Lasker-DeBakey Clinical Medical Research Award Research Articles

Chemistry Matters—From a Putative Peptide to Effective Treatments for Diabetes and Obesity

In this Viewpoint, 2024 Lasker-DeBakey Clinical Medical Research Award winner Svetlana Mojsov describes her discovery of GLP-1 (7-37), the biologically active incretin that led to development of effective GLP-1 analogues for treating diabetes and obesity.

GLP-1 for Treating Obesity—Origin, History, and Evolution

In this Viewpoint, 2024 Lasker-DeBakey Clinical Medical Research Award winner Lotte Bjerre Knudsen describes her discovery of glucagon-like peptide-1 for the treatment of patients with obesity.

Optical Coherence Tomography—History, Evolution, and Future Prospects

In this Viewpoint, 2023 Lasker-DeBakey Clinical Medical Research Award winners James G. Fujimoto, David Huang, and Eric A. Swanson discuss their invention—optical coherence tomography, which allows rapid detection of diseases of the retina that impair vision.

Seeing is believing: The development of optical coherence tomography

The 2023 Lasker-DeBakey Clinical Medical Research Award is being presented to James Fujimoto, David Huang, and Eric Swanson for their invention and development of optical coherence tomography (OCT), an imaging technology that uses light to visualize microscopic structures within tissues such as the retina. OCT has dramatically changed the practice of ophthalmology and improved the lives of millions of people. It also has great potential in a wide range of other medical fields.

Before you call the midwife.

The 2022 Lasker-DeBakey Clinical Medical Research Award is presented to Yuk Ming Dennis Lo of the Chinese University of Hong Kong for the discovery of fetal DNA in maternal blood, leading to development of noninvasive prenatal testing for Down syndrome.

Discovery of Cell-Free Fetal DNA in Maternal Blood and Development of Noninvasive Prenatal Testing

In this Viewpoint, 2022 Lasker-DeBakey Clinical Medical Research Award winner Y. M. Dennis Lo discusses his discovery and application of cell-free fetal DNA for noninvasive prenatal testing.

First person profile: Dennis J. Slamon, MD, PhD: Dr. Slamon's pioneering work helped lead to the breakthrough breast cancer drug trastuzumab, which has saved and extended the lives of millions of patients.

First person profile: Dennis J. Slamon, MD, PhD: Dr. Slamon's pioneering work helped lead to the breakthrough breast cancer drug trastuzumab, which has saved and extended the lives of millions of patients.

Immune System Research Underlies Lasker Awards

The Albert and Mary Lasker Foundation bestowed two awards on five scientists for their groundbreaking research. Max D. Cooper, MD, of the Emory University School of Medicine in Atlanta, GA, and Jacques Miller, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia, received the 2019 Albert Lasker Basic Medical Research Award for identifying the two classes of lymphocytes, B cells and T cells. H. Michael Shepard, PhD, formerly of Genentech; Dennis J. Slamon, MD, of the University of California, Los Angeles; and Axel Ullrich, PhD, of the Max Planck Institute of Biochemistry in Martinsried, Germany-shared the 2019 Lasker-DeBakey Clinical Medical Research Award for developing the first mAb, trastuzumab.

Moving from Cancer Genetics to Therapy.

Dennis Slamon's early interest in understanding genes that viruses co-opt to become powerful proliferative agents ultimately led him and his colleagues and collaborators to the development of trastuzumab (Herceptin) for the treatment of HER-2-positive breast cancer. His work set the stage for current "givens" like genetic stratification of patients for treatment and using antibodies as therapeutics. Cell editor Lara Szewczak spoke with Dennis, the recipient of the 2019 Lasker-DeBakey Clinical Medical Research Award, to discuss the research leading to trastuzumab and his views on how current progress in treating cancers may impact the US health care system. Excerpts from this conversation are presented below, and the full conversation is available with the article online.

Great achievements from hard working and perseverance: propofol developer winning the Lasker-Debakey Clinical Medical Research Award

Great achievements from hard working and perseverance: propofol developer winning the Lasker-Debakey Clinical Medical Research Award

Abstract CN03-01: Systematic elucidation and pharmacologic targeting of mechanistic tumor dependencies

Abstract Cancer targets fall into three categories: oncoproteins eliciting tumor-specific essentiality due to their direct role in tumorigenesis or tumor maintenance (oncogene dependency) (1), proteins eliciting synthetic lethality with oncogene mutations but having no direct impact on tumorigenesis (non-oncogene codependency) (2), and proteins modulating immunosurveillance (immune-checkpoint dependency) (3). Despite undeniable successes, only 5-11% of cancer patients treated with mutation-based targeted therapy derive objective benefit, based on progression-free survival (4, 5). While immuno-oncology holds great promise, its applicability is also limited by partial efficacy, relapse, and toxicity. As a result, the majority of tumors that are not completely removed by surgery still fail to respond to therapy or relapse to drug-resistant disease. To complement these canonical approaches, we will leverage a framework for the network-based identification and pharmacologic targeting of tumor dependencies implemented by master regulator (MR) proteins, which was developed over the last 8 years by the CTD2 Center at Columbia University. These studies have shown that aberrant activity of a handful of MR proteins—within one or more tumor checkpoint modules (TCM) —is necessary for the stability of cancer phenotypes (6). As a result, genetic or pharmacologic inhibition of individual or synergistic MRs can induce TCM collapse and abrogate tumor viability in a wide range of human malignancies. Specifically, we propose that such a TCM/MR-based framework provides a systematic, mechanistic, and highly efficient platform to elucidate new druggable targets for single-agent and combination therapy, as well as effective molecular biomarkers for patient sensitivity, across most tumor types. The therapeutic strategies prioritized by the proposed framework, on an individual tumor basis, will be rapidly tested in PDX models (N of 1 methodology), leading to rapid identification of candidate drugs and combinations for potential follow-up clinical validation (e.g., in basket trials) (7), consistent with the translational track record of our CTD2 Center (6, 8). We will specifically target malignancies that are either rare and thus poorly characterized, such as atypical/anaplastic meningioma (MEN), or considered untreatable, such as metastatic bladder (BLCA), lung (LUAD), and colon (COAD) adenocarcinoma.

One 2016 Nobel: Yeast-Based Autophagy Work; 3 MacArthurs: Microbiology

The 2016 Nobel Prize in Physiology or Medicine, about $936,000 this year, recognizes Yoshinori Ohsumi of Japan for his efforts to understand autophagy, a fundamental process for degrading and recycling cellular components, research that he began by studying yeast. Separately, among the 2016 MacArthur Foundation Fellows, who receive $625,000 “genius awards,” are microbiologist Dianne Newman, who studies bacteria that played roles in shaping the Earth as well as in modern biomedical contexts; geobiologist Victoria Orphan, whose focus is on microbial communities in extreme environments; and physical biologist Manu Prakash, who invented several devices that can be used for diagnostic work in microbiology. Also noteworthy, the 2016 LaskerDeBakey Clinical Medical Research Award is shared by three scientists whose research on hepatitis C virus (HCV) led to development of drugs for treating HCV infections.

Profile of Charles M. Rice, Ralf F. W. Bartenschlager, and Michael J. Sofia, 2016 Lasker–DeBakey Clinical Medical Research Awardees

Hepatitis C: From chronic to curable Three researchers, Ralf F. W. Bartenschlager (University of Heidelberg), Charles M. Rice (The Rockefeller University), and Michael J. Sofia (Arbutus Biopharma, Inc.) (Fig. 1) share the 2016 Lasker–DeBakey Clinical Medical Research Award for their work, which has allowed for the development of a therapeutic drug against chronic hepatitis C. Finding a cure against this dreadful disease represents a major medical breakthrough, the importance of which cannot be overstated. Fig. 1. Ralf F. W. Bartenschlager, Charles M. Rice, and Michael J. Sofia, pictured in order above, shared the 2016 Lasker–DeBakey Clinical Medical Research Award for their work on hepatitis C. Images courtesy of the Albert and Mary Lasker Foundation. Hepatitis viruses, as the name implies, infect the liver and can be associated with a variety of illnesses. Hepatitis A viruses lead to a self-limited disease, which can be seriously debilitating for months. Hepatitis B viruses can cause an acute, short-term illness, but can also be associated with long-term chronic infection resulting in cirrhosis or liver cancer. Both hepatitis A and hepatitis B vaccines are highly efficacious and have been available for decades in the United States. Consequently, hepatitis A and hepatitis B are both preventable diseases. What is different about hepatitis C? Critically, there is no vaccine available against this disease. Unfortunately, an estimated 170 million people are chronically infected with hepatitis C virus and ∼350,000 lives are lost every year worldwide (1). These high numbers are comparable to the morbidity and mortality of other viral diseases, such as HIV and influenza. The WHO estimates that more than a million people die annually of AIDS-related illnesses and up to half a million people succumb to influenza globally every year (2, 3). The common trait shared by these top three viral diseases, hepatitis C, AIDS, and influenza, … [↵][1]1Email: peter.palese{at}mssm.edu. [1]: #xref-corresp-1-1

Cancer Immunotherapy Researchers Focus on Refining Checkpoint Blockade Therapies

The origins of cancer immunotherapy date back more than 2 decades to when researchers explored ways to amplify the immune system to attack tumor cells. At the time, scientists hypothesized that tumors were able to evade immune survei l lance because tumor cells lacked costimulatory molecules required to signal T cells to the presence of the tumor. However, in the mid-1990s, James P. Allison, PhD, and his colleagues at the University of California, Berkeley, Cancer Research Laboratory discovered that rather than lack costimulatory molecules, tumor cel ls and other immune cel ls expressed inhibitory molecules that disabled T cells from recognizing and eliminating tumors. These early experiments compared tumor growth in mice that had received injections of cytotoxic T lymphocyte– associated molecule 4 (CTLA-4) antibodies with tumor growth in mice in a control group (Leach DR et al. Science. 1996;271: 1734-1736). Allison and his colleagues hypothesized that the antibodies would turn off CTLA-4, a receptor that dampens T-cell activity, and thus unleash an attack on the tumors. The experiment results were striking. “The idea was that the brakes come on at a certain point. If we just disabled the brakes, [the immune system] can keep going until it has time to kill the tumor mass. In the first experiment, in the control group, all the mice had to be euthanized because they grew big tumors. In the [treated] mice, the tumors had gone away,” recalled Allison, who at the time was director of the Cancer Research Laboratory. But when the data were published in Science in 1996, the response from the research community was more like a collective shrug than a buzz of excitement, recalled Allison, now the executive director of the Immunology Platform and chair of the department of immunology at the MD Anderson Cancer Center in Houston. “Cancer immunotherapy had a checkeredhistory,”he said, noting thatdisillusionment had set in among researchers after interleukin-2 and cancer vaccines failed to meet high expectations for their success. Despite the initial muted response to his work, and nearly 2 decades after the publication in Science, Allison received both the 2015 Lasker-DeBakey Clinical Medical Research Award and the 2015 American Society of Clinical Oncology’s Science of Oncology Award for his work that contributed to the development of cancer immunotherapy. Now, dozens of clinical trials are under way to study how these drugs work on several different types of cancers, and oncology researchers are trying to determine why these drugs are lifesavers for some patients but fail to help others.

Timeline: Checkpoint Blockade

Immune checkpoint therapy, targeting inhibitory pathways in T cells to unleash antitumor immune responses, has led to amazing advances in the clinical care of patients with highly aggressive and otherwise-untreatable cancers. Paraphrasing Jim Allison, the recipient of the 2015 Lasker-DeBakey Clinical Medical Research Award, before we were able to successfully use the immune system to treat cancer, we had to understand the inner workings of the immune response. This timeline highlights key contributions over the past 30 years that constituted essential steps toward the concept of immune checkpoint therapy.

2014 Lasker-DeBakey Clinical Medical Research Award.

2014 Lasker-DeBakey Clinical Medical Research Award.

The Lasker-DeBakey Clinical Medical Research Award.

The Lasker-DeBakey Clinical Medical Research Award.

Parkinson's disease in the limelight.

The 2014 Lasker-DeBakey Clinical Medical Research Award -one of three prestigious awards granted by the Lasker Foundation in recognition of scientists, clinicians and public servants who have made major advances in the understanding, diagnosis, treatment, cure or prevention of human disease- has been granted to two pioneers in the field of Parkinson's disease therapy. In spite of the availability of more than two dozen drugs and fixed-dose combination products to treat the symptoms of Parkinson's disease -most notably the gold standard levodopa, a dopamine precursor- as well as nonpharmacological treatments like deep brain stimulation, many patients do not respond to available drugs or experience breakthrough symptoms, and the disease is ultimately uncurable. This article reviews currently available therapies as well as biomarkers and novel diagnostics.

The Evolving Science of Cochlear Implants

Graeme M. Clark and colleagues describe the evolving science of cochlear implants and the histopathology associated with a patient who had his implant removed when it failed in 1983 and again in 1998. Dr Clark has been awarded the 2013 Lasker-DeBakey Clinical Medical Research Award for his pioneering work in cochlear implant development. In 1978, the first multichannel cochlear implant was developed in Australia and a prototype was surgically implanted in a 48-year-old patient (MC-1). After a series of clinical trials, the US Food and Drug Administration approved the use of the Australian cochlear implant in adults in 1985, and subsequently, the agency has approved the device for use in infants as young as 6 months of age. During the past 3 decades, more than 300 000 patients have had their hearing restored with cochlear implants. In this Viewpoint, we describe how the assessment of the temporal bone of MC-1, the first patient to receive a cochlear implant, is aiding the further development of the device.

Liver Transplantation: From Inception to Clinical Practice

The 2012 Lasker-DeBakey Clinical Medical Research Award will be conferred on Thomas Starzl of the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania, USA and Roy Calne of the University of Cambridge in Cambridge, UK. They are recognized for pioneering the development of liver transplantation, an intervention that saves 20,000 lives world-wide each year.