Team Archive - Page 4 of 6 - NFCR

Team

Daniel A. Haber, M.D., Ph.D.

Massachusetts General Hospital Cancer Center

Boston, Massachusetts
Director, Massachusetts General Hospital Cancer Center
Professor of Oncology,  Harvard Medical School

Research

Dr. Daniel A. Haber’s laboratory focuses on understanding the genetic abnormalities of cancer – from inherited mutations (with familial predisposition) to mutations that are acquired by tumors themselves – and the research aims to guide targeted drug therapies.

Circulating tumor cells (CTCs) are tumor cells that have become detached from the primary tumor and enter blood circulation. Although rare, these cancer cells hold the key to understanding the process of cancer metastasis. Dr. Haber and his collaborators developed the CTC-iChip — an advanced micro-engineered device that captures these rare CTCs from the blood. Genetic testing on captured CTCs may give doctors a way to more effectively treat the tumor or stop it from spreading. Moreover, CTCs allow the response of treatments to be monitored in real time. The device could dramatically improve treatment and diagnosis for many different types of metastatic cancers, including metastatic breast cancer.

Recently, Dr. Haber and his team made another discovery – this time regarding cancer drug resistance. They found that cultured CTCs from women with advanced breast cancer can switch on and off the expression of a key tumor promoting gene HER2, which makes them resistant to many drugs. The research suggests that drugs combatting both gene expression states should be delivered simultaneously to effectively treat advanced breast cancer.

Dr. Haber’s work extends beyond breast cancer research. His lab is responsible for identifying a specific mutation in the epidermal growth factor receptor (EGFR) in a subset of non-small cell lung cancer (NSCLC). By linking EGFR mutations to lung cancer, Dr. Haber made it possible to identify patients who will respond well to certain cancer-fighting drugs that block EGFR mutations. In July 2015, the FDA approved the drug Iressa® as a front-line treatment for patients with these specific tumor mutations that Dr. Haber identified.

The team is now developing technology to enable laboratory cultures of CTCs from patients with metastatic lung cancer, melanoma and other types of cancer.  Success in this endeavor would open a new path toward predictive drug sensitivity and allow doctors to prescribe the most effective individualized regimen from the outset of treatment.

Bio

Daniel A. Haber, M.D., Ph.D., is the Director of the Massachusetts General Hospital (MGH) Cancer Center and a professor of oncology at Harvard Medical School. He received his Bachelor and Master degrees from the Massachusetts Institute of Technology (MIT), and received a M.D. and Ph.D. from Stanford University School of Medicine. Following his schooling, Dr. Haber conducted his postdoctoral training at MIT and joined the Harvard Medical School faculty in 1991 as an assistant professor.

Dr. Haber is most interested in the area of cancer genomics, including the study of circulating tumor cells, the Wilms tumor and genetic predisposition to breast cancer.

In addition to his award with NFCR, Dr. Haber is an elected member of the National Academy of Medicine, a fellow of the American Academy of Arts and Sciences, on the Board of Directors for the American Association for Cancer Research and a member of the Association of American Physicians and the American Society for Clinical Investigation. He is also on the editorial boards of Cell and Cancer Cell, and has served as genetics editor for the New England Journal of Medicine.

Dr. Haber has been honored with a MERIT Award from the National Cancer Institute, the Emil Freireich Award from MD Anderson Cancer Center, Stand Up to Cancer Dream Team Award, a Dream Team Award from the Prostate Cancer Foundation, the Sternlicht Award from Case Western Reserve and the Hinda Rosenthal Award for Translational Research from the American Association for Cancer Research.

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Susan B. Horwitz, Ph.D.

Albert Einstein College of Medicine

New York, New York
Distinguished Professor, Department of Molecular Pharmacology
Rose C. Falkenstein Chair in Cancer Research

Research

Triple negative breast cancer (TNBC) comprises approximately 15-20% of all breast cancers. The aggressive TNBC tumors are treated with chemotherapy drugs such as Taxol®, but some patients with specific types of TNBC do not respond to their drugs outright or relapse after remission.

Dr. Horwitz is a molecular pharmacologist who studies how drugs work in the body. She is the scientist who discovered how Taxol works inside cells to halt cell division. Finding new anti-cancer treatments and approaches to stop resistance is Dr. Horwitz’ scientific passion.

Dr. Horwitz is collaborating with other scientists, including NFCR-funded scientist Dr. Amos B. Smith, III to develop new drugs to overcome the drug resistance problem. The new drugs are hybrid molecules containing active segments of Taxol and another drug called discodermolide. These hybrid molecules will have an increased affinity to the cancer targets and reduced risk of drug resistance as well as toxicity. Two candidate molecules have been identified and tested, and the results were very promising. These candidate molecules will be further tested to evaluate their efficacy and toxicity on complex tumor models.  Besides breast cancer, Taxol is also widely used for treating patients with ovarian and lung cancer.  The new hybrid molecules developed by Drs. Horwitz and Smith may help improve treatment of these cancers as well.

In addition to the hybrid drug research, Dr. Horwitz’s team is making significant strides in their Taxol drug resistance research. The beta tubulin protein is Taxol’s cellular target that Dr. Horwitz discovered. It’s a complicated protein because there are eight different tubulin subtypes and Dr. Horwitz found the response or resistance to Taxol may depend on these subtypes. Her team recently obtained sufficient amounts of one of these subtypes – beta-III tubulin – and were able to show, for the first time, that Taxol binds less to this tubulin type and that it may contribute to drug resistance. The researchers are now isolating adequate amounts of all tubulin subtypes, following the methodology used for beta-III tubulin, to determine how Taxol interacts with each one individually. These results may help predict which patients would respond to Taxol and the patients that would not respond well could be spared unpleasant side effects.

Bio

Susan Band Horwitz, Ph.D., is a Distinguished Professor at the Albert Einstein College of Medicine. She is also the co-chair of the Department of Molecular Pharmacology and the Rose C. Falkenstein Chair in Cancer Research.

Dr. Horwitz grew up in Boston, went to Bryn Mawr College and received her Ph.D. in Biochemistry from Brandeis University. Dr. Horwitz worked as a postdoctoral fellow at Tufts University’s Medical School and at Emory University’s School of Medicine. In 1967, she began work at the Albert Einstein College of Medicine.

Dr. Horwitz’s key interest is finding cancer treatments using natural products as a source for new drugs.

Over the course of her career, Dr. Horwitz’s work has been published over 250 times, and she has been awarded the C. Chester Stock Award from Memorial Sloan Kettering Cancer Center, the Warren Alpert Foundation Prize from Harvard Medical School, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the American Cancer Society’s Medal of Honor and the AACR Award for Lifetime Achievement in Cancer Research.

Areas of Focus

Cancer Types

Years of NFCR Funding

2000 – Present

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Laurence Hurley, Ph.D.

University of Arizona

Phoenix, Arizona
Howard J. Schaeffer Endowed Chair in Pharmaceutical Sciences, University of Arizona
Professor, University of Arizona’s College of Pharmacy
Co-Director, Molecular Therapeutics Program, University of Arizona’s Cancer Center
Associate Director, BIO5 Institute

Research

Dr. Hurley’s current research focuses on the design and development of anti-tumor agents.

Throughout the past 20 years, Dr. Hurley’s laboratory has found seven different groups of compounds that may be useful in the treatment of cancer. The studies have been used in the biopharmaceutical industry to develop several drugs that were evaluated in clinical trials. Quarfloxin, for example – which was discovered and developed by Dr. Hurley – is the first-in-class G-quadruplex-interactive molecule that reached phase II clinical trials.

At the NFCR Center for Targeted Cancer Therapies (2001– 2017), Co-Directors Dr. Hurley and Dr. Daniel Von Hoff worked together on a genetic structure-based approach to drug design. They combine Dr. Hurley’s medicinal chemistry research with Dr. Von Hoff’s clinical oncology program in cancer therapeutics.

The team has identified, designed and synthesized multiple new compounds that selectively kill pancreatic cancer cells with mutations in the cancer-causing K-ras gene—which are present in more than 90% of pancreatic tumors. The leading compounds are being further developed for possible clinical translation.

With Dr. Hurley’s expertise in G-quadruplex-interactive molecules, the team at the Center has also worked on an entirely new approach to treating cancer by developing G-quadruplex drugs that block newly-recognized genetic structures called “super enhancers.” These large clusters of DNA regulatory elements control the expression of a host of genes — including the critical cancer gene c-Myc – and offer a great opportunity for cancer disruption. This new approach may lead to great improved treatments for lung cancer- in particular small-cell type, pancreatic cancer, lymphoma, multiple myeloma, colorectal and other cancers.

Bio

Laurence Hurley, Ph.D., was born in Birmingham, England and he received his Bachelor of Pharmacy from Bath University. He then received his Ph.D. from Purdue University and conducted his postdoctoral research at the University of British Columbia. He has served on the faculties at the University of Maryland, the University of Kentucky and the University of Texas at Austin. In 2000, Dr. Hurley joined the University of Arizona (UA) as the Howard J. Schaeffer Chair in Pharmaceutical Sciences and he has served as the Associate Director of the BIO5 Collaborative Research Institute and Co-Director of the Molecular Therapeutics Program at the Arizona Cancer Center as well. While at UA, he has trained more than 40 graduate and post-doctoral students. A prolific author and inventor, Dr. Hurley has published 270 peer-reviewed articles and 25 issued patents or patent applications. He has placed two novel cancer medicines into human clinical trials.

Dr. Hurley is the scientific founder of Cylene Pharmaceuticals, where the Quarfloxin molecule was discovered and developed. He is also the scientific founder and CEO of TetraGene, a biotech company that focuses on targeting secondary DNA structures. He is the founder and CSO of Reglagene, the biotech company focusing on the discovery of small molecule drugs that selectively interact with quadruplexes to regulate gene expression. Additionally, Dr. Hurley has been a consultant to pharmaceutical companies throughout his career.

From 1992 to 2010, Dr. Hurley was a senior editor of the Journal of Medicinal Chemistry and, from 2008 to 2012, he was a member and then chair of the National Cancer Institute’s Scientific Board of Councilors. He is the recipient of various lectureships, including the 2001 Frank Rose Memorial Lecture at the British Association for Cancer Research, the 1999 Prestige Lectureship at Bradford University, the 2007 Mary E. Kapp Lecturer in Chemistry at the Virginia Commonwealth University and the 2012 Hecht Lecturer at the University of Virginia. In 1996, he was awarded a Doctor of Science degree from his alma mater, Bath University.

Dr. Hurley received the 1988 George Hitchings Award in Innovative Methods in Drug Design, the 1989 Volwiler Research Achievement Award from the American Association of Colleges of Pharmacy, the 1992 American Pharmacists Association Research Achievement Award in Medicinal Chemistry, the 1994 National Cancer Institute’s Outstanding Investigator Award, the 1994 American Chemical Society Medicinal Chemistry Award and the 2005 George and Christine Sosnovsky Award in Cancer Therapy from the Royal Society of Chemistry. In 2007, Dr. Hurley was inducted into the American Chemical Society’s Medicinal Chemistry Hall of Fame and was named Innovator of the Year by the University of Arizona. Subsequently, Dr. Hurley received the 2008 American Association of Colleges of Pharmacy’s Paul R. Dawson Biotechnology Award and the 2011 Nucleic Acids Award by the Royal Society for Chemistry.

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Rakesh K. Jain, Ph.D.

Massachusetts General Hospital

Boston, MA 
Andrew Werk Cook Professor of Tumor Biology, Harvard Medical School
Director of the Edwin L. Steele Laboratory for Tumor Biology, Massachusetts General Hospital

Research

Dr. Jain is a leader in the field of tumor biology – specifically in anti-angiogenic therapy, which looks at thwarting certain types of blood vessel formation.

His seminal research demonstrated that anti-angiogenic therapy works by normalizing the abnormal, leaky blood vessels that usually surround and penetrate tumors. This therapy improves the delivery of chemotherapy drugs, increases the oxygen content of cancer cells and makes radiation treatments more effective.

Dr. Jain has been studying the role angiogenesis plays in glioblastoma multiforme (GBM), the deadliest form of brain cancer. Dr. Jain’s research is helping doctors better tailor the use of anti-angiogenic therapies by identifying the characteristics that cause resistance to anti-angiogenic therapy for GBM patients. Dr. Jain and his team have identified molecular resistance pathways that may direct the development of new drugs that target these pathways and could extend the benefits of anti-angiogenic therapies for patients.

Because GBM invades healthy tissues near the tumor, Dr. Jain is currently testing inhibitors that could prevent invasion. Vessel co-option is a process by which cancer cells migrate through and around nearby healthy tissue.  Dr. Jain is identifying genes and pathways that facilitate vessel co-option in order to prevent invasion and improve GBM therapies.

Bio

Rakesh Jain, Ph.D., moved from his home in India to the United States in 1972 after receiving a B. Tech in Chemical Engineering from the Indian Institute of Technology. He then attended the University of Delaware, where he completed a M.S. and Ph.D. in chemical engineering. Dr. Jain served on the faculty of Columbia University for two years and spent 14 years at Carnegie Mellon University. Since 1991, Dr. Jain has been the Andrew Werk Cook Professor of Tumor Biology and the Director of the Edwin L. Steele Laboratory for Tumor Biology at Massachusetts General Hospital.

In addition to his fellowship with NFCR, Dr. Jain has appointments with the National Academy of Sciences, the National Academy of Engineering and the National Academy of Medicine. He is the ninth person ever to be elected to all three U.S. National Academies.

Throughout his career, Dr. Jain has also been the recipient of numerous prestigious awards, including the 2012 Science of Oncology Award from the Society of Clinical Oncology and the 2016 National Medal of Science from President of the United States Barack Obama. He received the Medal of Science for developing new ways to manipulate tumors.

Dr. Jain has mentored more than 200 doctoral and postdoctoral fellows in more than a dozen disciplines. He has also collaborated with hundreds of basic scientists in fundamental research and physicians across multiple specialties and the partnerships have resulted in more than 500 publications.

Areas of Focus

Cancer Types

Years of NFCR Funding

1998 – Present

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Brian Leyland-Jones, M.B., B.S., Ph.D.

Avera Cancer Institute

Sioux Falls, South Dakota
Vice President of Molecular and Experimental Research, Avera Cancer Institute
Director, The Darwin Foundation

Research

Dr. Leyland-Jones is best known for leading major changes in breast cancer clinical trials and treatments, as well as his ongoing focus on how genomics plays a vital role in the fight against breast cancer.

When conducting genomics research and developing personalized treatments for cancer patients, biomarkers are key. Because these distinct biological indicators are so important, there is a growing and urgent need for biomarker profiling and validation in the cancer research community. As the Director of the Darwin Foundation (formerly the Consortium for Clinical Diagnostics), Dr. Leyland-Jones is partnering with scientists at research institutions and biopharmaceutical companies who are dedicated to facilitating genomic research and diagnostics. The Darwin Foundation provides a centralized infrastructure where disease genes and genetic signatures can be identified and validated. The Darwin Foundation also develops medical response tests, as well as new and improved diagnostic tests for a variety of diseases, including cancers.

Throughout his career, Dr. Leyland-Jones helped develop drugs that are now mainstays of oncologic breast cancer treatment (such as the anthracycline, antimetabolite and platin families), as well as the targeted therapies trastuzumab (Herceptin®) and bevacizumab (Avastin®). He also helped disprove some theories about how to best treat breast cancer patients. For example, he demonstrated that two years of adjuvant trastuzumab was no better than the standard one year of treatment for women with HER2-positive, early-stage breast cancer.
Additionally, Dr. Leyland-Jones helped drive global collaboration and material collections as a member of the Executive Steering Committee of the Tissue Bank Consortium in Asia that was founded and operated by NFCR.

Bio

Brian Leyland-Jones, M.B., B.S., Ph.D., received biochemistry, medical and doctoral degrees from the University of London and completed his residency at Hammersmith, Brompton, St. Bartholomew’s and London hospitals. He then conducted fellowships at Cornell University and Memorial Sloan-Kettering Cancer Center. He became part of Sloan-Kettering’s medical staff, researching new anti-cancer compounds.

From 1983-1990, Dr. Leyland-Jones served at the National Cancer Institute as head of Developmental Chemotherapy and he oversaw the development of approximately 70 anti-cancer compounds. From 1990-2000, he was the director of the McGill University Comprehensive Cancer Centre and the founding chair of Oncology. Dr. Leyland-Jones also served as a professor of medicine at McGill University. From 2007-2012, he was the Director of the Winship Cancer Institute at Emory University, as well as a Professor of Medicine and Associate Vice-President of Health Sciences.

Dr. Leyland-Jones has also worked in the private sector. He became Founding Chairman and Chief Executive Officer of Xanthus (a biotech company focused on individualized cancer therapies in 2001), and he has been the Director of Genta, Inc. since April 2012. Dr. Leyland-Jones is also a member of the Scientific and Clinical Advisory Boards at Welichem Biotech Inc. and Antigen Express Inc.

Currently, Dr. Leyland-Jones is the Vice President of Molecular and Experimental Research at the Avera Cancer Institute and the Director of the Darwin Foundation. Dr. Leyland-Jones has held leadership positions in many large medical organizations, including the Eastern Cooperative Oncology Group, the Tissue Bank Consortium in Asia (that was founded and operated by NFCR), the Cancer and Leukemia Group B, the International Breast Cancer Study Group, the National Cancer Institute of Canada and Breast International Group. He is also the Director of the Darwin Foundation (formerly the Consortium for Clinical Diagnostics) that provides a centralized infrastructure where disease genes and genetic signatures can be identified and validated.

He has received many awards and honors throughout his career, including the Vivian Saykaly Visiting Professor Award by the Cedars Cancer Institute in Montreal and being named an Eminent Scholar by the Georgia Research Alliance and a Distinguished Cancer Scholar by the Georgia Cancer Coalition.

Throughout his career, Dr. Leyland-Jones has written more than 180 peer-reviewed articles and book contributions, and he holds 34 patents.

Dr. Leyland-Jones has mentioned that a quote from one of the co-founders of NFCR, Dr. Albert Szent Györgyi, is particularly meaningful to him in regards to cancer research. Dr. Szent Györgyi said: “Discovery consists in seeing what everyone else has seen and thinking what no one else has thought.”

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Wayne Marasco, M.D., Ph.D.

Dana-Farber Cancer Institute
Harvard Medical School

Boston, Massachusetts
Professor, Department of Cancer Immunology at the Dana-Farber Cancer Institute
Professor of Medicine, Department of Medicine at Harvard Medical School

Research

Dr. Wayne Marasco is a world-renowned antibody engineering expert who works on infectious diseases and cancer immunotherapies. Dr. Marasco’s laboratory has developed one of the largest human antibody phage display libraries ever made (with tens of billions of members).

For cancer, as well as HIV/AIDS and other infectious diseases, one possible treatment involves the use of human monoclonal antibodies (Mabs) – which are proteins that are produced to bind to only one substance. For cancer treatments, Mabs bind only to cancer cells and produce immunological responses against the cancer cells. There is great promise with Mabs because their tumor-fighting effects would be less harmful to normal cells than that of traditional cancer treatments.

In an effort to greatly expand the use of Mabs in the treatment of cancer, Dr. Marasco and NFCR founded the NFCR Center for Therapeutic Antibody Engineering. He collaborates with accomplished global cancer investigators in a joint effort to uncover new Mabs using his laboratory’s human antibody library.

Dr. Marasco has had great success developing Mabs that attach to an important protein – carbonic anhydrase IX (CAIX) – that is highly expressed in renal cell carcinoma, the most common type of kidney cancer. Once attached, the CAIX antibody can halt abnormal cancer growth.

Most recently, his team at the NFCR Center developed a combination immunotherapy treatment that holds promise for treating metastatic kidney cancer more effectively. The immunotherapy they have engineered includes not only the CAIX antibody that detects and binds to CAIX growth-promoting proteins on cancerous kidney cells, but also unblocks T cells to enable more rigorous attacks against cancer. Moreover, this double treatment approach could be adapted to treat advanced colon, breast, brain and other difficult-to-treat solid cancers using different antibodies.

Bio

Wayne Marasco, M.D., Ph.D., studied at the University of Connecticut’s School of Medicine, where he received his Ph.D. in 1980. He conducted his postdoctoral training at the University of Michigan Medical School, where he also earned a M.D. in 1986. He received his sub-specialty training in infectious diseases at Harvard Medical School, where he is currently a professor, and he joined the Dana-Farber Cancer Institute in 1989. In 1992, he also joined the Division of Infectious Diseases at Brigham and Women’s Hospital.

In 1980 and 1981, Dr. Marasco won the Biomedical Research Council Award and the National Research Service Award from the University of Connecticut School of Medicine, and the University of Michigan awarded him the United States Public Health Service Award in 1981, the Dean’s Award for Research Excellence in 1986 and the Lung Immunopathology Training Grant Award in 1987 and 1988.

In 2003, Dr. Marasco became the Director of the NFCR Center for Therapeutic Antibody Engineering to expand the use of human monoclonal antibodies in the treatment of cancer. In 2009, U.S. News & World Report listed Dr. Marasco as a “Medical Pioneer” and a top scientist in his field. In the same year, Dr. Marasco was selected as a Distinguished Speaker by the Walter Reed Army Institute of Research.

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Paul Schimmel, Ph.D.

The Scripps Research Institute

San Diego, California
Ernest and Jean Hahn Professor at the Skaggs Institute for Chemical Biology, The Scripps Research Institute

Research

Click here to read about Dr. Schimmel’s latest published work supported by NFCR

One of the most fundamental questions facing scientists today is how seemingly normal cells become cancerous. To better understand how this happens, Dr. Paul Schimmel has dedicated more than 40 years to examining the minute forms and intricate functions of molecular biology.

In 1983, Dr. Schimmel developed the concept for what are now known as ESTs (expressed sequence tags) and the strategy of shotgun sequencing. These approaches were later adopted in the human genome project. In fact, his work on the development of ESTs is known as one of the four key developments that launched the human genome project.

Throughout his career, Dr. Schimmel has been one of the few scientists studying both nucleic acids and proteins. His laboratory identified the operational RNA code for amino acids – known as aminoacyl tRNA synthetases – which are believed to be among the first enzymes in the early stages of evolution. These enzymes are essential for all forms of life and establish the rules of genetic code.

The Schimmel laboratory also forged a link between protein synthesis and signal transduction pathways in human cells. In particular, they demonstrated that a human tRNA synthetase could be split into two distinct substances. In subsequent studies, they established how specific human tRNA synthetases play a role in blood vessel formation – called angiogenesis. This work has led to efforts to develop tRNA synthetases to treat diseases such as macular degeneration and cancers.

In 2013, Dr. Schimmel’s team discovered that one type of tRNA – TyrRS – plays an important role in platelet production and maintenance. Platelets are the tiny blood vessels responsible for forming blood clots; they are often damaged during chemotherapy and cause dangerous bleeding disorders. Dr. Schimmel’s team is developing a TyrRS-based treatment that corrects this damaging side effect.

Dr. Schimmel’s laboratory has also been making strides in cancer prevention. They have found that resveratrol – a natural ingredient found in foods including cacao and grape skins – may have potent preventative effects when combined with tRNA synthetase enzymes and a key protein – PARP-1.

Bio

Paul Schimmel, Ph.D., is a biophysical chemist and he received his B.A. in biochemistry and biophysics from Ohio Wesleyan University in 1962, and then went on to earn his Ph.D. from Massachusetts Institute of Technology (MIT). Currently, Dr. Schimmel is the Ernest and Jean Hahn Professor of Molecular Biology and Chemistry at The Skaggs Institute for Chemical Biology at The Scripps Research Institute. He formerly was the John D. and Catherine T. MacArthur Professor of Biochemistry and Biophysics in the Department of Biology at MIT.

Throughout his career, Dr. Schimmel has received numerous honors and awards, including the American Chemical Society’s Pfizer Award in Enzyme Chemistry, the Biophysical Society’s Emily M. Gray Award for significant contributions to education in biophysics, the Chinese Biopharmaceutical Association Brilliant Achievement Award and the Stein and Moore Award of the Protein Society. He was also elected to the American Academy of Arts and Sciences, the National Academy of Sciences, the American Philosophical Society and the Institute of Medicine. He has also been active in many scientific and academic organizations and committees, including serving as Chairman of the Division of Biological Chemistry of the American Chemical Society. In addition to these honors and positions, Ohio Wesleyan University (his undergraduate alma mater) conferred on him an honorary Doctor of Science Degree.

Dr. Schimmel has given many honorary lectures, including the Peter Debye Lectures (Cornell University), the Sherman Beychok Lecture (Columbia University), the Reilly Lectures (University of Notre Dame), the Mildred Cohn Lecture (University of Pennsylvania School of Medicine), the University Lecture Series (University of Texas Health Sciences Center (Dallas), the Stanley Gill Memorial Lecture (University of Colorado), the Sir Hans Krebs Lecture (Sheffield, UK), the Nucleic Acids Award Lecture (Biochemical Society and Royal Society of Chemistry, UK), Henry Kamin Lecture (Duke University), the Perlman Lecture Award (American Chemical Society) and the Marker Lecture Series (Pennsylvania State University).

Dr. Schimmel is the author or co-author of more than 400 scientific papers and a widely-used three-volume textbook on biophysical chemistry, and he’s an editorial board member of ten different scientific journals. He holds several patents and is a co-founder or founding director of eleven biotechnology companies: Alkermes, Inc., Alnylam Pharmaceuticals, Inc., aTyr Pharma, Inc., Avicena Group, Cubist Pharmaceuticals, Inc., Momenta Pharmaceuticals, Inc., Repligen Corporation, and Sirtris Pharmaceuticals. These companies develop new therapies for human diseases and disorders.

Areas of Focus

Cancer Types

Years of NFCR Funding

1994 – Present

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Alice T. Shaw, M.D., Ph.D.

Massachusetts General Hospital

Boston, Massachusetts
Director of Thoracic Oncology and Attending Physician, Massachusetts General Hospital
Associate Professor Medicine, Harvard Medical School

Research

Dr. Alice Shaw’s laboratory focuses on developing new strategies to overcome lung cancer treatment resistance – specifically for anaplastic lymphoma kinase (ALK), ROS1 and RET genetic mutations in non-small cell lung cancer (NSCLC).

By utilizing a large panel of laboratory research models that were uniquely created at Massachusetts General Hospital, Dr. Shaw and her team developed a new platform to rapidly identify drug combinations for lung cancer patients whose tumors have stopped responding to targeted therapy. Using this platform, they identified several effective drug combinations, including some options that standard testing would not have predicted to work. Moreover, Dr. Shaw and her team assessed tumor biopsy samples to identify biomarkers that could predict how the patients will respond to the combination therapies. These biomarkers may greatly help doctors determine which patient will respond to the newly-discovered drug combinations. With further refinements, this strategy might be used to select the optimal treatment for each individual patient.

Since 2014, Dr. Shaw has been leading several clinical trials and translational efforts aimed at overcoming drug resistance for patients living with ALK+ NSCLC today. Previously, she was the lead investigator for the global registration studies of crizotinib (Xalkori®) and ceritinib (Zykadia®), which led to regulatory approval of both drugs in advanced ALK-rearranged NSCLC. She was also the lead investigator for crizotinib in ROS1-rearranged NSCLC.

She is now focusing new research on the most common site of metastasis for ALK+NCLC – the brain – and looking into why these tumor growths become resistant to crizotinib. Her team launched a clinical trial with the newest ALK inhibitor – lorlatinib – and they are using both tissue and liquid biopsies to identify genetic alterations that may be driving the resistance.

Lastly, since the majority of ALK+ NSCLC patients have no smoking history and do not respond to recently-approved immunotherapies like nivolumab (Opdivo®) or pembrolizumab (Keytruda®), Dr. Shaw is researching the immune microenvironment and other mutations in tumors which may underlie the low response to the new therapies.

Bio

Alice T. Shaw, M.D., Ph.D., received her B.A. in biochemistry at Harvard University and her M.D. and Ph.D. degrees from Harvard Medical School (where she is currently an Associate Professor). She then completed her residency at Massachusetts General Hospital and her postdoctoral work at Massachusetts Institute of Technology. Dr. Shaw was also a fellow at Massachusetts General Hospital and is currently the Director of Thoracic Oncology and an Attending Physician there.

In addition to her funding from NFCR, Dr. Shaw has been awarded other research grants throughout her career, including from the Damon Runyon Cancer Research Foundation, the Burroughs Welcome Fund, the V Foundation for Cancer Research, Uniting Against Lung Cancer and the National Institutes of Health.

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Helmut Sies, M.D.

Heinrich-Heine-Universität

Düsseldorf, Germany
Professor Emeritus, Department of Biochemistry and Molecular Biology I, Faculty of Medicine
Adjunct Professor, University of Southern California at Los Angeles, CA
Professor of Biology and Biochemistry, College of Sciences, Riyadh, Saudi Arabia

Research

Dr. Helmut Sies spent his career studying the role of micronutrients in cancer prevention and specifically focused on carotenoids and flavonoids.

He discovered that lycopene – a carotenoid and antioxidant found in tomatoes and carrots – can reduce the damaging effects of oxygen produced by our body’s essential metabolic processes and has strong skin cancer prevention effects. His research also illustrated how flavonoids (found in cocoa products) can prevent skin damage caused by ultraviolet radiation, improve blood vessel function and reduce cardiovascular risk.

Dr. Sies’ recent research was focused on selenium, a trace metal found in foods such as certain nuts, seafood and organ meats that is essential for good health. Selenium is required to repair oxidative damage in key antioxidant enzymes called seleno proteins. Dr. Sies discovered that not only are seleno proteins strongly decreased in colon cancer tumor cells, but they are also strongly expressed by immune cells in the stomach and gastro-intestinal tract. Moreover, he found that dietary selenium compounds stimulate colon cells to produce seleno proteins. That means that ingested food could provide a potential mechanism for how selenium supports immune health and cancer prevention.

In 1985, Dr. Sies established the concept of oxidative stress. He found that an imbalance between oxidants and antioxidants in favor of the oxidant leads to a redox signaling and control disruption and can cause molecular damage. Click here for Dr. Sies’ latest Annual Review article on oxidative stress.

Additionally, during his career, Dr. Sies studied essential fatty acids that can prevent inflammation and cellular signaling pathways in cancer development, and looked at the role of nitric oxide in cancer and heart disease-related events.

Bio

Helmut Sies , M.D., grew up in northern Germany, where the natural environment instilled in him a fascination with science and discovery. At the age of 17, he traveled to a small town near Cincinnati, Ohio as part of a student exchange program and he lived with a physician whose dedication to medicine had a profound impact upon him. Upon returning to Germany, he graduated from Jakobson-Schule in Seesen in 1961. In 1967, he completed his M.D. certification in Munich.

Dr. Sies served as Professor and Chairman at the Institute of Biochemistry and Molecular Biology at Heinrich-Heine-University Dusseldorf, Germany. He was President of the NRW Academy of Sciences and Arts, Chairman of the Gordon Research Conference on Carotenoids, President of the Society for Free Radical Research International, Vice-President of the Council for the Lindau Nobel Laureates Meetings and a member of the German National Academy of Sciences.

Throughout his career, he received numerous honors and awards, including an Honorary Ph.D. degree from the University of Buenos Aires and an Honorary M.D. from the Universidad de la República, Montevideo. He was awarded the FEBS Anniversary Prize (1978), the Ernst-Jung-Prize for Medicine (1988), the Claudius-Galenus-Prize (1990), the Werner-Heisenberg-Medal of the Alexander von Humboldt Foundation (1999), the Linus Pauling Institute Prize for Health Research (2013) and the Trevor Slater Award of the Society for Free Radical Research International (2014).

Dr. Sies published more than 600 original research papers and book chapters about nutrition, antioxidants, cancer prevention and human health. NFCR funded Dr. Sies’ research for more than 30 years, until his retirement in 2016.

Areas of Focus

Cancer Types

Years of NFCR Funding

1983 – 2016

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