JOHNS HOKINS MEDICINE

Johns Hopkins Medicine is a more than $4 billion enterprise uniting physicians and scientists of The Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of The Johns Hopkins Health System.

Johns Hopkins Medicine has provided international leadership in the education of physicians and medical scientists in biomedical research and in the application of medical knowledge to sustain health since the opening of The Johns Hopkins Hospital in 1889. The Johns Hopkins Health System includes three acute care hospitals – The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center and Howard County General Hospital – which together provide an integrated health care delivery system: long-term care, home care and outpatient care.

The mission of Johns Hopkins Medicine is to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, Johns Hopkins Medicine educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness.

JOHS HOPKINS UNIVERSITY SCHOOL OF MEDICINE

The Johns Hopkins University School of Medicine is ranked the number two medical school in the nation by U.S. News & World Report. For the 13th straight year, The Johns Hopkins University School of Medicine ranks as the top recipient of National Institutes of Health (NIH) research dollars.

The Johns Hopkins University School of Medicine educates medical students, graduate students, and postdoctoral fellows in accordance with the highest professional standards; to prepare clinicians to practice patient-centered medicine of the highest standard; and to identify and answer fundamental questions in the mechanisms, prevention and treatment of disease, in health care delivery and in the basic sciences.

The School of Medicine has a distinguished faculty, which has included three Nobel Laureates, 11 Lasker awardees, 12 members of the National Academy of Sciences and 32 members of the Institute of Medicine of the National Academy of Sciences. Currently there are 2,371 full-time and 1,199 part-time faculty, nearly 700 Ph.D. candidates, more than 1,400 fellows and about 500 medical students, roughly 50 of whom are pursuing a joint M.D./Ph.D. degree. While research is not required of medical students, nearly 80 percent are involved in research.

The fifteen graduate programs are: Biochemistry, Cellular & Molecular Biology, Biological Chemistry, Biomedical Engineering, Cellular & Molecular Medicine, Cellular & Molecular Physiology, Functional Anatomy & Evolution, Health Sciences Informatics, History of Science, Medicine & Technology, Human Genetics & Molecular Biology, Immunology, Medical & Biological Illustration, Neuroscience, Pathobiology,

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Pharmacology & Molecular Sciences, and the Program in Molecular and Computational Biophysics.

THE JOHNS HOPKINS HEALTH SYSTEM CORPORATION AND AFFILIATES

The Johns Hopkins Health System Corporation (“JHHSC”) is a private, non-profit, non-stock, membership corporation organized under the laws of the State of Maryland to formulate policy among and provide centralized management for JHHSC affiliates. JHHSC provides certain shared services including purchasing, legal, advertising, finance, and other functions. JHHSC functions as the parent holding company of its affiliates. JHHSC is the primary affiliate of The Johns Hopkins University (“JHU”), which includes The Johns Hopkins Schools of Medicine (“SOM”). The Johns Hopkins Health System Corporation and its Affiliates are dedicated to providing the highest quality patient health care in the treatment and prevention of human illness through the principal system affiliates described below. JHHS offers a full continuum of integrated healthservices in settings ranging from primary care physician offices and ambulatory care centers, acute care services provided at three hospitals, to sophisticated quaternary patient care. All levels of care are offered on an inpatient and outpatient basis, as well as rehabilitation, chronic care, skilled nursing home care and home health care services. The medical staffs of the JHHS are predominantly members of the JHU SOM faculty.JHHS is an academically based health system that serves the greater Maryland area and many national and international patients. When you count both JHHS and JHU, Johns Hopkins boasts a total employee count of over 40,000, making them the single largest private employer in State of Maryland. In addition to the research conducted on its East Baltimore campus, the SOM conducts research into respiratory disease, gerentological illness, and drug abuse on Bayview campus described below. The National Institute of Health (“NIH”) leases facilities on the Bayview campus for the National Institute on Drug Abuse and the National Institute on Aging. The NIH has Congressional approval to construct a new facility on the Bayview campus. Neither JHHS nor JHU will be liable for the debt issued to finance construction of the facility.

THE JOHNS HOPKINS HOSPITAL (JHH)

JHH is organized as a not-for-profit Maryland corporation that operates a 1,017-licensedbed (956 acute beds, 45 Neonatal Intensive Care bassinets and 14 ComprehensiveInpatient Rehabilitation beds) facility on the east side of the City of Baltimore. JHH is aworld-renowned academic medical center providing tertiary and quaternary care, whichdraws patients not only from metropolitan Baltimore and surrounding counties, but alsofrom a five-state radius as well as the rest of the United States and over 100 countries.JHH has been recognized as one of America’s best hospitals, and is home to manycenters including the Brady Urological Institute, the Sidney Kimmel ComprehensiveCancer Center, the Wilmer Eye Institute, the Clayton Heart Center, and the JohnsHopkins Children’s Center. The Robert Heyssel Outpatient Center provides high qualityambulatory care services using state-of-the-art diagnostic facilities, imaging equipment,and operating rooms. JHH is the MIEMMS designated pediatric and eye trauma center(maternal transport, adult trauma) neonatal intensive care unit that are part of the

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Maryland statewide emergency medical system. ACS trauma certification.

JOHNS HOPKINS BAYVIEW MEDICAL CENTER, Inc. (JHBMC)

JHBMC is a not-for-profit Maryland corporation that operates a community basedteaching hospital and long-term care facility. JHBMC offers a broad range of inpatientand outpatient services and includes a trauma center and neonatal intensive care unit thatare part of the Maryland statewide emergency medical system. Services offered atJHBMC also include JHBMC’s Burn Center, the only regionally designated center forburn treatment in Maryland. JHBMC’s acute hospital has 316 licensed acute beds and 25Neonatal Intensive Care bassinets. JHBMC is also the site of the Johns Hopkins Bayview Care Center which provides long-term care, subacute care, chronic medical, ventilator, rehabilitation services, and outpatient care to geriatric patients and post-acute patients. Long-term care facilities include 200 licensed skilled nursing beds, 69 licensed chronic hospital care beds, and 6 licensed comprehensive inpatient rehabilitation beds. JHBMC is also the site for 32 residential assisted living beds for substance abuse treatment, including the Center for Addiction and Pregnancy.

HOWARD COUNTY GENERAL HOSPITAL, INC. (HCGH)

HCGH is a not-for-profit Maryland corporation that has 204 acute beds and 18 NeonatalIntensive Care bassinets operating in this community hospital in Columbia, Maryland.HCGH is the only hospital in an affluent county located between Baltimore andWashington, D.C. HCGH offers a full range of acute care inpatient services includinggeneral medicine, obstetrics, cardiology, orthopedics, general surgery, infectiousdiseases, oncology, gynecology, neurology, pediatrics, and psychiatry. HCGH alsoprovides critical care services and operates a nursery. HCGH also offers extensiveoutpatient services including outpatient surgery in a state-of-the-art facility locatedadjacent to the main building, known as The Center for Ambulatory Surgery (“TCAS”).TCAS features six operating rooms, one minor procedure room, and one cystoscopysuite. HCGH recently expanded its adult and pediatric emergency services, as well as itslabor and delivery, neonatal intensive care, and prenatal units—all to improve access andmeet growing community demand.

Other components of the JHHS include: Johns Hopkins Community Physicians, INC. The Johns Hopkins Medical Services Corporation Howard County Health Services, Inc. Johns Hopkins Medical Management Corporation Ophthalmology Associates, LLC Johns Hopkins Employer Health Programs, Inc. Johns Hopkins HealthCare, LLC

INSTITUTE OF BASIC BIOMEDICAL SCIENCES

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The Johns Hopkins Institute for Basic Biomedical Sciences was created in December 2000 to form a cohesive infrastructure for the School of Medicine's nine basic science departments: Biological Chemistry, Biomedical Engineering, Biophysics and Biophysical Chemistry, Molecular Biology and Genetics, Molecular Cell Biology, Neuroscience, Pharmacology, Molecular Sciences and Physiology, and Comparative Pathobiology.

The Institute for Basic Biomedical Sciences is dedicated to supporting faculty who conduct fundamental research at the Johns Hopkins School of Medicine. Through the identification and development of cross-disciplinary centers that bring together researchers whose methodologies differ, but whose scientific interests overlap, the IBBS also will reinforce the bright future of basic science research at the School of Medicine, provide important research resources for all researchers and facilitate opportunities for collaboration among all faculty.

SIDNEY KIMMEL COMPREHENSIVE CANCER CENTER AT JOHNS HOPKINS

Since its inception, the Sidney Kimmel Comprehensive Cancer Center has been dedicated to better understanding human cancers and finding more effective treatments. The Cancer Center was one of the first in the country to be designated by the National Cancer Institute (NCI) as a Comprehensive Cancer Center and is the only one in the state of Maryland. The Kimmel Cancer Center has active programs in clinical research, laboratory research, education, community outreach, and prevention and control.

Patients who visit the Kimmel Cancer Center have access to some of the most innovative and advanced therapies in the world. Because Center clinicians and research scientists work closely together, new drugs and treatments developed in the laboratory are quickly transferred to the clinical setting, offering patients improved therapeutic options.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins encompasses a wide spectrum of specialty programs for both adults and children coping with cancer, including bone marrow transplantation and new drug development. Additionally, those at high-risk for breast, ovarian, colon and other cancers, may seek information about early detection, prevention and genetic counseling through a comprehensive genetics service.

The Center also offers complete family and patient services that include a Cancer Counseling Center, survivors and palliative care programs, and two residences for patients traveling from out-of-town to receive treatment.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins continues to build on its strong foundation of innovative fundamental cancer research; and has utilized its considerable institutional commitment, extramural and philanthropic support, vigorous faculty recruitment and facility development to greatly enhance the interactions between basic scientists, clinical investigators, and population-based investigators in building a

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robust array of innovative translational research studies. Within the last 10 year, three state-of-the-art facilities were built for cancer research and patient care.

Facilities. The Harry and Jeanette Weinberg Building is the center’s clinical facility and opened in 2000. It has:

350,000 net square feet 9 floors 3 floors underground, a portion of which is designated for patient and visitor

parking Glass-enclosed walkway connects to main hospital building Ambulatory Services Inpatient and Outpatient Surgical Center 16 Operating Suites Post anesthesia care unit 62 Medical Oncology Beds (includes Hematologic Oncology and Bone Marrow

Transplant) 72 surgical beds 20 intensive and intermediate care beds Anesthesiology Inpatient/outpatient Continuum of Care (IPOP and HIPOP) Gynecologic Oncology, Gynecology, Uro-gynecology, and Reproductive

Endocrinology Image Recovery Salon Pathology Patient and Family Services Pharmacy Physical Therapy Radiology Radiation Oncology Chapel, Auditorium and Conference Rooms

Research Programs. The Bunting-Blaustein Cancer Research Building, in operation since 1999, holds the following research programs:

Cancer Biology, including molecular genetics and molecular virology Breast Cancer Cancer Immunology Prostate Cancer Viral Oncology

GI Cancer Chemical Therapeutics Hematologic Malignancies Pediatric Oncology

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The 10-story building 122,000 net square feet with working space for 400 researchers and staff. In addition to laboratories and offices, the building houses support spaces which include a 6,000-square-foot vivarium, a BL-3 lab, glass wash, irradiators, and laboratory services.

In the March 2006, the David H. Koch Cancer Research Building opened. It is a twin in design and construction to the Bunting-Blaustein Cancer Research Building and houses research programs in:

Brain Cancer Radiation Oncology and Molecular Radiation Sciences Pancreas Cancer Skin, lung, and head and neck cancers. 

A 250-seat, high-tech auditorium connects the two research buildings.

In addition, programs in cancer prevention in control, cancer imaging, and female reproductive cancers are conducted by Cancer Center faculty located in a number of departments and schools at Johns Hopkins, including the School of Medicine, the Bloomberg School of Public health, the School of Nursing and the Whiting School of Engineering.

The Cancer Center has been awarded seven SPORES (Specialized Programs of Research Excellence) by the National Cancer Institute in Lung, GI, Prostate, Breast, Head and Neck, Lymphoma and Cervical cancers.

Shared Resources. The following facilities and resources support cancer research across various Johns Hopkins departments and divisions.

Animal Resources Bioinformatics

Microarray

Cancer Functional Imaging

Cell Imaging

Common Equipment

Cytogenetics

Experimental Irradiators

Flow Cytometry

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Glassware Washing

Mass Spectrometry

Medicinal Chemistry Core

Specimen Accessioning Core

Tissue Microarray Core

Pharmacology Analytical Core

Cellular Therapy Core (GEL)

Cell Processing and Gene Therapy

Human Immunology Core

Research Informatics

Clinical   Protocol Review and Monitoring System  Biostatistics

Research Pharmacy

Clinical Research Office

Clinical Research. The Cancer Center has more than 230 therapeutic trials open to accrual. Information about each study, including eligibility criteria, can be found on the Cancer Center’s Web site: www.hopkinskimmelcancercenter.org. In addition, the Center funds a full-time clinical trials information specialist and designated phone number. This position is staffed by an experience research nurse who answers calls from referring physicians, patients, families, and the public.

Radiation Oncology. In 2003, Johns Hopkins appointed Theodore DeWeese, M.D., as the first Chair of the newly created Department of Radiation Oncology and Molecular Radiation Sciences. This department was established in July 2003 from the former Division of Radiation Oncology in the Department of Oncology. Dr. DeWeese’s clinical interests focus on prostate cancer and the development of novel therapeutics for the disease. His clinical research is a direct translation of work from his laboratory with a particular interest in developing salvage therapies for men with a rising PSA following definitive therapy.

Pediatric Oncology. The Division sees more than 1000 visits each year, treating children from infancy through age 21. Areas of expertise include bone marrow transplantation, leukemia, sarcoma, histiocytosis, Hodgkin’s disease, brain cancers and long-term

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survivorship issues. Outpatients are seen on the eighth floor of the Johns Hopkins Outpatient Center and inpatients are treated in the Johns Hopkins Children’s Center. A new Children’s Hospital is scheduled for completion in 2009. A pediatric oncology fellowship program, organized with the National Cancer Institute, selects seven fellows per year are selected through the National Residency Matching Program (NRMP) to train each year in the program. The fellowship is designed to provide clinical and research exposure that allows for the development of subspecialist academicians adept in laboratory and/or clinical research, coupled with superior patient management skills.

Research Program DescriptionsFor full listing of faculty in each program, visit www.hopkinskimmelcancercenter.org.

Cancer Biology

In Cancer Biology, researchers work to reveal and understand the various steps that cause a normal cell to turn malignant.  From molecular genetic alterations—those that change cells by mutating its DNA—to epigenetic alterations—those that change cells without a mutation, investigators are uncovering and understanding key genes and gene pathways involved in cancer.  Starting with a cell’s earliest origins as a stem cell through its evolution to malignant cell, researchers are deciphering the biological transformations that lead to cancer and those that occur in the tumor cell to cause it grow and spread.  This ever growing understanding of the cellular origins and promoters of cancer has resulted in new tests for early cancer detection and cancer susceptibility, new diagnostic methods using molecular markers of cancer, opportunities to prevent cancer, and new treatments. Cancer Immunology

The immune system is the body’s first line of defense against most diseases and unnatural invaders, so why it most often overlooks the presence of cancer cells has been a complex cellular mystery. For this reason, understanding how the immune system works—or does not work—against cancer is a main focus of Cancer Immunology investigators. By deciphering the cellular mechanisms that turn on and regulate immune responses researchers have been able to develop immune therapies that trigger immune cells to attack cancer cells and, at the same time, boost the effectiveness of other therapies. Vaccines, gene therapy, and blood stem cell therapies are just a few of the novel approaches that, combined with other therapies, have been successful in combating a variety of cancers, including leukemia and breast, pancreas, prostate, kidney, and cervical cancers.

Investigators seek also to understand how the survival, proliferation, and differentiation of normal and malignant stem-progenitor cells are regulated. Their studies are focused on the cell and molecular biology of the earliest embryonic stem cells, the stem and progenitor cells that form the normal blood and immune systems, and the malignant counterparts of these stem-progenitor cells, the leukemias. Projects include using preclinical genetic engineering of hematopoietic stem cells that will resist rejection, and

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studies of hematopoietic growth regulatory genes to elucidate the molecular steps in the development of leukemias and other cancers from normal human stem-progenitor cells.

Viral Oncology

There is perhaps nothing more efficient than a virus at disrupting cellular pathways. While scientists have long been aware of the association between cancer and viruses, such as the Epstein-Barr virus (EBV) and human papilloma virus (HPV), and in more recent years, Cyto-meglavirus (CMV) and Kaposi’s Sarcoma Herpes Virus (KSHV), they are now beginning to decipher the precise role they play in cancer initiation. Hodgkin’s disease, cervical cancer, head and neck cancers, and AIDS-related malignancies are among the cancers known to be virus driven. Understanding the interaction between viruses and cells is the basis for developing diagnostic and therapeutic strategies. In addition, because viruses do their work by infiltrating cell pathways, they provide a unique window into the cellular reprogramming that puts the cancer process in motion.

Cancer Prevention and Control

While cancer is now recognized as a genetic disease, Cancer Prevention and Control investigators also realize that most of the gene mutations that lead to cancer are acquired not inherited.  As a result, this provides many opportunities for prevention through behavioral and environmental modifications to derail cancer initiation. Many of the most common cancers are caused by environmental and behavioral factors that are known and potentially alterable.  Among these things are HPV infection, inflammation, poor diet, and smoking.  Since it is clear that not all individuals with known risk factors develop cancer, investigators also are working to understand the unique biology that connects risky behaviors and environmental exposures to cancer development.  This research is leading to behavioral interventions, chemoprevention strategies, and the identification of biomarkers of risk exposure.

Chemical Therapeutics

Drugs that attack cancer cells have been and continue to be one of the most effective ways to fight cancer. Cellular and molecular genetic discoveries about the cancer cell in recent years have opened the door to a new era of drug therapy, known as Chemical Therapeutics, that allow clinicians and investigators to identify and target the Achilles’ heel of the cancer cell. Today’s anticancer drugs kill tumor cells more effectively with much less toxicity to normal cells. Trademark side effects, such as hair loss and nausea, are becoming less common. Often referred to as biologics, these new therapies are targeted specifically to the cellular characteristics of a person’s cancer, those things that researchers now know go awry to allow the initiation and progression of cancer. Whether it is interfering with a cancer gene pathway, cutting off the blood supply to tumors, or blocking proteins that accelerate cancer cell growth, investigators have identified existing drugs, and developed new ones, to put the brakes on cancer growth.

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Cancer Imaging

One of the more difficult challenges in cancer research is that scientists are delving into cellular and molecular genetic mechanisms that cannot be seen by the human eye with even the strongest of microscopes. The newly emerging field of Cancer Molecular Imaging is advancing the understanding of the disease by allowing investigators a non-invasive live view of the cellular and molecular events involved in the cancer process. Our investigators use such technologies as MRI (magnetic resonance imaging), PET (positron emission tomography), SPECT (single photon emission computed tomography), optical imaging, and ultrasound to image and compare gene pathway expression, protein interactions, small animal models, tumor blood supply, cell metabolism, unique characteristics of metastatic cells, and the affects of new therapies on cancer. This new insight into the cancer process promises to speed up basic research and its clinical translation to the bedside.

Hematological Malignancies and Bone Marrow Transplant

Cancers of the blood and lymph system, such as leukemias and lymphomas, are the main focus of investigators in the Hematologic Malignancies and Bone Marrow Transplant Program. They are studying cancer stem cells, viruses, genetics and other key factors to uncover the biology driving these diseases, causes of treatment resistance, and new targeted therapies. As bone marrow transplantation, or the replacement of diseased bone marrow (the blood cell factory) with healthy marrow from the patient or a donor, is often the treatment of choice, our researchers are developing and refining techniques in bone marrow graft engineering, mismatched marrow donations, and vaccine approaches that minimize side effects and complications, making this therapy more tolerable and more effective for patients.

Prostate Cancer

Prostate cancer continues to be the most frequently occurring cancer in men, and our research team is focused on all aspects of the disease, from the unique biology of this cancer to improved screening and prevention strategies, diagnostic methods, and therapies that target these cellular characteristics. Investigators are studying environmental factors, such as diet, inflammation, and immunity, as well as genetic determinants, such as methylation, hormone function and DNA damage repair mechanisms that put men at risk for prostate cancer. The discovery of new serum biomarkers are expected lead to better methods of early detection and monitoring of disease. New drug therapies that keep both early and late disease in check are another major area of research. So-called pro-drugs and cancer vaccines that selectively target and kill prostate cancer cells are improving treatment results for many men.

Breast Cancer

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While mammography and genetic discoveries have greatly improved early detection, many women continue to suffer recurrences of disease. Investigators have been working to decipher the cellular pathways, hormonal characteristics, and other triggers that cause of the growth and progression of breast cancer cells. Molecular genetic “signatures” that distinguish cancers likely to spread from less aggressive forms are providing the foundation for new drugs tailored specifically to attack these unique cells. A new class of drugs, known as aromatase inhibitors, and a therapeutic vaccine are other promising areas of recurrence prevention and treatment.  

Gastrointestinal Cancer

Gastrointestinal (GI) cancers, including colorectal and pancreatic cancers, have long been a major focus of our investigators who have completed landmark studies and comprehensive models of the molecular genetic causes of these diseases. The multi-specialty approach, resources, and experience of the Bowel Tumor Working Group, established in the 1980s, and the Pancreatic Cancer Working Group, established in 1991, has led to many new findings and incremental treatment gains in some of the most difficult of tumors. Now, this body of knowledge is being further developed and expanded through this new GI cancer-specific research program to identify the unique biological components of GI cancers, identify and assess risk factors, and develop new targeted treatments and novel methods of testing potential drug therapies.

Upper Aerodigestive Cancer

Smoking continues to be a leading cause of cancer. Investigators in the newly developed Upper Aerodigestive Cancer program focus their attention on cancers most directly linked to tobacco use, including lung, head and neck, and esophageal cancers. Among their discoveries is the identification of a series of molecular events that contribute to cancer development. These events include both genetic mutations and other molecular alterations affecting gene expression. Taken together, these molecular markers are being used to detect precancerous changes, to diagnose cancers, and to guide surgeons in removing tumors. In oral cancers, where every cut can potentially impact a patient’s speech or appearance, these markers may help surgeons precisely pinpoint cancer cells and spare normal tissue. These molecular events also represent potential targets for improving drug therapy for these diseases. A number of new biologic therapies directed against molecular alterations specific to the cancer are being evaluated and show promise for patients with cancers of the lung, head and neck and esophagus.

Brain Cancer

Brain cancer, though relatively rare, poses scientists with some of the most difficult problems. The brain is not only the control center for all physiological functions, but is  also the keeper of all that is truly human—emotions, memory, and personality.  It makes cancer treatment, at once, urgent and guarded, as clinicians work to kill the cancer without harming the brain. Working against them is the blood brain barrier, the brain’s

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own protective mechanism against toxins and other invaders, which often keeps anticancer drugs from getting to tumor cells. In addition, these cancers are often not well contained stretching out like fingers across vital brain tissue, making surgical removal difficult. Our investigators are working to combat these challenges with sophisticated new brain imaging techniques as well as a better understanding of the biochemical, molecular, and genetic events involved in these cancers.  The identification of new cancer-associated pathways responsible for tumor growth and the development of drugs that block the activity of these pathways are showing promise in improving treatment outcomes.

Female Reproductive Cancers

The new Female Reproductive Cancer program allows investigators to focus on ovarian, cervical, uterine and other cancers affecting women in significant numbers. Surveillance programs that monitor high risk women and the discovery of biomarkers that support early detection of stealth cancers, such as ovarian cancer, that often go undetected until advanced, are changing outcomes for many women. New therapies, including a cancer vaccine that attacks established cervical cancer and drugs that target ovarian cancer stem cells may decrease common ovarian cancer recurrences. These and other discoveries promise to improve the diagnosis and treatment of these cancers. 

THE JOHNS HOPKINS CHILDREN’S CENTER

Founded in 1912 as the children’s hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children’s Center offers one of the most comprehensive pediatric medical programs in the country, from performing emergency trauma surgery, to finding causes of and treatments for childhood cancers, to delivering a child’s good bill of health. With recognized Centers of Excellence in 20 pediatric medical sub-specialties including cardiology, neurology, psychiatric illnesses and genetic disorders, Children’s Center physicians, nurses and staff provide compassionate care to more than 100,000 children each year.

Consistently ranked as one of the top three children’s hospitals in the nation by U.S. News and World Report, the Children’s Center advances pediatric medicine through the translation of novel research into state-of-the-art patient care and training of young physicians, resulting in a synergistic bench-to-bedside approach to medicine. The Children’s Center includes a federally designated Clinical Research Unit and is awarded annually in excess of $30 million for research in pediatric disorders.

One of only 10 federally designated pediatric clinical research units in the United States, the Children’s Center is Maryland’s most comprehensive, acute-care hospital for children offering state-of-the-art multi-disciplinary care to patients from across the state of Maryland and around the world. The Children Center’s Pediatric Trauma Service and Burn Unit are Maryland’s state-designated trauma and burn centers for children. It is the community hospital and primary outpatient care center for children in East Baltimore.

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More than 8,100 patients were admitted in fiscal year 2006, with approximately 23,000 children being treated in the pediatric emergency department.

The formal groundbreaking for the Johns Hopkins Hospital’s new clinical towers, one of which will be the new Children’s Hospital of Johns Hopkins, took place on June 5, 2006. This project is the core of the medical campus’s $1.2 billion redevelopment plan. Six years in the making, the groundbreaking marked the most ambitious redevelopment in the Hospital’s history and the official start of one of the largest single health care construction projects in the United States.

The new children’s hospital building, scheduled for completion by 2010, will be a state-of-the-art 205-bed facility, with all the best that current technology has to offer and the flexibility to expand to meet tomorrow’s discoveries. It will house emergency, surgical, interventional, critical and acute care for infants and children and will integrate care of high-risk obstetrics patients and newborns. The new facility will have sufficient capacity to maintain its current status as the designated pediatric trauma center for the state of Maryland. In addition, the David M. Rubenstein Child Health Building and Pediatric Burn Center at Johns Hopkins Children’s Center, a new $20 million, four-story, 90,000-square-foot pediatric outpatient facility situated across the street, will provide one-stop outpatient services for pediatric patients.

Johns Hopkins Children’s Center employs approximately 1100 people and has 230 full-time pediatric faculty. There are approximately 30 medical and surgical subspecialties. Many of them are advancing the standard of pediatric care through Centers of Excellence, which include allergy & asthma, genetic disorders, surgery & pain control, cystic fibrosis, transplants, sleep & breathing disorders, kidney, urinary tract disorders, among others. For 100 years, the Johns Hopkins Children’s Center has been world-renowned for rapidly translating laboratory research into exceptional patient care. This is done through multi-disciplinary collaborations of sub-specialists, each bringing their own unique perspective and expertise to questions of science and medicine.

Among numerous medical breakthroughs over the past century, physicians at the Johns Hopkins Children’s Center have been credited with the:

First successful “blue baby” operation to correct congenital heart defects First identification of three types of polio virus needed to make a polio

vaccine First preventive treatment for rheumatic heart disease Ground-breaking treatment for the painful crises of sickle cell anemia Discovery of one of the first methods of gene therapy for cystic fibrosis Discovery of the Ketogenic Diet to treat epilepsy

Training the next generation of pediatricians remains in the 21st century as central to the Johns Hopkins mission as it was in 1912, when the Children’s Center opened its doors as the Harriet Lane Home for Invalid Children. A century ago, Harriet Lane residents were among the first in the country to train in pediatrics within an academic school of

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medicine. Today, they complete a rigorous and comprehensive program in both inpatient and outpatient settings.

The pediatric residency curriculum at Johns Hopkins Children’s Center focuses on teaching young pediatricians not only to care for an inpatient population, but also to manage their care in clinics, at home and at school. Seventy pediatric residents, working closely with faculty and fellows, complete resident rotations that are organized into sub-specialty and general service teams within the hospital and in outpatient settings, enabling experience in the full scope of pediatric practice. This is consistently rated among the top three pediatric training programs in the nation by U.S. News & World Report.

For almost 100 years, the Johns Hopkins Children’s Center has been world-renowned for rapidly translating laboratory research into exceptional patient care. This is done through multi-disciplinary collaborations of sub-specialists, each bringing their own unique perspective and expertise to questions of science and medicine. Researchers at the Johns Hopkins Children’s Center are among the pioneers of molecular genetics. Discoveries that probe, analyze and manipulate genes now point the way to a second century of unprecedented medical progress.

Research underway at the Johns Hopkins Children’s Center promises progress against cystic fibrosis and other pulmonary disorders, childhood cancers, heart disease, emotional and neurological disorders, sickle cell anemia and other blood disorders, and many other diseases that strike children.

Allergy and Immunology

The division has active laboratory-based and clinical research programs and publishes over 50 scientific papers annually. The faculty has diverse research interests and is actively involved in studies that will improve the care of patients with asthma, food allergy, primary immune deficiency, and ataxia telangiectasia. Three faculty members have leadership roles in the Inner-city Asthma Consortium, a network that was formed in 2003 to combat the inner-city asthma epidemic. In addition, two are investigators in the Center for Childhood Asthma in the Urban Environment, an NIEHS and EPA funded Center that studies the role of environmental exposures in inner-city asthma. The division’s director is the principal investigator for studies of the natural history of food allergy and the treatment of peanut allergy that are being conducted as a part of the Food Allergy Consortium, an NIH-sponsored consortium that has been charged with improving the diagnosis and treatment of food allergy. One faculty member is funded by the Ataxia Telangiectasia Medical Research Foundation and conducts clinical and laboratory-based studies with the primary aim of elucidating the pathogenesis of AT and improving the lives of patients with AT.

Endocrinology

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Faculty members in the Division of Pediatric Endocrinology are focused on studies of reproduction and growth. The development and function of the gonadotropin-releasing hormone (GnRH) neuron is of particular interest. GnRH has a central role in the control of puberty and reproduction by directing pituitary secretion of luteinizing hormone and follicle stimulating hormone, which in turn regulate the synthesis of gonadal estrogen and androgen. The laboratory has developed and characterized the first GnRH-secreting cell lines from mice. Using these cell lines and transgenic mice, investigators have identified cell-specific elements responsible for GnRH expression. This division also studies basic mechanisms of estrogen action in the reproductive axis using gene knock-out technology. Researchers are studying insulin signaling in GnRH neurons and its role in the nutritional control of reproduction. This was the first laboratory to show that a mutation in a pituitary transcription factor caused a human disorder. The laboratory now studies over 30 different transcription factors in humans with short stature and/or other deficiencies in anterior pituitary hormones. Investigators are also interested in G-protein signaling defects in patients with pseudohypoparathyroidism and short stature.

Institute of Genetic Medicine

The IGM has 17 members and 6 affiliated members who have primary appointments in the Department of Pediatrics.The research activities of these individuals focus on identification of disease genes, understanding disease mechanisms (pathophysiology) and treatment or prevention of disease. The disease gene identification activities include recognition of genes that either cause or modify single gene disorders or alter risks for complex multigene traits. For example, investigators are working on identifying:

o genes that increase susceptibility for neurodevelopmental disorders such as schizophrenia and bipolar disease

o genes that cause mental retardationo genes that cause abnormalities of vascular development and/or

extracellular matrix function such as the Marfan syndromeo genes that either cause or modify cystic fibrosis–like phenotypes o the pathophysiology of disorders causing hypotonia such as the

muscular dystrophieso genes that influence the risk for autism, hypertension and other

complex traitso the contribution of abnormalities of genes encoding microRNAs to

disorders such as cancero the genetic cause of disorders of skeletal development such as

osteogenesis imperfecta.

All of the IGM investigators also work on developing and evaluating treatments and/or preventative strategies for the disorders that they study, including evaluating blockers of TGF ß signaling as treatment for Marfan syndrome and muscular dystrophies and

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investigating new treatment strategies for sickle cell disease and peroxisomal disorders. In addition to these laboratory activities, several members of the IGM are involved in clinical studies of disease characterization and treatment. The institute also studies issues related to public policy and genetics many of which have great relevance for pediatrics such as stem cell therapy and reproductive testing. The IGM also has a DNA Diagnostic Lab that provides worldwide testing for over 30 genetic disorders that affect children, and it provides training programs for the next generation of pediatric genetic physician scientists.

Hematology

The Division of Pediatric Hematology presently includes five full-time pediatric hematologists, two Ph.D. research scientists and three part-time faculty members. These physicians concentrate solely on benign hematology, as oncology is a separate division. Members of the division have interests in cell motility, platelet surface glycoproteins and alloimmunity, myeloid and mast cell lineage-specific development, coagulation proteins and sickle cell disease. Specific areas of experience and expertise in sickle cell research include induction of fetal hemoglobin to ameliorate the complications of sickle cell disease and the genetics and proteomics of neurovascular disease in sickle cell disease. The division was involved in early studies of the genetic control and pharmacologic manipulation of fetal hemoglobin production, which revolutionized the treatment of sickle cell disease. Several projects are also ongoing in the area of central nervous system damage in sickle cell disease. The Division of Pediatric Hematology is also active in the leadership and conduct of national and international multicenter trials and consortium to study hydroxyurea, treatment of vasoocclusive (painful) crisis and neurologic complications of sickle cell disease. The Division is actively investigating new methods for earlier detection of CNS injury in sickle cell disease, to identify children at risk for neurocognitive impairment and allow earlier treatment. The Divisions of Adult and Pediatric Hematology and Oncology have collaborated on several trials of non-myeloablative bone marrow transplantation for the treatment of sickle cell disease. Proteomic and genetic studies are supported by a large biologic repository that is the by-product of a large multicenter trial of sickle cell disease. The Division has recently been awarded a K12 by the NIH, in conjunction with the Department of Medicine, Division of Hematology, to fund the training of four to six fellows or junior faculty members in benign hematology over the next five years.

Infectious Disease

The Division of Infectious Diseases treats all aspects of infectious diseases and studies pathogens, prevention, transmission and therapy of many pediatric infectious diseases, including bacteria, mycobacteria, parasites and viruses. Its 16 full-time faculty are experts on a wide range of infectious agents, from the viruses and bacteria that cause common respiratory tract infections to the more serious illnesses caused by the Human Immunodeficiency Virus (HIV). A wide variety of interdisciplinary research projects examine issues, such as antibiotic resistance, emerging infections, and the production of

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safe and effective vaccines. The central nervous system (CNS) or brain infection continues to be an important cause of high mortality and morbidity in young infants and children throughout the world, and the research program of the Infectious Disease division has been devoted to the pathogenesis of CNS infection (e.g., bacterial meningitis and cerebral malaria). These researchers are the first to develop the concept that microbial penetration into the brain is the result of specific microbial interactions with the blood-brain barrier. This program has been the major force at both national and international level to advance and promote the research on the CNS infection. The current research program has been taking advantage of advances in microbial genomes to advance knowledge and also develop novel strategies to prevent and treat CNS infections. 

Metabolism

A main interest for this division is to determine how nuclear hormone receptors inhibit gene expression. The regulation of genes that control the thyroid and neuroendocrine feeding axes are investigated using mouse models where nuclear receptors are mutated or deleted in vivo. A related research interest involves study of patients with thyroid hormone resistance and lipodystrophy disorders cause by mutations in nuclear hormone receptor genes. One laboratory focuses on understanding the origin of the pancreatic beta cell absent in patients with diabetes. Researchers are interested in identifying and purifying both mature and progenitor beta cells. Investigators are also interested in the intracellular cAMP signaling pathways that mediate pancreatic beta cell proliferation using a mouse model of constitutively activated nuclear cAMP signaling. This research has the potential to provide novel therapies for patients with type I diabetes mellitus. Investigators are interested in the role of insulin and IGF-1 on the function of the pituitary gonadotroph. These pathways may be an important mediator of GnRH and LH/FSH expression as well as in disorders of the reproduction such as precocious puberty or polycystic ovarian syndrome.

Neonatology

Current research in the Division of Neonatology is organized under three principal themes. The first, genetics of surfactant proteins and human disease, has a lead investigator who is known internationally for identifying various family cohorts with genetic anomalies that are related to Surfactant Protein B and C deficiency that result in chronic lung disease or death. He has recently published pioneering work that, for the first time, shows genetic disorders in a protein that regulates movement of surfactant from inside the synthetic lung cell to the outside. The second major theme is basic laboratory research in developmental neurobiology, which includes: 1) central nervous system injury secondary to hypoxia, 2) adrenergic and adenosine receptor development of the carotid bodies and their effects on control of breathing in development, 3) neurodevelopment of serotonin mechanisms related to autism. Lastly, the third focus, clinical research, largely uses patients who have been cared for in the Johns Hopkins Hospital Neonatal Intensive Care Unit, though patients from other NICUs throughout Baltimore have also been included in specific studies. Recent multicenter NIH sponsored

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studies on managing a blinding eye disease in newborns (Retinopathy of the premature) have been successfully completed. Development and validation of a prognostic neurological exam for premature infants in order to predict long-term outcomes is nearing completion.

Pediatric Outcomes and Policy Research Center

Located on the Johns Hopkins Bayview Medical Center campus, the Center houses a multi-disciplinary collection of 20 faculty from the Johns Hopkins Schools of Medicine, including epidemiologists, health services researchers, biostatisticians, behavioral scientists, nurses, and physicians. The Center also houses data managers and database specialists, public health graduate students, and post-doctoral fellows. They investigate ways to improve the health of children regionally, nationally, and internationally by focusing on clinical outcomes associated with biologic or clinical predisposition for morbidity and mortality and related policies. A critical function of the Center is to provide analytical, statistical and study design support to faculty in the Department of Pediatrics and other investigators in the Children’s Center.

Pulmonary & Cystic Fibrosis

The Johns Hopkins Cystic Fibrosis Clinical and Research Centers include the Pediatric and Adult Clinics, the CF Research and Development Program, the CF Gene Therapy Program Project, the Cystic Fibrosis Therapeutics Development Center and the CF Twin and Sibs Project. These centers have a long history of seminal CF Translational Research. The first clinical trial with AAV serotype 2 vector tgAAVCF was initiated in the Johns Hopkins Pediatric GCRC and demonstrated safety and gene transfer to the right lower lobe of CF lungs. Importantly, the establishment of the gene therapy program later stimulated the development of second generation AAV ad non viral approaches for the treatment of CF. Recently, scientists have identified and successfully tamed an overactive protein that plays a key role in CF. Using RNA interference on cells in the laboratory, researchers successfully intercepted signals sent out by the rampant protein and prevented cell damage by the protein, effectively restoring the cell to normal. The hope is that these findings will be used to design therapies and drugs that go beyond symptom management and actually restore normal cell function to prevent CF. The Division has also piloted the use of computerized data acquisition and standardization of nasal potential difference testing (24) and of sweat rate as two surrogate measures of CFTR function. The Cystic Fibrosis Center at The Johns Hopkins Children’s Center has grown to over 285 pediatric patients. In addition to the faculty who routinely see CF patients in clinic there are 4 other full-time faculty members.

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