Synthase Levels and Correlates With p53, p21, Bax, and GADD45 Induction p53 Gene Therapy in a Rat Model of Hepatocellular Carcinoma: Intra-Arterial Delivery of a Recombinant Adenovirus Clin Cancer Res 1998 Jul;4(7):1649-59

Humanization of an anti-p185HER2 antibody for human cancer therapy. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, Rowland AM, Kotts C, Carver ME, Shepard HM. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4285-9.

Effects of growth factors on the antiproliferative activity of tumor necrosis factors. Sugarman BJ, Lewis GD, Eessalu TE, Aggarwal BB, Shepard HM. Cancer Res. 1987 Feb 1;47(3):780-6.

• 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