Jeffrey Milush, PhD

Dr. Rosenthal is the Director of Pediatric Hepatology, Medical Director of the Pediatric Liver Transplant Program and a Professor of Pediatrics and Surgery at the University of California, San Francisco (UCSF). He is board certified in Pediatrics and Pediatric Gastroenterology and has a Certificate of Added Qualification in Transplant Hepatology. Dr. Rosenthal completed his medical training at Downstate Medical Center and the Albert Einstein Medical Center in New York. He then completed a fellowship in pediatric gastroenterology at UCSF. He joined the UCSF faculty in 1995 after serving as Professor of Pediatrics at University of California, Los Angeles (UCLA). Dr. Rosenthal is a prolific author and a recipient of a number of professional honors and awards and is committed to clinical service, research and education. He has published numerous research articles on hepatitis. Currently, Dr. Rosenthal is pursuing research on the pharmaceutical treatment of hepatitis B and C, genetics and immunology of biliary disease, use of bioartificial liver support utilizing porcine hepatocytes for patients with fulminant liver failure, as well as researching the quality of life following liver transplantation in children. Dr. Rosenthal’s professional services to the public include television, newspaper and radio interviews on various topics such as hepatitis A, B, and C, and liver transplants for local, national and international audiences. He is consultant to organizations such as the American Liver Foundation, Parents of Kids with Infectious Disease, the Centers for Disease Control and Prevention (CDC), and the National Institute of Health (NIH)

Diane Wara, MD, is a professor emeritus of pediatrics in the Allergy/Immunology Bone Marrow Transplant Division, director of the Northern California Pediatric HIV Program, and a member of the leadership group for the NIAID-funded domestic and international clinical trials program in HIV (IMPAACT). Her work, along with that of others, led to the successful strategy for the interruption of perinatal transmission in the developed world. Currently, she is working through IMPAACT to extend and modify successful strategies to prevent transmission throughout the developing world. Dr. Wara has authored more than180 publications and, throughout her career, has focused her research on the pathogenesis and treatment strategies of pediatric immune deficiency syndromes (PIDD) and pediatric HIV. She contributed to reports of the first child with adenosine deaminase deficiency as well as treatment strategies for this disorder, including the successful gene transfer in neonates with known ADA deficiency; the first child with purine nucleoside phosphorylase deficiency; the first child with ZAP-70 deficiency; and mutations in IKK -gamma leading to NEMO syndrome. Dr. Wara contributed to reports of the first child with HIV, the first subject to acquire HIV from a blood transfusion, the first report of vertical transmission of hepatitis C, the role(s) of genetic factors as well as neutralizing antibody in the perinatal transmission of HIV as well as long-term progression; the detection and diagnosis of in-utero versus peripartum transmission. She reported the successful interruption of HIV perinatal transmission by the use of intrapartum AZT to the mother and infant prophylaxis for 6 weeks; she reported numerous successful HIV treatment strategies for children and youth. Dr. Wara led the Immunology Division and the UCSF Pediatric Clinical Research Center for over 25 years. She served as member and chair of two NIH study sections as well as member and chair of the NIH Recombinant DNA Advisory Committee (2002-2006). Dr. Wara was elected to the National Academy of Sciences, Institute of Medicine, in 1998.

OVERVIEW Dr. Valcour is a Professor of Medicine with a shared appointment in the Division of Geriatric Medicine and the Department of Neurology. His work crosses disciplines to research and care for cognitive disorders in aging populations and to understand brain injury in the setting of HIV among all ages, including funded pediatric HIV studies. His clinical work involves consultations for patients with cognitive disorders at the Memory and Aging Center/UCSF. While much of Dr. Valcour's research is completed at UCSF, he has a large internationa porfolio with many opportunities for junior investigators. Within Southeast Asia, he is Deputy Director of SEARCH/Thailand operating research in acute HIV (within days of infection), pediatric HIV, and markers of dementia in chronic HIV. In Africa, he has partnered with the US Military HIV Research Program to survey cognitive disorders among HIV-infected individuals in Nigeria, Uganda, Kenya, and Tanzania. Dr. Valcour is broadly involved in mentoring individuals at all levels of training who are interested in clinical research related to cognitive disorders, particularly in association with HIV infection. He has extensive global health experience. RESEARCH Dr. Valcour’s research interests have two major emphases. He is currently developing a research program that aims to understand optimal care strategies for elders who develop dementia. Nested within the UCSF Memory and Aging Center, the long-term goal of this program is to provide model care for elders with cognitive disorders. Dr. Valcour is internationally recognized for research in cognitive disorders related to HIV. He currently operates 3 NIH R01 series grants within 3 novel cohorts: (1) a chronic HIV infected cohort followed since first initiation of cART; (2) an acute HIV cohort of individuals infected for less than one month at enrollment; (3) and a pediatric cohort in Thailand and Cambodia. He is the Deputy Director of SEARCH/Thailand (www.SEARCHThailand.org). He also operates the UCSF HIV Over 60 Cohort focused on understanding cognitive disorders in the older HIV population living in the San Francisco Bay area. New research will survey of cognitive disorders in HIV for individuals living in Uganda, Kenya, Tanzania and Nigeria. ACADEMIC FOCUS Dr. Valcour is actively engaged in mentoring individuals wishing to become independent clinical researchers. His research portfolio provides a broad array of local and international projects that can serve as resources for mentored projects. Dr. Valcour serves as an Executive Committee member of the AIDS Research Institute (ARI)

Areas of investigation We study processes that result in memory loss and other major neurological deficits, with an emphasis on Alzheimerís disease (AD) and related neurodegenerative disorders. Our long-term goal is to advance the understanding of the healthy and the diseased central nervous system to a point where rational strategies can be developed for the prevention and cure of these conditions. Significance Molecules similar to those involved in neurodegenerative diseases are highly expressed in the nervous system of diverse species and appear to function in learning, synaptic plasticity, and regeneration. We are particularly curious about the roles of amyloid precursor proteins and apolipoprotein E in AD, and a-synuclein in Parkinsonís disease (PD). AD and PD are the most frequent neurodegenerative disorders. They erode peopleís ability to think and control their movements, two of the most critical and intriguing functions of the central nervous system. Both conditions are on the rise and neither can be prevented or cured. These facts underline the significance and urgency of our research efforts. Approaches We use transgenic mouse models and neural cultures to study potential pathogenic factors and pathways at the molecular, cellular, network, and behavioral level. Mouse models are also used to develop and evaluate novel treatment strategies. Their relevance is assessed through comparative studies of humans and postmortem tissues in collaboration with clinical programs. Contributions In AD-related transgenic models, we discovered that amyloid-ß peptides (Aß) can damage synapses and disrupt neural memory circuits independent of their deposition into the visible amyloid plaques that form in AD brains. The plaque-independent toxicity of Aß was inhibited by apolipoprotein E3, but not E4, which may relate to the differential effects of these molecules on AD risk and age of onset. Pathogenic interactions between Aß and a-synuclein worsened cognitive and motor deficits in doubly transgenic mice, a finding of potential relevance to the frequent overlap between AD and PD. Most recently, we discovered that neural network activity in AD-related mouse models fluctuates between abnormal excitation (epilepsy-like) and abnormal inhibition. Remarkably, reducing the protein tau effectively prevented these alterations as well as Aß-induced cognitive deficits. Ongoing studies aim to determine whether such network dysfunction also contributes to cognitive deficits in AD. Some questions addressed in ongoing studies How does Aß affect synaptic function and neuronal survival? How does tau reduction make the brain resistant against Aß-induced deficits? Can the beneficial effect of tau reduction be exploited therapeutically? Which drugs can block the aberrant network activity that Aß triggers? Will these drugs also normalize cognitive functions and prevent neurological decline in AD? What can the selective vulnerability of specific neuronal populations to different neurodegenerative disorders teach us about the uniqueness of the affected cells and the pathogenic cascades involved?