Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs California Pacific Medical Research Institute Key CPMCRI Investigators and Clinical Research Programs Approximately 60 principal investigators, both laboratory and clinical researchers, including molecular biologists, immunologists, pharmacologists, biochemists, physicists, epidemiologists, behavioral scientists, biostatisticians, and computer scientists work within the Research Institute and the Medical Center. Biomedical research is conducted in such diverse areas as aging, arthritis, epilepsy, diabetes, neurobiology of pain, cardiovascular disease, osteoporosis, organ transplantation, mechanisms of drug addiction, neurodegenerative diseases (e.g. amyotrophic lateral sclerosis), cancer, AIDS, hepatitis and other infectious diseases. Laboratory Based Research Programs Cancer: Brain Tumors Principal Investigator: Charles Cobbs, M.D. Liliana Soroceanu, M.D., PhD Dr. Cobbs’ laboratory focuses on understanding the molecular mechanisms that lead to the development and progression of malignant gliomas, which are the most lethal form of brain cancer, often killing patients within months of diagnosis. Recent results from Dr. Cobbs’ work have identified the human cytomegalovirus (CMV) in tissue samples from patients with malignant gliomas. While CMV normally causes a common and harmless infection in humans, it may also “push” precancerous cells into an unstable state and thus promote tumor formation. Another example of cancer-promoting viruses comes from the human papilloma virus (HPV) which has been shown to cause cervical cancer. The studies focus on deciphering the pathways that “reactivated” CMV (which may exist dormant within the brain for decades) to drive tumor growth. When the CMV link to cancer is indeed proven, Dr. Cobbs will investigate the possibility of using anti-viral agents for treatment of glioma patients, which would offer new hope for an otherwise devastating disease. Cancer: Culturing Cells for Targeted Breast Cancer Drug Development Principal Investigator: Shanaz Dairkee, PhD In researching life-threatening diseases such as cancer, human experimentation is unethical and impractical. Thus scientists rely heavily on small laboratory-bred animals, mainly mice and rats for testing hypotheses related to the development of cancer, and strategies for its prevention and treatment. Although animal ‘model’ systems have indeed played a key role in advancing our knowledge, due to significant differences in the biology of humans and rodents, improved experimental systems are necessary, wherein the application of new information towards cancer control in patients can be validated. In this regard, getting cancer cells from clinical samples to survive and proliferate outside the body is recognized as a major technical hurdle. This obstacle has been overcome in the Dairkee laboratory by novel approaches, such as simulation of the tumor microenvironment in Petri dishes. Moreover, using genetic engineering techniques, they routinely generate an unlimited supply of patient tumor cells for comprehensive studies. Focusing primarily on human breast cancer cells, detailed molecular analyses are being conducted in the laboratory to Page 1 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs compare them with normal, healthy breast cells from cancer-free individuals as well as between tumors with markedly different degrees of aggressiveness. They anticipate that the characteristics of cultured cancer cells will assist in identifying new approaches for biologically targeted drug development. Their human tumor model systems are also providing information about which drugs work in different types of breast cancer and which don’t, and are therefore a rich testing ground for new, potential pharmacologic therapies. Molecular comparisons of cells in live clinical samples have also facilitated their studies of the very early stages of breast cancer. Here their approach has been to first expose non-cancerous breast cells to known carcinogens and then evaluate whether genetic changes that occur over successive generations reflect those observed in cancerous tissue. It was through studies like this, for example, that they found non-malignant precursor cells that mirror genetic anomalies found in nearby malignant breast cells. In an extension of this work, they are presently studying the biological response of live non-malignant breast cells isolated from women residing in California counties with high breast cancer incidence, to determine whether estrogen-like agents in the environment are a potential risk factor. Among their future goals, an opportunity to apply breakthroughs in breast cancer model system development to other tumor types is a high priority. Cancer: Breast Cancer Disease Progression Principal Investigator: Pierre Desprez, Ph.D. The Desprez research group’s goal is to understand the reasons why some cancers remain localized, and others spread (metastasize), a step of cancer progression generally fatal for cancer patients. This group is particularly interested in breast cancer and they have isolated some important genes (conductor genes) that regulate breast cancer progression to metastasis. They have determined that some of these "conductor genes" can serve as diagnostic as well as prognostic markers for cancer progression in women with breast cancer. In addition, they were also able to inhibit metastasis in preclinical models in the laboratory by blocking the expression of these genes. The lab now focuses on discovering new drugs and reagents that can also block the same genes and therefore the spread of metastatic cancers in human patients. Cancer: Breast Cancer Disease Progression Principal Investigator: John Muschler, Ph.D. In breast cancer the cells grow as disorganized masses, attachment process is often absent, and growth control is not regulated. Specific molecular information on breast cell attachment is one potential key to controlling disease progression, and even for finding ways to prevent breast cancer. Dr. Muschler recently discovered that a molecule called "dystroglycan" (DG) is important for cell attachment and signaling growth arrest in breast cells. It appears that dystroglycan is non-functional in the majority of breast tumor cells. Most importantly, introducing dystroglycan function into breast cancer cells can restore many normal properties. In the early stages of breast cancer, there is considerable evidence that restoring critical attachment function will serve to reverse the disease. Evidence indicates that loss of DG function is one part of cancer progression. Nothing is currently known about how dystroglycan functions in normal breast cells and how its function is undermined in cancer cells. Dr. Muschler’s lab Page 2 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs studies: (i) how dystroglycan acts in normal breast cells; and (ii) which functions of DG are critical to activate its tumor suppressor function. The long-term aim of this study is to understand how dystroglycan function is undermined in tumor cells, and identify methods to restore DG function to these cells. Cancer: Cancer and Cannabinoids Principal Investigator: Sean McAllister, PhD We have discovered that non-psychotropic cannabinoid constituents, of the plant Cannabis sativa, can inhibit the growth of and kill aggressive human breast cancer cells in culture. These compounds can also inhibit the properties of breast cancer cells that allow them to spread to other parts of the body (i.e., they can inhibit metastatic properties). An anticancer agent with a low toxicity profile that can both inhibit cancer cell growth and metastasis would be extremely valuable clinically. Cannabinoid compounds have a low toxicity profile and have been demonstrated to inhibit a broad range of human cancers. Dr. McAllister’s laboratory is currently determining the mechanism(s) by which cannabinoids interact with aggressive breast and brain cancer cells to produce thier anticancer activity. Understanding the mechanisms behind the anticancer activity of cannabinoids may also lead to the discovery of a new biological target for the development of diagnostic tools and additional therapies for the treatment of cancer. Cancer: Drug Development of Novel Compounds for Improved Treatment Principal Investigator: Li-xi Yang, M.D. Metastatic cancers, particularly breast and lung, represent an ongoing treatment challenge. Currently available standard chemotherapeutic drugs have limited effectiveness on metastatic tumors and carry significant toxicity for patients. Dr. Yang’s laboratory investigates the therapeutic properties/action at the cellular level of current chemotherapeutic drugs, with the goal of altering their composition to develop a second generation drug that may provide a drug with enhanced effectiveness and less toxicity. Cancer: Complementary Medicine Principal Investigator: Garret Yount, Ph.D. Dr. Garret Yount is exploring how promising complementary and alternative medical therapies might be integrated with conventional medicine in the treatment of patients with cancer. His laboratory applies state-of-the-art molecular biology tools to assess the efficacy of Chinese herbs and Qigong under rigorously controlled experimental conditions. Another focus of Dr. Yount’s laboratory is the invasive behaviors of cancer cells. Using time-lapse microscopy, he recently discovered that fragments of cancer cells are able to pinch off from the cell body and migrate independently. He is exploring whether these independent tumor cell fragments will prove useful as effective delivery systems for gene therapies because of their ability to mimic tumor cell migration. Cancer: Gene Therapy Principal Investigator: Robert Debs, MD Page 3 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs Despite all currently-available therapies, the great majority of patients who develop metastatic cancer still die from their disease. Over the last 20 years, it has become clear that the development of specific genetic abnormalities produce cancers and other common fatal human diseases. Although our understanding of the genetic causes of human cancer has improved dramatically, the inability to correct these underlying genetic abnormalities in patients has prevented the development of truly safe and effective therapies for cancer and other genetic diseases. The research in my laboratory focuses on the development of safe and effective methods that specifically correct abnormal, cancer-causing genes directly in patients. The gene therapy approaches we are developing would, if successful, effectively treat a broad range of human diseases, including cancer, heart diseases, infectious diseases and neurodegenerative diseases. Several prior approaches developed in the Debs laboratory have already been translated into gene therapy trials in human patients with cystic fibrosis or with metastatic cancer. Earlier, an approach developed in his laboratory led directly to the development of the second drug approved by the FDA for use in AIDS patients, and the first therapy that prolonged life in these patients. Cancer: Melanoma Principal Investigator: Mohammed Kashani-Sabet, MD Malignant melanoma is the fifth most common malignancy in the United States, and its incidence is increasingly more rapidly than any other cancer. Dr. Kashani utilizes a large patient data set for analysis of diagnostic and prognostic factors for patients with melanoma and cutaneous lymphoma to test novel molecular diagnostic and prognostic factors derived from various laboratory-based analyses that may either yield independent information regarding diagnosis or prognosis or that may explain the basis of known factors, such as ulceration and vascular invasion. Understanding the relative impact of such histologic and molecular factors will result in homogeneous patient groups from which to base treatment decisions, possibly resulting in different treatment algorithms from those currently in use. Cell Biology Principal Investigator: Giuseppe Inesi, MD, PhD Dr Inesi's laboratory is engaged in a long term research project on Cardiac Molecular and Cell Biology. This research will clarify the mechanism involved in transport of calcium across cell membranes, as well as the involvement of these proteins in cardiac failure. Disturbances of calcium distribution in heart muscle cells is one of the main causes of heart attack and weakened heart muscle. This research is also contributing to our understanding of how calcium blocking cardiac drugs work, and will open up the way to development of new pharmacological agents to treat heart disease. Neurobiology of Disease Principal Investigator: Dmitri Leonoudakis, PhD During the aging process, molecular and biochemical changes in the brain lead to impairments in cognitive and motor function and are major risk factors for neurological disorders such as Alzheimer disease (AD) and Parkinson disease (PD). The Leonoudakis laboratory is testing the hypothesis that Page 4 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs dystroglycan (DG) function is altered during aging where it contributes to neuroinflammation, neurodegeneration and cognitive decline. Loss of functional DG may allow leakage of inflammatory factors into the brain substance. Other studies in the laboratory have shown that the postinjury inflammatory response in the brain produces excitotoxicity by excessive signaling in nerve cells mediated by the inflammatory cytokine tumor necrosis factors. Immunology: Infection/Host Response and Liver/Pancreas Biorepository Principal Investigator: Stewart Cooper, MD The research aim of Stewart Cooper, MD, MRCP, sounds straightforward enough. “We want to establish the mechanisms of protective immunity against hepatitis C virus infection,” he says. “If we understand the type of immune response leading to spontaneous clearance of virus, then we can figure out which part of the immune system to stimulate in order to achieve protective vaccination.” While this overall research goal has not changed much in 20 years, Cooper is now taking some new paths to reach that goal. In this next phase of his research, he is directing a new basic liver research program at California Pacific Medical Center Research Institute Cooper is now laying the groundwork for several innovative studies to track actual human immune responses to initial HCV infection. Page 5 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs Clinical Research Programs San Francisco Coordinating Center Director: Steven Cummings, MD CPMRI Investigators: Peggy Cawthon, PhD , Katie Stone PhD, Gregory Tranah PhD, Esther Wei, ScD, Warren Browner MD, MPH The San Francisco Coordinating Center uniquely combines scientific expertise with broad experience in managing multi-center studies, and offers access to a network of high quality, experienced clinical centers. The mission of the SFCC is to conduct novel clinical research that sets new standards for excellence and efficiency. A joint venture between CPMCRI and UCSF, the SFCC works selectively with industry and NIH to develop and conduct studies that have a critical impact on clinical research and public health. CPMCRI’s investigators at the SFCC are extraordinarily prolific, with more than 40 scientific papers in 2010 alone. Areas of ongoing research at SFCC include women’s health, aging/longevity, cognitive function/dementia, cardiovascular disease, breast cancer prevention, colon cancer screening and prevention, osteoporosis, arthritis, endocrine disorders, insomnia/sleep disorders, genetics, neonatology, and research methods in biostatistics and study design. Breast Health Study and San Francisco Mammography Registry Principal Investigator: Steven Cummings, MD Project Leader: Alice LaRocca The Breast Health Study is compiling a databank of mammograms and blood samples that, in combination with new technologies, may help clinicians predict postmenopausal women's risk of developing breast cancer. All of this will eventually allow clinicians to see if combinations of a women's breast density, age, family history, hormone levels, and genetics will give us an accurate assessment of her breast cancer risk. Compounds have become available that may reduce a woman's risk of developing breast cancer by as much as 70 percent, so it will be critical to develop a personalized medicine approach to identify which patients may benefit and what treatment they should receive. Roughly 45,000 CPMC patients per year have had breast-density mammograms since 2005 and more than 20,000 have given blood samples. Cardiology: Principal Investigators: Richard Shaw, PhD and Ernest Haeusslein, MD Dr. Shaw’s research focuses on the impact of treatment guidelines on quality of care, risk reduction strategies, and analysis of large datasets to determine risk predictions for different interventions. In addition to heart transplant research, Dr. Haeusslein studies pharmacological and mechanical circulatory device therapies to improve end-stage heart disease management. Gastroenterology: Interventional Endoscopy Principal Investigators: Kenneth Binmoeller, MD, Janek Shah, MD and Antonio Quiros, MD Interventional endoscopy allows the gastroenterologist to not only diagnose, but to perform surgical procedures. A channel within the endoscope provides a conduit to introduce miniature instruments Page 6 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs for the endoscopist's use during examination and procedures. Miniature endoscopes can be passed through the channel enabling endoscopic procedures in the bile and pancreatic ducts. Tiny ultrasound transducers are even used to examine tiny lesions within the gastrointestinal tract. Drs. Binmoeller and Shah have been on the forefront of clinical research as the first endoscopists to research and clinically utilize many of the new micro-instruments for detecting and treating disorders. Examples of device clinical trials they have embarked upon include: tissue sampling devices (brush, forceps and aspiration needles), needle and wire “knives,” injection catheters, clip, band, suture, and stent applicators, thermal coagulation probes, balloons and baskets, miniature endoscopes, and miniature ultrasound catheters. Gastroenterology: Neurogastroenterology and Motility Disorders Principal Investigators: William Snape, MD and Katerina Shetler, MD Approximately 35 million Americans suffer from gastrointestinal motility disorders. These disorders range from gastroparesis, affecting a small number each year, to common gastrointestinal disorders irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and fecal incontinence. Motility disorders can involve any part of the gastrointestinal (GI) tract including the esophagus, stomach, small intestines and colon. Dr. Snape is the Principal Investigator of a nation-wide, federally funded study with the National Institutes of Diabetes and Digestion and Kidney Diseases. The Gastroparesis Registry (GpR) is an observational study to clarify the epidemiology, natural history, clinical course, and other outcomes of gastroparesis. The Gastroparesis Registry will also provide a resource to inform the development of clinical trials and ancillary studies of the epidemiology, etiology, pathophysiology, and impact of gastroparesis . Clinical studies By Drs. Snape and Shetler are already underway which focus on nausea, diabetes control, aspiration risk after extubation, and pharmalogical interventions. Gastroenterology: Pediatric Principal Investigator: Antonio Quiros, MD Dr. Quiros has an active pediatric research program, examining the immunology, genetic predictors, and treatment of pediatric inflammatory bowel diseases, and the use of endoscopic devices. Mind-Body Medicine Principal Investigators: John Astin, PhD and Cassandra Vieten, PhD Drs Astin and Vieten's research sutdies how the mind and its attendant thoughts, feelings, psychological constructs, and levels of stress can impact our physical health. They are studying the potential value of meditation-based interventions to help prevent relapse from addictive disorders. In this work, they are testing the theory that by developing the capacity for greater mindfulness, i.e., the ability to attend to one's present moment experience (thoughts, feelings, sensations, circumstances) with greater openness and acceptance and in turn less habitual reactivity and judgment, then recovering addicts will be better able to manage distressing emotional states and thereby lessen their Page 7 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs habitual tendency to use drugs or alcohol to manage and cope with those powerful emotions or thoughts when they arise. Other research tests the potential value of mindfulness-based interventions to reduce stress and negative affect during pregnancy. A large body of data has linked stress during pregnancy to a host of negative outcomes including greater likelihood of complications during labor and delivery; higher incidence of post-partum depression; and impaired fetal/infant development. Drs Vieten and Astin are examining if mindfulness-based interventions can help ameliorate or prevent some of these problems from occurring. Dr. Astin, in collaboration with CPMCRI Scientific Director Michael Rowbotham, is studying how to improve the informed consent process for enrolling participants in human research studies. An ongoing study compares an interactive consent form presented on an iPad using technology developed by CPMCRI’s Dr. Steven Cummings with the traditional paper-based method. Neuroscience: Forbes Norris MDA/ALS Research and Treatment Center Principal Investigators: Robert Miller, MD, Jonathan Katz, MD and Susan Woolley-Levin, PhD Drs. Miller and Katz have an international reputation for their leadership in studies of potential therapies for amyotrophic lateral sclerosis (Lou Gehrig’s Disease). The Forbes Norris MDA/ALS Research and Treatment Center at CPMC has been a part of essentially every significant study of how to treat ALS conducted over the past 15 years, including the recent studies of lithium for ALS. Dr. Miller and Dr. Katz are active in many ALS research consortia: CPMC is one of five hub sites for the MDA-ALS consortium; CPMC is the western regional leader for PAC-10; Dr. Katz is President of the ALS Research Group; and CPMC is also active in the Northeast ALS Consortium and the Western ALS Group. Neuropsychologist Dr. Susan Woolley-Levin is part of the NINDS-funded Common Data Elements research project for ALS. The CPMC group is active on research into other neuromuscular diseases, such as myasthenia gravis and muscular dystrophy. Dr. Katz has a particular interest in peripheral neuropathies and is part of GBS/CIDP International; CPMC is one of 15 centers in the USA. This group has completed several national collaborative projects focused on immune neuropathy outcomes and criteria. At any one time as many as a dozen studies are enrolling subjects, with funding from the NIH, the Muscular Dystrophy Association, and industry. Neuroscience: Sutter Pacific Epilepsy Program Principal Investigators: Kenneth Laxer, MD, David King-Stephens, MD and Peter Weber, MD Dr. Laxer has been involved in epilepsy research since the early 1970’s, playing an active role in the development of neuroimaging techniques for the evaluation of epilepsy, surgical and non-surgical temporal lobe epilepsy treatment, and vagus nerve stimulation for seizure control. Together with Drs. King-Stephens and Weber, the Sutter Pacific Epilepsy Program maintains a comprehensive research program with 13 active approved protocols ranging from studies of neuromodulation devices, new anti-epileptic drugs, and brain pathology in patients with epilepsy. Neuroscience: Pain Clinical Research Principal Investigator: Michael Rowbotham, MD Dr. Rowbotham’s research primarily focuses on chronic neuropathic pain, the pain that follows injury to the peripheral or central nervous system. Current areas of interest include research into the clinical Page 8 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs mechanisms underlying painful peripheral neuropathy from cancer chemotherapy, pain following ‘shingles’ (herpes zoster and post-herpetic neuralgia), and the transition from acute to chronic pain. Dr. Rowbotham is also actively involved in the design and conduct of large scale clinical trials of new analgesics. Dr. Rowbotham plays a leadership role in national and international clinical research and education initiatives, such as the ACTTION public-private partnership that brings together the FDA, NIH, academic investigators, and industry to accelerate treatment development by improving clinical trials. Neuroscience: CPMC Center for Stroke Research Principal Investigators: David Tong, MD, Jack Rose, MD, Jeffrey Thomas MD, and Nobl Barazangi, MD Dr. Tong’s work as an early leader in applying telemedicine to rapid evaluation and treatment of patients with acute stroke has led to CPMC being a hub site for an NSA-funded telestroke trial, Advancing Telestroke Care (ATC). Dr. David Tong of CPMC is on the board of the Western States Stroke Consortium; collaborative projects are a goal of this consortium. Dr. Thomas is involved in several studies of neurovascular interventions such as stents and other vascular reconstruction devices. As part of the NINDS-funded national NETT (Neurological Emergency Treatment Trials) program, Dr. Barazangi has lead CPMC’s participation in several important studies of seizure and stroke management, such as RAMPART, POINT, and ALIAS. In addition, she and the rest of CPMC’s stroke group have been involved in industry-sponsored trials of new therapies. Most recently, Dr. Barazangi initiated a pilot study of her own design (PERFUSE; with support from SPMF and CPMCRI) examining ways to extend the time window for patients with acute stroke to receive rTPA. Oncology Principal Investigators: Ari Baron, MD, Kathleen Grant, MD, Kevin Knopf, MD, Allan Kramer, MD, David Minor, MD, Bert Tuan, MD, and Wei Wang, MD, PhD Oncology clinical research at CPMCRI is robust, offering cancer patients entry into pharmaceutical and biotech sponsored clinical trials as well as National Cancer Institute clinical trials. An oncologist may be selected to be the Principal Investigator of the study and the others may be listed as co-investigators. This means all oncologists may enroll into any open study at any time. Oncologists may enroll into any NCI clinical trial once they have received certification from the NCI and consortiums to allow participation. Dr. Minor is the Principal Investigator for the majority of melanoma clinical trials conducted at CPMC. The melanoma clinical trials complement the basic science research conducted by Dr. Kashani and the surgical expertise of Drs. Leong and Singer. Combined, this team represents a comprehensive melanoma program at CPMC. Dr. Minor is an expert in melanoma and a knowledge leader for the recently approved FDA drug, ipilimumab. He has conducted phase 1 to pivotal phase 3 clinical trials of ipilimumab and has published extensively in this area. Dr. Minor and Dr. Wang are working with industry sponsors to move emerging therapies targeting specific genetic mutations into trials for treating treat melanoma patients. These studies are entering the critical phase 3 process providing additional optimism for advanced melanoma patients. Page 9 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs Dr. Baron is the Principal Investigators on numerous clinical trials at CPMC. He has a special interest in prostate cancer. In the past years, he has focused on prostate cancer of numerous Phase 2 and 3 studies. Participation in these studies has resulted in FDA approval for cabazitaxel (2010) and abiraterone acetate (2011). As these drugs are approved, he continues to conduct clinical trials as our industry sponsors work to fine tune dosing and minimize symptoms of newly approved drugs. He also works with industry sponsors to identify new compounds for clinical research. Dr. Baron is also the Principal Investigator for cancers of the colon, breast, lung, pancreas, and liver. Working with surgeons and physicians at CPMC and in the Bay Area, the Oncologists receive numerous referrals and upon consenting and qualification will enter patients into clinical trials suitable for their disease. The oncologists work towards establishing a variety of clinical trials for each stage of disease treatment. Pharmacology: Addiction & Pharmacology Research Laboratory (APRL) Principal Investigators: Gantt Galloway, PharmD and John Mendelson, MD The disease of addiction is produced by interactions between individual biological organisms (people), specific pharmacological agents (drugs), and the social, economic, cultural, biologic, and geographic milieu (environment). The Addiction Pharmacology Research Laboratory is dedicated to understanding how specific pharmacologic compounds (drugs) contribute to developing or treating addictive disease. We believe that deciphering the biological effects of drugs is essential for developing effective therapies to treat addiction. We exist to conduct human research on the effects of addictive and abused drugs and to develop new medications and treatments for drug addiction. We are dedicated to the safe and ethical human study of addictive and abused drugs, both in controlled laboratory settings and in people living and functioning in the community. Ongoing research has a special focus on Methamphetamine and MDMA (Ecstasy) abuse. Transplant Program: Kidney Transplant Principal Investigators: Ram Peddi, MD, Parul Patel, MD, and Kimi Ueda, PharmD Kidney transplant research is integrated into patient care at CPMC. All patients listed for a transplant are aware of the research program through receipt of research information from the research team and conversations with the transplant nephrologists regarding clinical trials. Clinical trials may be conducting in the operating room, immediately post-transplant while hospitalized, or several weeks or months later to combat a graft-threatening virus. The majority of trials seek to improve transplantation outcomes with better drug treatments. This team regularly prepares abstracts and publishes manuscripts to describe innovations, observations and clinical trials they conduct. Transplant Program: Liver Transplant and Hepatology Principal Investigators: Maurizio Bonacini MD, Natalie Bzowej MD, PhD, Timothy Davern MD, Todd Frederick MD, Jennifer Guy MD, Raphael Merriman MD, and Adil Wakil, MD The Liver Disease Management and Transplant Program promotes clinical research into clinical care. Areas of research interest include hepatitis B and C disease management, hepatoma, hepatitis and HIV co-infection, nonalcoholic steatohepatitis, hepatorenal syndrome, pre and post-liver transplant and Page 10 of 11 Updated July 2011 Appendix A: Thumbnail Sketches of Key CPMCRI Investigators and Clinical Research Programs other complex liver diseases. After conducting both Phase 2 and pivotal phase 3 clinical trials, Dr. Bzowej has recently received recognition with the recently FDA approved hepatitis C virus drug, telaprevir. which lead to FDA approval. In addition to HCV clinical trials, Dr. Bzowej is a Principal Investigator for a National Institute of Diabetes and Digestion and Kidney Diseases (NIDDK) trial entitled, the Hepatitis B Research Network (HBRN). The purpose of this national network is to describe participants with hepatitis B virus (HBV) infection and identify factors that may cause the disease to activate or worsen. Dr. Jennifer Guy studies hepatocellular cancer, which is often associated with chronic viral hepatitis. Dr. Davern is a nationally-recognized expert on acute liver injury. He is the Principal Investigator of two NIDDK clinical trials. One is the Drug Induced Liver Injury Network (DILIN). An objective of DILIN is to develop standardized definitions and instruments to identify and fully characterize cases of druginduced liver injury. With a systematic way of classifying drug-induced liver injury, to enable the analysis, epidemiology and clinical issues of liver injury and collect biological samples that can be used to study the causes of liver toxicity using biochemical, serological, and genetic testing. Another objective of DILIN is to establish a registry of patients who have experienced severe drug induced liver injury. His second trial funded by the NIDDK is entitled, the Study of N-Acetylcysteine in Acute Liver Failure (ALF). The purpose of this multi-center open label study is to determine if N-acetylcysteine has any survival benefits in patients with ALF. Dr. Maurizio Bonacini is co-Investigator on the DILIN Network grant and is an active investigator in the area of HIV-associated liver disease. Dr. Merriman also has received funding from the NIDDK to enroll patients into the Nonalcoholic Fatty Liver Disease (NAFLD) Adult Database 2. The NAFLD Database 2 will recruit at least 600 new adult participants suspected or known to have NAFLD or NASH-related cirrhosis. The purpose of this study is to elucidate, through the cooperative effort of a multidisciplinary and multicenter group of collaborators, the etiology, natural history, diagnosis, treatment, and prevention of NAFLD, and in particular its more severe form of NASH and its complications. Page 11 of 11 Updated July 2011