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JOHNS HOPKINS CONQUEST AN UPDATE FROM THE SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER ON ITS MARYLAND CIGARETTE RESTITUTION FUNDS 2013 Turning Research into Results and Results into Revenue A NOTE FROM THE CRF DIRECTORS The success of Johns Hopkins in pioneering medical discoveries and treatment breakthroughs is well documented and understood. The State of Maryland has been our partners in this progress throughout the last decade through the Cigarette Restitution Fund (CRF). We appreciate how steadfast our elected officials have been in protecting these funds and, despite difficult economic times, restoring them to historic levels. They recognize the vital role our institution plays, not only in advancement of medicine, but also in the economic health and growth of Maryland. Our contributions go far beyond the important work at the bench and the bedside. The Johns Hopkins University is the leading private employer in the state. As you will read in this report, relatively small grants made possible through the CRF provide salary support and allow us to bring bright new talent to the Kimmel Cancer Center. With this support, we help these young scientists establish their careers and compete for larger, national grants. These funded investigators hire technicians, administrative and clerical staff. They purchase equipment and service from Maryland vendors, invent new products, and start new companies. Moreover, the jobs created are ones that spark opportunity, are secure, and provide health insurance, education, and retirement benefits. The return on investment, in the form of salaries from job creation and tax revenue, far exceeds the state’s original investment. Whether people come to Maryland to take advantage of unique job opportunities or to receive cancer care that may not be available anywhere else, they contribute significantly to Maryland’s economy. Patients and families do not just buy healthcare in our state, they stay in our hotels, eat in our restaurants, and shop at our stores. Perhaps the best way to fully appreciate Johns Hopkins’ contribution to Maryland and its citizens is to imagine our state without it; consider the human and financial impacts this would have. For certain, we appreciate the funding we have received through the Cigarette Restitution Fund and are grateful to our elected officials who have so diligently worked to maintain this program. The partnership between Johns Hopkins and the state of Maryland is a win-win. CRF support is not only good for Johns Hopkins. It is good for Maryland. Sincerely, William G. Nelson, M.D., Ph.D. Marion I. Knott Professor and Director Johns Hopkins Kimmel Cancer Center John D. Groopman, Ph.D. Professor of Environmental Health Sciences Bloomberg School of Public Health Ø For every CRF research dollar spent, $10 more came back to Maryland in business contracts and other economic development. Ø To date, CRF-supported research has led to patenting and/or licensing of 13 scientific tools or clinical applications. Ø CRF investigators launched two startup companies—Personal Genome Diagnostics and Cureveda—drawing business and revenue to Maryland from around the country and the world. CRF SUPPORT MEANS JOBS FOR MARYLAND In a recent survey by the Association of University Technology Managers, Johns Hopkins surpassed all but two U.S. universities, university systems, and research hospitals in the number of patent applications. In the last five years, Johns Hopkins has seen a 50 percent growth in its patents, launched 61 startup companies, and has more than doubled license revenue from $7 million to $16 million. FROM RESEARCH TO REVENUE: Two CRF Investigators Form Company The Path From Concept to Commercialization èDr. Victor Velculescu relocated to Maryland from California 20 years ago to pursue unique cancer research opportunities at the Johns Hopkins Kimmel Cancer Center. èIn 2004 and 2008 respectively, Dr. Velculescu and Dr. Luis Diaz launched their careers with seed funding from the CRF. èDrs. Velculescu and Diaz became members of the research team that led the world in deciphering the genetic blueprints for cancers. These discoveries led to tests that detect cancer DNA in circulating blood and other bodily fluids and are being used to detect cancer, identify optimal treatments, and monitor tumors’ response to treatment. Drs. Velculescu, Diaz, and colleagues believe these tests may one day be used to prevent cancer by detecting very early molecular changes that precede cancer. èAs a result of this success, their laboratories are expanding. Dr. Velculescu currently has ten employees working directly in his laboratory. The success of the cancer gene discoveries earned him an additional CRF grant to expand his work to lung cancer. As a result he hired three additional employees. In addition, he purchased additional laboratory equipment, which is sold, supported, and serviced by Maryland vendors. èThrough CRF support, Dr. Diaz was recruited to Johns Hopkins and relocated to Maryland from Michigan to work in the laboratory of Dr. Bert Vogelstein, considered by many to be the world’s leading expert on cancer genetics. He now has his own laboratory (for which he leveraged funding through Swim Across America Baltimore) with over 25 employees. Many have relocated from other states to Maryland for an opportunity to work in his laboratory. A dozen more employees work behind the scenes in administrative, budget, public relations, and facilities capacities. èDrs. Velculescu and Diaz do business with hundreds of companies to purchase equipment and supplies. These companies set up offices in Maryland because of business opportunities with Johns Hopkins. èDrs. Veclulescu, Diaz, and collaborators are international leaders in cancer genetics and were the first to perform genome-wide sequence analyses of human cancer. In 2010, the high demand for their expertise and CRF-supported cancer tests resulted in the formation of Personal Genome Diagnostics (PGDx). The company has developed proprietary methods to perform patient-specific analyses of the cancer genome using digital characterization and monitoring technologies. PGDx handles tumor-sequencing requests from scientists all over the globe and has made state-of-the-art genetic analyses available to cancer patients everywhere. Their company, currently located in the Science + Technology Park at Johns Hopkins brings revenue to Maryland from the U.S. and other countries. Pictured above: Genomic technologist Manish Shukla (standing left), lab manager Lisa Kann (seated), and genomic scientist Mark Sausen, prepare samples for DNA sequencing to look for cancer cells at Personal Genome Diagnostics Inc. (Kenneth K. Lam, Baltimore Sun / January 31, 2013) èPersonal Genome Diagnostics started with one employee, grew to four, and currently employs 12 people. The company has been so successful it has outgrown its current facilities and is relocating to new space in Canton. Among the employees working for the company are people who have moved to Maryland from Delaware, Virginia, and Massachusetts. These new citizens are now paying taxes in Maryland, buying real estate and making other purchases that benefit our state economy. èIt all began with investigator funding provided through the CRF. FROM RESEARCH TO REVENUE: CRF Investigators Invent PapGene Cancer Test With cancer gene discoveries that have opened the door to personalized cancer medicine, CRF investigators Victor Velculescu, M.D., Ph.D., Luis Diaz, M.D., (pictured center) and team are considered the world leaders in finding cancer genes and interpreting their usefulness. Their discoveries have led to tests that can find cancer DNA in a small sample of blood or bodily fluids and have been used to detect cancer, personalize therapies to combat the unique genetic alterations contained within a tumor, and to monitor cancers response to treatment. Their goal is to develop tests that will prevent cancer by detecting the earliest genetic changes that precede cancer development. Dr. Diaz’s most recent work uses Pap tests, routinely performed since the 1950s in gynecologists’ offices throughout the country to detect and prevent cervical cancer, to find early endometrial and ovarian cancers. The test, called PapGene, captures DNA that is shed from cancer cells—alterations that Dr. Diaz and team have determined lead to endometrial and ovarian cancer development. The PapGene test extracts the endometrial and ovarian cancer-specific DNA from the same cervical fluid collected during a Pap test to warn of developing cancers. There are currently no early screening tests for endometrial and ovarian cancers, and Dr. Diaz and team’s new test could one day make it possible to test for three female cancers at a woman’s annual wellness exam. This discovery is an example of the innovation that CRF investigator support produces. “This type of funding sparks ideas that save lives,” says Dr. Diaz. In early small-scale studies of PapGene, the test detected 100 percent of endometrial cancers and 40 percent of ovarian cancers. The difference in test sensitivity is a matter of each organ’s proximity to the cervix. The endometrium is in the uterus and sheds a greater number of cells into the cervical fluid collected during a Pap test. On the other hand, cells from the ovaries must travel through the fallopian tubes to reach the uterus and cervix and, therefore, are diminished in numbers and quality. Though Dr. Diaz and team are working to improve PapGene’s sensitivity to ovarian cancer, he says, even at 41 percent, it could help many women. Currently, there is no test for early detection of ovarian cancer, a lethal disease often referred to as the silent killer because it does not cause symptoms and frequently goes undiagnosed until it is well advanced. Dr. Diaz and team have patented PapGene. If the team finds similar results in larger studies, the $100 test could begin to be introduced in doctors’ offices in three to five years. It represents another example of how scientific cancer discovery seeded through CRF funding is making a better Maryland—improving the health of its citizens and its economy. HONOR ROLL OF CRF INVESTIGATORS In 2001, the CRF provided its first research grants to Johns Hopkins. We’re grateful that this vital support continues today. Many of these grants provided seed funding for young investigators. The physician-scientists whose careers were launched with CRF support have since made award-winning research advances, including the first comprehensive gene analysis of cancers, the invention of cancer vaccines and cancer tests, the identification of HPV+ as a distinct and unique subset of oral cancer, the connection of statins to prostate cancer prevention, the identification of a cancerdetoxifying gene pathway and a natural compound that turns it on, and the definition of the field of epigenetics. Other CRF grants have sparked collaborations and made possible transformative laboratory and clinical advances that have helped earn the Kimmel Cancer Center distinction as a “cancer research powerhouse,” “dream team,” and the home of “the most frequently cited research in all of cancer medicine.” Through CRF funding that launched their research, grant recipients have earned millions more in federal grants, patented and licensed inventions, and started new companies. They are considered among the best in cancer research and medicine, and they have been good stewards of CRF awards returning far more to Maryland and its citizens in salaries, revenue, business growth, and additional grants than they received. Meet a Few of Our Many Successful CRF Investigators: Mary Armanios, M.D., linked shortened telomeres to the cancer-related fatal disease idiopathic pulmonary fibrosis. Dr. Armanios collaborates with Carol Greider, Ph.D., whose Nobel-Prize winning research was on telomerase, an enzyme that restores and protects telomeres from damage. The relationship of telomeres and telomerase to cancer development is a major area of research. Dr. Armanios has uncovered mounting evidence that shortened telomeres are related to a number of diseases and cancers, which she characterizes as telomere syndromes. She is working to further decipher the precise role of telomeres in disease and the genetics and biology of telomere-mediated diseases, such as cancer. Stephen Baylin, M.D. (left), James Herman, M.D. (center), Malcolm Brock, M.D. (right), and Charles Rudin, MD. Ph.D., have made breakthrough discoveries in the field of epigenetics, critical cancer-causing alterations to DNA that occur without mutating genes. They led clinical trials of the first epigenetictargeted drug and have leveraged these findings with funding from Stand Up to Cancer to develop an epigenetic-targeted drug combination. The experimental treatment has had unprecedented success against a subtype of lung cancer and shows promise in other cancers, including colon and breast cancers. Shyam Biswal, Ph.D., identified genes that detoxify carcinogens and that also can cause resistance to cancer therapy. He patented agents that target these genes to prevent treatment resistance. His research spurred the company Cureveda as well as plans for another startup company. Michael Carducci, M.D., has overseen a drug discovery pipeline at the Kimmel Cancer Center that has played a key role in advancing the treatment of prostate cancer. He has developed multiple clinical trials to integrate the drugs into standard care. Dr. Carducci, who is co-director of the chemical therapeutics program and prostate cancer and genitourinary program, also is studying pomegranate extract and other natural compounds for their ability to prevent prostate cancer. Luis Diaz, M.D., and Victor Velculescu, M.D., Ph.D., are members of the worldrenowned Kimmel Cancer Center team who completed the first genetic blueprints of cancer and developed tests to detect the cancer-causing alterations. CRF investigator Ben Ho Park, M.D., Ph.D., collaborated with Dr. Velculescu and team to decipher the genetic blueprint for breast cancer. Dr. Diaz collaborated with CRF investigator Richard Roden, Ph.D., when developing the PapGene test for endometrial and ovarian cancers. The discoveries of Drs. Diaz and Velculescu have resulted in a number of patents and the startup company Personal Genome Diagnostics. Charles Drake, M.D., is studying a first-of-its-kind prostate cancer combined therapy that will make surgery an option for more men. Clinical studies, led by Dr. Drake, a cancer immunology expert and co-director of the Prostate Cancer Multidisciplinary Clinic, will include a prostate cancer vaccine. Christine Hann, M.D., Ph.D., is developing novel therapeutics for lung cancer, particularly small cell lung cancer, the most lethal type of the disease. She is studying small molecules that block the BCL2 gene and, as a result, appear to increase the effectiveness of chemotherapy for small cell lung cancer. Dr. Hann’s work has been recognized with the American Society of Oncology Young Investigator Award and Flight Attendant Medical Research Institute Young Clinician-Scientist Award. Anirban Maitra, M.D., is among a select group of researchers who have shown that pancreas cancer, like many types of cancer, contains colonies of cancer promoting cells. These cells, while small in number, appear to be a major force in cell growth by evading anticancer drugs and perpetually giving rise to the larger number of cancer cells that make up the bulk of tumors. Dr. Maitra is studying if targeting these cells with new therapies could help combat pancreas cancer. Elizabeth Platz, Sc.D., co-director of the Kimmel Cancer Center Cancer Prevention and Control Program, used population research to uncover a connection between cholesterol-lowering drugs known as statins and a decreased chance of developing aggressive prostate cancer. A later collaboration with CRF investigators William Nelson, M.D., Ph.D., director of the Kimmel Cancer Center, and Vasan Yegnasubramanian, M.D., Ph.D., co-director of the next generation sequencing laboratory, used a novel combined laboratory research/population science approach to reveal evidence that the commonly-used heart drug digoxin halted prostate cancer cell growth. The team is currently working to better understand the cellular mechanisms with the goal of identifying drugs that can safely treat or even prevent prostate cancer. Kala Visvanathan, M.B.B.S., harnessed the power of sprouts from broccoli seeds for cancer prevention. She is heading clinical trials of broccoli sprouts tea and other preparations to study the natural agent’s ability to detoxify carcinogens. Broccoli sprouts are high in sulphoraphane, which was found by Johns Hopkins researchers to have cancer-preventing properties. FY13 CRF AWARDS Faculty Recruitment: Christine H. Chung, M.D., was selected in a national search to lead the Kimmel Cancer Center’s research in head and neck cancer. She is developing personalized treatments for head and neck cancer based on the unique molecular signatures of tumors. She also is focused on targeted therapies using EGFR inhibitors for non-small cell lung cancer, the most common form of lung cancer. Corrine Joshu, Ph.D., is using population studies to help determine relationships between obesity and gender and colorectal cancer tumor characteristics. Dr. Joshu earned distinction as the Martin D. Abeloff Cancer Prevention and Control Scholar-in Training and is developing straightforward lifestyle strategies that could decrease cancer risk and recurrence. Her studies have linked weight gain and smoking to an increased risk of prostate cancer recurrence. Faculty Retention: Victor Velculescu, M.D., Ph.D., is a member of the world-renowned research team who has deciphered the genetic alterations that drive colorectal, breast, pancreas, ovarian and other cancers and has developed tests that find evidence of these alterations in blood and body fluids. He has received additional CRF support to analyze gene alterations in lung cancer and identify those that can be detected in the blood. Research Grants: Robert H. Brown, M.D., M.P.H.: The Health Burden of Environmental Pollutants in Adipose Tissue Adrian Dobs, M.D.: Community Sample of Medicare Recipients Corrine Joshu, Ph.D.: Colon/Rectum Cancer Tumor Characteristics, Obesity and Gender Norma Kanarek, Ph.D.: Segmentation of Time From First Contact at The Johns Hopkins Hospital for Early Stage Non Small Lung Cancer Michael Trush, Ph.D.: Cancer Education and Services Outreach Effectiveness at Baltimore City’s Northeast Market Scott Zeger, Ph.D.: Data Science Infrastructure for the Johns Hopkins Optimizing Cancer Screening Working Group and Prostate Cancer Decision Support Richard Zellars, M.D.: Patient Support Interventional Study KIMMEL IN THE COMMUNITY Helping Maryland by Strengthening Its Communities Though the CRF Public Health Grant at Johns Hopkins was discontinued in 2011, we remain committed to educating Marylanders about cancer prevention and screening and caring for our state’s underserved and uninsured. The Kimmel Cancer Center has partnered with the Baltimore City Health Department to ensure cancer education and screening is available to underserved Baltimore citizens. Johns Hopkins voluntarily joined programs like Priority Partners, a managed care organization that provides healthcare to the uninsured, long before the discussion of federally mandated national healthcare began. This is not basic healthcare. This is care that is equal to, and in many cases exceeds, that offered through premier commercial insurance plans. Stocking Up on Healthcare Information at the Market: Kimmel Cancer Center experts are taking cancer education to the community. A small CRF research grant has allowed Johns Hopkins to expand and evaluate its Market Day program, which takes wellness services, such as blood pressure screening, and cancer education, on the road to visitors of the Northeast Market. The CRF grant funds cancer prevention and screening information provided by experts. Smoking Cessation: Experts estimate that more than 80 percent of cancers are caused by smoking. Getting people to quit smoking is necessary to control Maryland’s cancer rates. Several smoking cessation endeavors in conjunction with the Kimmel Cancer Center’s “Ask the Experts” and Community Relations Programs, the Department of Health Behavior and Society, and the Global Tobacco Institute are providing information and resources to encourage and help patients and members of the community quit smoking. Minority Participation in Clinical Trials: Overcoming cultural and institutional barriers and increasing minority participation in clinical trials is a priority of the Kimmel Cancer Center. Center leadership has expanded these initiatives appointing an Assistant Director for Clinical Trial Accrual to develop and oversee initiatives to increase minority accrual to therapeutic clinical trials and a research nurse to improve clinical trials communication, continuity of care, and data management. B’More Healthy Expo: Nurses from each of the Kimmel Cancer Center’s clinics are volunteering at the B’More Healthy Expo on February 23rd to provide expert advice and information to the public on healthy behaviors, such as nutrition, physical activity, smoking cessation, and cancer screening. Useful giveaways, such as cutting boards and nutrition handouts, as well as interactive games will be used to help get the word out about healthy behaviors that help prevent cancer. Kimmel Cancer Center Day of Service: In honor of the Kimmel Cancer Centers 40th anniversary, faculty and staff will be volunteering at local non-profits. In addition, members of the community (neighbors, students, teachers, and others) will be invited this Spring to an open house at the Science + Technology Park at Johns Hopkins to learn about the companies and businesses coming to the community, interact with scientists, and learn about the many job opportunities at the biotech park. Caring for the Underserved: The Kimmel Cancer Center continues to provide cancer screening to Maryland’s underserved populations through Priority Partners, a Medicaid managed care organization, and Johns Hopkins Community Physicians. Physicians from our gastrointestinal cancer program partner with the Baltimore City Health Department to provide colonoscopies to uninsured Baltimore residents. The Johns Hopkins Center to Reduce Cancer Disparities: Building upon the framework established through the Cigarette Restitution Fund public health grant, Kimmel Cancer Center has a dedicated team of experts addressing cancer disparities through community-based participatory education, training, and research among racial/ethnic and underserved populations. As part of this initiative, our East Baltimore Medical Center is hosting an information session and discussion, “From Survive to Thrive: Equipping Cancer Patients to Live Their Best Life,” on March 12, 2013, with Congressman Elijah Cummings. Topics include resources and support available to cancer patients and survivors, practical tips on living healthy, free prevention services, and resources available at local treatment locations. Representatives from the Johns Hopkins School of Medicine, Baltimore City Cancer Program, and prostate and breast cancer survivors and advocates also are participating in the event. Speakers Bureau: Upon request, the Kimmel Cancer Center provides free expert speakers to attend meetings of community gatherings and organizations, businesses, churches, and other groups to discuss topics related to cancer.