Dr. Joseph Frank Sambrook, a preeminent and internationally known molecular biologist involved in pioneering molecular cloning, died June 14 at 80. Dr. Sambrook was recruited to UT Southwestern in the 1980s as Chairman of Biochemistry and later served as Director of the Eugene McDermott Center for Human Growth and Development.

The native of England was a member of the National Institutes of Health’s Genome Research Review Committee. He proudly served as Chairman of the NIH/Department of Energy Advisory Committee on DNA Sequencing and led UT Southwestern researchers at the McDermott Center in a pivotal role in the Human Genome Project.

Later in his career, he was a leading breast cancer researcher in Australia. A Fellow of The Royal Society and of the Australian Academy of Science, he was an influential leader in the field of the molecular genetics of cancer, best known for his landmark studies on viral DNA and the molecular biology of normal and neoplastic cells. Among his many accomplishments, Dr. Sambrook was the senior author of the highly influential laboratory manual Molecular Cloning, co-authoring the third of four editions with Dr. David Russell, Vice Provost and Dean of Research, and Professor of Molecular Genetics at UTSW.

Joe Sambrook was an erudite and creative scientist who was a mentor, friend, and colleague to many at UT Southwestern. His significant contributions to science are an inspirational legacy, Dr. Russell said.

Dr. Sambrook studied at the University of Liverpool before obtaining his Ph.D. in 1966 at the Australian National University. He then conducted postdoctoral research at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England. (1966-1967) and the Salk Institute for Biological Studies in La Jolla, California (1967-1969).

In 1969, during his postdoctoral work at the Salk Institute, Dr. Sambrook met and impressed Dr. James Watson, co-discoverer of the structure of DNA and Director of the Cold Spring Harbor Laboratory.

I moved there with a three-year contract and stayed for the next 16 years, Dr. Sambrook recalled in a 2005 interview. “There were six people in the lab when I arrived; when I left there were more than 400.”

Dr. Sambrook and his Tumor Virus Group at Cold Spring Harbor Laboratory identified and mapped the major genes of adenoviruses and SV40, determined their transcriptional control in infected and transformed cells, and demonstrated the mechanism of integration of these viruses into the genome of the host cell.

Building on this work, Dr. Sambrook was one of the first to design viral vectors to express cloned genes in eukaryotic cells, which were used in a collaboration with his wife-to-be, Dr. Mary-Jane Gething, to express cloned influenza virus hemagglutinin and other membrane glycoproteins and to make important contributions to the understanding of intracellular traffic and protein folding. While still at Cold Spring Harbor Laboratory, Drs. Sambrook and Gething cloned the cDNA encoding the enzyme tissue-type plasminogen activator (tPA).

Dr. Sambrook’s seminal discoveries led Cold Spring Harbor to acknowledge his achievements with the dedication in 1985 of the Joseph F. Sambrook Laboratory.

Driven by the desire to translate research to medical application, Dr. Sambrook and Dr. Gething joined UT Southwestern in 1985, leading research to improve thrombolytic agents for dissolving blood clots. At the time, clinicians used tPA to dissolve coronary blood clots, but the treatment caused serious negative side effects including strokes and intracranial bleeding. Dr. Sambrook and Dr. Gething, together with graduate student Ed Madison and collaborators Dr. Elizabeth Goldsmith, Professor of Biophysics and Biochemistry, and Dr. Robert Gerard, devised and patented mutations in tPA that minimize the enzyme’s side effects and improve its therapeutic performance. This led to the design and synthesis of a new generation of tissue-type plasminogen activators that are still in clinical use today.

The Medical School was special, said Dr. Gething, who joined UT Southwestern as a Howard Hughes Medical Institute Investigator and Associate Professor of Biochemistry and served as Associate Dean of Southwestern Graduate School of Biomedical Sciences when UT Southwestern was known as the University of Texas Health Science Center at Dallas. At the time, she was the first investigator appointed to the HHMI on the UTHSCD campus. In many medical schools around the United States, there were very much at that time – and possibly still – deep divisions between the basic researchers and the clinicians. But in Dallas, right from the beginning, Dr. Donald Seldin had insisted that his clinicians have a research focus. So, there was this amazing synergy at UT Southwestern between the clinicians and the basic scientists. Dr. Jim Willerson, who was leading Cardiology at the time, was a perfect paradigm for this. The first day that we started work at UT Southwestern, Jim came over and said, ‘You know I need to put clinical fellows from cardiology into your lab. They need to know molecular biology.’ And so, for us it made the tPA project so much more important than just the beauty of the science.

At UT Southwestern, Dr. Sambrook held The Sam G. Winstead and F. Andrew Bell Distinguished Chair in Biochemistry, was the Peter J. O’Donnell Distinguished Professor of Molecular Biology, and was Director of the Bugher Center for Molecular Cardiology. He stepped down as Chairman of Biochemistry at UT Southwestern in 1991 to lead the Eugene McDermott Center for Human Growth and Development.

In late 1994, Dr. Sambrook returned to Australia to join the Peter MacCallum Cancer Centre in Melbourne as Director of Research. The move gave Dr. Sambrook the opportunity to start new research programs, including founding and directing the Kathleen Cunningham Foundation Consortium for research into Familial Breast cancer (kConFab). He was one of two founding directors of Cancer 2015, a multiyear, large-scale program funded by the Victorian government on personalized treatment of cancer.

Dr. Sambrook’s honors include election as a Fellow of The Royal Society in 1985 and of the Australian Academy of Science in 2000, appointment as a Distinguished Fellow of the Peter MacCallum Cancer Centre also in 2000, and recognition by the Victorian Government Leadership and Innovation Award in 2009. He was awarded honorary doctorates by the University of Liverpool in 2007 and the Watson School of Biological Sciences in 2008.