2010 - Jerome Siegel, Ph.D. and Joe Brice Weinberg, M.D.

The 2010 Middleton Award was awarded to two candidates: Jerome Siegel, Ph.D., from the VA Greater Los Angeles Healthcare System, and Joe Brice Weinberg, M.D., from the Durham VA Medical Center.

Jerome Siegel, Ph.D., of the VA Greater Los Angeles Healthcare System was awarded the 2010 William S. Middleton Award in recognition of several areas, including discovering the mechanism of rapid eye movement (REM) sleep, and discovering that the cause of narcolepsy as well as a crucial component of Parkinson's disease is due to loss of hypocretin neurons. Dr. Siegel's work is commendable in its innovativeness and creativity. His methodologies and novel sleep studies resulted in the improved understanding of not only the mechanisms of REM sleep, but also in the very function and evolutionary significance of sleep. This work has resulted in improved treatments for sleep disorders, including the use of hypocretin-1 to treat narcolepsy. His work has had high scientific impact in the treatment of diseases affecting Veterans and patients worldwide.

Joe Brice Weinberg, M.D., of the Durham VA Medical Center was awarded the 2010 William S. Middleton Award in recognition of his contributions to our understanding of resistance to infections, pathways of inflammation, and regulation of normal and leukemic blood cells. His discovery that monocytes can be infected by HIV led to a breakthrough in understanding the pathobiology of the virus. His discovery of the role of nitric oxide and its metabolites in malaria infections led to clinical trials of arginine, which increases NO levels, as a treatment for malaria.

He has been a force of innovation and paradigm change in the field of immunology for the past three decades through his research, leadership and mentorship. Dr. Weinberg's career and scientific contributions has had and will continue to have a high scientific impact in areas involving Veterans and patients worldwide.

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2009 - Michael D. Norenberg, M.D. and Edward Weinman, M.D.

The 2009 Middleton Award was awarded to two candidates: Michael D. Norenberg, M.D., from the VA Miami Healthcare System, and Edward Weinman, M.D., from the VA Maryland Healthcare System in Baltimore.

Michael D. Norenberg, M.D., of the VA Miami Healthcare System was awarded the Williams S. Middleton Award, 2009, for his contributions and understanding that the glial cell biology was an essential part of understanding neurological function and dysfunction. His studies showed that hepatic encephalopathy was primarily a result of astrocyte dysfunction. He alone proved that central pontine myelinosis (CPM) is caused by a rapid correction of hyponatremia (a sodium imbalance), rather than hyponatremia itself. Because of Dr. Norenberg's research and work in this area, he has rapidly transformed the standard therapy for hyponatremia and CPM has consequently become a rarely observed condition in clinical practice today.

Edward Weinman, M.D., of the VA Maryland Healthcare System in Baltimore was awarded the Williams S. Middleton Award, 2009, for his outstanding contribution to our understanding of kidney function, from mapping out the molecular processes to discovering a new family of proteins called NHERF. He showed that these proteins are what regulate kidney functions and demonstrated their function in an animal model. His discovery has impacted not only the clinical relevance of the kidney, but also clinical syndromes in other disparate organ systems such as the gastro-intestinal tract and neurologic systems. Dr. Weinman's scientific contributions will have a widespread impact on the clinical care of Veterans and the general population.

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2008 - Stephen G. Waxman, M.D., Ph.D., West Haven, CT

The 2008 Middleton Award was presented to Stephen G. Waxman, MD, PhD, form the VA Connecticut Healthcare System at West Haven. Dr. Waxman exemplifies the bridge between science and medicine. He has worked in the Dept of Veterans Affairs since 1978. He is the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University, and has served as Chairman of Neurology at Yale since 1986. In 1986, he established the Neuroscience and Regeneration Research Center, a collaboration of the Department of Veterans Affairs, Yale University, and the Paralyzed Veterans of America. Prior to moving to VA Connecticut and Yale, Dr. Waxman worked at Harvard, MIT, and Stanford. He has published more than 500 scientific papers, authored the book Spinal Cord Compression, and has edited eight books. He has trained hundreds of neurologists and neuroscientists. Dr. Waxman's research builds upon the "genomic revolution", to develop new strategies for promoting restoration of function after spinal cord, nerve, and brain injury. His honors include the NIH Tuve Award, the Albert Einstein College of Medicine Distinguished Alumnus Award, and the American Academy of Neurology Dystel Prize and Wartenberg Award, and he is a member of the National Academy of Sciences' Institute of Medicine.

2007 - Robert Freedman, M.D. and Daryl K. Granner, M.D.

The 2007 Middleton Award was awarded to two candidates: Robert Freedman, M.D., from the Denver VAMC, and Daryl K. Granner, M.D. from the Nashville VAMC.

Robert Freedman, M.D., received the 2007 William S. Middleton Award in recognition of his contributions to understanding of the causes and treatment of schizophrenia, a major cause of morbidity in the VA. Not only has he opened doors in our understanding of the role of the nicotinic receptor in P50 gating and schizophrenia, but his paradigm of moving from the molecular neurobiological level, to genetic studies to treatment is a paradigm that has set a precedent for the field. His more recent studies with an alpha-7 nicotinic agonist, DXMB-A hold the potential promise of a new treatment option for schizophrenia distinct from the more conventional approach of the dopamine antagonists. Dr. Freedman's findings have a broad impact on the clinical care of veterans and the population at large.

Dr. Granner was awarded the William S. Middleton Award, 2007, for his discovery of insulin action in diabetes. Dr. Granner was the first to show that insulin regulated gene expression, with a focus on the PEPCK gene. Since this seminal discovery, insulin has been shown to regulate the expression of multiple genes, and is now considered one of the major actions of insulin and important in the development of Type 2 diabetes and other conditions related to Type 2 diabetes. His findings have led to an extension of diabetes related abnormalities to pre-diabetic conditions including the metabolic syndrome, which in turn includes the development of cardiovascular disease in patients who do not have overt diabetes. Dr. Granner's findings have had a broad impact on the clinical care of veterans and the population at large.

2006 - Roland C. Blantz, M.D. and Michael W. Weiner, M.D.

The 2006 Middleton Award was awarded to two candidates- Roland C. Blantz, M.D., from the VA San Diego Healthcare System and Michael W. Weiner, M.D. from the San Francisco VA Medical Center.

Dr. Blantz’s scientific contributions are enormous and include large spectrum of studies related to renal physiology and pathophysiology. He was the first to discover the mechanism by which angiotensin II decreases glomerular filtration, the role of renal nerves and mechanisms of renal regulation through the tubuloglomerular feed back. He is recognized as a world expert in renal physiology and mechanisms of renal disease. His work laid the foundation for clinical studies establishing the role of the renin angiotensin system in progression of renal disease and paved way for new therapeutics. More recently his work has established the link between renal disease and diabetes. He has been a continuously funded VA investigator with national and international reputation.

Dr. Weiner has been a leader in the field of MRI & MRS brain imaging in neurodegenerative disorders for more than two decades. This is an area of high importance in general, as our population ages, as well as to the VA research mission, in particular. In addition, Dr. Weiner has worked in PTSD and Gulf War Illness, both of which have particularly high significance to the VA mission. That Dr. Weiner’s work has emphasized the advancement of neuroimaging is also of high significance. Brain imaging is one of the fastest growing and highest impact areas of research, in close competition with genetics/genomics for overall scientific impact. Dr. Weiner’s work has done a great deal to advance the use of these important techniques in the clinical neurosciences.

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2005 - Thomas D. Bird, M.D

Thomas D. Bird, of the VA Puget Sound Healthcare System, Seattle, WA, was awarded the 2006 Middleton in recognition of his contributions towards our understanding of the genetic bases of neurodegenerative disorders. His work led to the discovery of important genetic mutations involved in major neurodegenerative diseases, notably Alzheimer's Disease (AD) and frontal temporal dementia. The identification of presenilin mutations has been used to create more useful models for AD research, which have proven critical for drug discovery in the amyloid biology field. Dr. Bird's research has also led to discovery of mutations in tau in a subset of frontal temporal dementia. This has also led to the development of animal and cell culture models that, with these mutations, have provided the first, and still the best, models for tangle pathology. With these models, a new arena of drug discovery for AD has been developed. The impact of Dr. Bird's work continues to be substantial and will continue to contribute to the development of new anti-tangle treatments for dementias, a major healthcare problem relevant to the VA as well as the general population.

2004 - John C. Crabbe, Ph.D.

John C. Crabbe, Ph.D., of the Portland VAMC was awarded for his contributions towards our understanding of the genetic bases and behavioral consequences of ethanol intake (e.g., withdrawal and tolerance). His work with animal models of alcoholism has advanced the field of behavioral genetics, and it has important implications for showing the complexity of analogous traits or phenotypes underlying alcohol drinking behavior and alcoholism in humans.

He demonstrated that alcohol tolerance, alcohol dependence and alcohol preference are distinct processes that can be dissected genetically. He has also shown that there is a common genetic mechanism for developing dependence on various drugs of abuse (e.g., alcohol, barbiturates, benzodiapenes and nitrous oxide). His studies have the promise of identifying neural systems affected by protective genes as well as genes that promote risk for development of alcohol and drug dependence. In turn, effective pharmacological and environmental therapies can then be identified for treating addictions.

2003 - Andrew H. Kang, M.D.

Andrew H. Kang, M.D., of the Memphis VAMC was awarded in recognition of his outstanding body of work that continues to impact our understanding and treatment of connective tissue diseases, particularly rheumatoid arthritis. His original and seminal contribution was the discovery and development of the collagen-induced arthritis (CIA) rodent model of chronic arthritis. The CIA model was the first to prove that immunization with an autologous cartilage component could lead to inflammatory, autoimmune arthritis. His work with the animal model also resulted in the development of several potential immunotherapies and vaccines that could prevent the development of CIA. More recently, he has engineered analog peptides that prevent the development of CIA in the animal model. Some of these peptides are currently in clinical trials.

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2002 - Douglas D. Richman, M.D.

Douglas D. Richman, M.D., of VA San Diego Healthcare System was awarded for his research on HIV and AIDS that helped guide treatment for millions of patients worldwide Dr. Richman is noted for his studies on azidothymidine (AZT), the first drug approved in the United States to treat HIV. He and his colleagues established the effectiveness of the drug in the 1980s. Later, studies by Dr. Richman revealed the emergence of AZT-resistant strains of HIV. The appreciation of the importance of HIV drug resistance studies and his pioneering studies on combination drug therapy led to the development in the 1990s of the highly active antiretroviral therapy (HAART). More recently, Dr. Richman has shown that HAART does not completely eradicate HIV, but leaves small reservoirs of HIV in immune cells, even when blood tests show no trace of the virus. Amid these findings, he is at the forefront of efforts to study neutralizing antibodies to HIV, which may be of importance in the development of an AIDS vaccine.

2001 - Eugene C. Butcher, M.D.

Eugene C. Butcher, M.D., of the VA Palo Alto Healthcare System was awarded in recognition of his contributions to the field of immunology, particularly his research on the fundamental processes of immune response and inflammation processes of numerous diseases that affect veterans. Dr. Butcher's work has stimulated and broken new ground in understanding the molecular basis of lymphocyte homing. He identified critical molecules and established the unique homing receptor-ligands for lymphocyte trafficking into and out of the mucosal immune system of the gastrointestinal tract. He also showed that treatment of mice with monoclonal antibodies alpha4 and beta7 block T-cell mediated inflammatory bowel disease, clearly demonstrating the role of these mucosal homing pathways in immunity and inflammation.

1999- Edward R. Block, M.D.

Edward R. Block, M.D., of the Malcolm Randall VA Medical Center in Gainesville, Florida, received the award in recognition of his achievements in the field of pulmonary and critical care medicine. He was among the first to identify and characterize the metabolic functions of lung endothelial cells, leading to a re-evaluation of their role in normal and abnormal lung biology. He subsequently worked on the mechanisms by which oxidant injury affects the metabolic functions of the lung endothelial cells, leading to an understanding of how lung endothelial cell injury leads to acute and chronic manifestations and patho-physiology of lung disease. Dr. Block's work provided the basic science infrastructure for the clinical use of metabolic functions of the lung as indices of pulmonary injury, and for the use of supplemental L-arginine in the treatment of pulmonary vascular dysfunction associated with acute and chronic lung injuries.

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1998 - Robert W. McCarley, M.D.

Robert W. McCarley, M.D., of the Brocton/West Roxbury VA Medical Center was awarded for his contributions to research on sleep and the neurophysiology of behavior. He was the first to systematically develop quantitative to test hypotheses on the cellular control of sleep states. He and his colleagues reported important control mechanisms for the rapid eye movement (REM) state and the non REM state of sleep. These studies set the stage for new approaches to treating sleep abnormalities, including sleep disruptions in psychiatric and other disorders.

Dr. McCarley also made important advances in understanding the basic biology of schizophrenia, a devastating mental illness affecting many veterans. His studies are focused on teasing out brain abnormalities that produce the behavioral symptoms of the disorder.

1997 - Marc A. Schuckit, M.D.

A world leader in the study of alcoholism, Marc A. Schuckit, M.D., of the VA San Diego Healthcare System, was honored for his scientific contributions to the field of alcoholism and drug addiction. Of particular note were his studies showing the importance of genetic influences in alcohol dependence. His innovative population studies set the stage for exciting progress now being made in research to identify genes that play a role in alcoholism. His other major contribution was establishing the relationship between alcohol or drug dependence and severe psychiatric syndromes. He also focused on the treatment of psychiatric problems and the evaluations of the potential importance of separate tracks of care for people dependent on specific types of drugs.

1996 - Daniel Porte, Jr., M.D.

A world-renowned leader in the fields of diabetes and metabolism, Daniel Porte, Jr., M.D., of the Seattle VA Medical Center was honored for his contributions to the field of diabetes. His pivotal observations form the foundation for our current understanding of the neural control of the pancreatic islet cells. He is most recognized for his contributions to our understanding of the role of pancreatic beta-cell dysfunction in the hyperglycemia of non-insulin dependent diabetes. He and his colleagues defined the separate but interactive roles of insulin secretion, insulin sensitivity, and glucose effectiveness in controlling glucose tolerance- all three now recognized to be abnormal in non-insulin dependent diabetes. Dr. Porte was the first to propose that insulin regulates body weight by acting on the brain. He demonstrated the presence of insulin receptors in specific regions of the central nervous system and showed that insulin directly affects neuropeptide y, a potent stimulator of food intake.

1995 - Gerald F. DiBona, M.D.

Gerald F. DiBona, M.D. of the Iowa City VA Medical Center was honored for his internationally recognized contributions to renal and cardiovascular medicine. His research focuses on the neural control of kidney function. He showed that increased nerve activity affected the kidney's ability to filter impurities from the blood, regulate blood flow and control sodium and water retention. As a result, the body retains more sodium and water than normal, and swelling occurs in various parts of the body. Dr. DiBona's work led to the development of possible treatments that work along the entire pathway between the brain and the kidney.

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